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Síndrome linfoproliferativo autoimune
ORPHA:3261CID-10 · D47.9CID-11 · 4A01.22DOENÇA RARA

A Síndrome Linfoproliferativa Autoimune (ALPS) é uma doença rara e genética. Ela se caracteriza por uma multiplicação de células de defesa (linfócitos) que não é câncer, pela diminuição de vários tipos de células do sangue e por um risco aumentado, ao longo da vida, de desenvolver linfomas (tipos de câncer do sistema linfático), como os linfomas de Hodgkin e não Hodgkin.

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Introdução

O que você precisa saber de cara

📋

A Síndrome Linfoproliferativa Autoimune (ALPS) é uma doença rara e genética. Ela se caracteriza por uma multiplicação de células de defesa (linfócitos) que não é câncer, pela diminuição de vários tipos de células do sangue e por um risco aumentado, ao longo da vida, de desenvolver linfomas (tipos de câncer do sistema linfático), como os linfomas de Hodgkin e não Hodgkin.

Pesquisas ativas
4 ensaios
17 total registrados no ClinicalTrials.gov
Publicações científicas
631 artigos
Último publicado: 2026 Mar 18

Escala de raridade

CLASSIFICAÇÃO ORPHANET · BRASIL 2024
Unknown
Ultra-rara
<1/50k
Muito rara
1/20k
Rara
1/10k
Pouco freq.
1/5k
Incomum
1/2k
Prevalência
0.0
Worldwide
Casos conhecidos
500
pacientes catalogados
Início
All ages
🏥
SUS: Sem cobertura SUSScore: 0%
CID-10: D47.9
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Sinais e sintomas

O que aparece no corpo e com que frequência cada sintoma acontece

Partes do corpo afetadas

🩸
Sangue
29 sintomas
🫁
Pulmão
10 sintomas
🫃
Digestivo
10 sintomas
🫘
Rins
7 sintomas
🧬
Pele e cabelo
6 sintomas
📏
Crescimento
6 sintomas

+ 83 sintomas em outras categorias

Características mais comuns

90%prev.
Linfadenopatia crônica não infecciosa
Muito frequente (99-80%)
90%prev.
Linfadenopatia
Muito frequente (99-80%)
90%prev.
Esplenomegalia
Muito frequente (99-80%)
90%prev.
Autoimunidade
Muito frequente (99-80%)
55%prev.
Aumento da concentração circulante de interleucina 10
Frequente (79-30%)
55%prev.
Apoptose linfocitária anormal
Frequente (79-30%)
173sintomas
Muito frequente (4)
Frequente (14)
Ocasional (31)
Muito raro (23)
Sem dados (101)

Os sintomas variam de pessoa para pessoa. Abaixo estão as 173 características clínicas mais associadas, ordenadas por frequência.

Linfadenopatia crônica não infecciosaChronic noninfectious lymphadenopathy
Muito frequente (99-80%)90%
LinfadenopatiaLymphadenopathy
Muito frequente (99-80%)90%
EsplenomegaliaSplenomegaly
Muito frequente (99-80%)90%
AutoimunidadeAutoimmunity
Muito frequente (99-80%)90%
Aumento da concentração circulante de interleucina 10Increased circulating interleukin 10 concentration
Frequente (79-30%)55%

Linha do tempo da pesquisa

Publicações por ano — veja quando o interesse científico cresceu
Anos de pesquisa1desde 2026
Total histórico631PubMed
Últimos 10 anos200publicações
Pico202242 papers
Linha do tempo
2026Hoje · 2026🧪 1993Primeiro ensaio clínico📈 2022Ano de pico
Publicações por ano (últimos 10 anos)

Encontrou um erro ou informação desatualizada? Sugira uma correção →

Genética e causas

O que está alterado no DNA e como passa nas famílias

Genes associados

8 genes identificados com associação a esta condição. Padrão de herança: Autosomal dominant, Autosomal recessive.

FASTumor necrosis factor receptor superfamily member 6Disease-causing somatic mutation(s) inAltamente restrito
FUNÇÃO

Receptor for TNFSF6/FASLG. The adapter molecule FADD recruits caspase CASP8 to the activated receptor. The resulting death-inducing signaling complex (DISC) performs CASP8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate-specific cysteine proteases) mediating apoptosis. FAS-mediated apoptosis may have a role in the induction of peripheral tolerance, in the antigen-stimulated suicide of mature T-cells, or both. The secreted isoforms 2 to 6 block apoptosis (in v

LOCALIZAÇÃO

Cell membraneMembrane raftSecreted

VIAS BIOLÓGICAS (7)
RIPK1-mediated regulated necrosisCASP8 activity is inhibitedRegulation by c-FLIPCaspase activation via Death Receptors in the presence of ligandDimerization of procaspase-8
MECANISMO DE DOENÇA

Autoimmune lymphoproliferative syndrome 1A

A disorder of apoptosis that manifests in early childhood and results in the accumulation of autoreactive lymphocytes. It is characterized by non-malignant lymphadenopathy with hepatosplenomegaly, and autoimmune hemolytic anemia, thrombocytopenia and neutropenia.

EXPRESSÃO TECIDUAL(Ubíquo)
Linfócitos
75.4 TPM
Ovário
43.2 TPM
Fibroblastos
41.0 TPM
Pulmão
37.9 TPM
Cervix Endocervix
28.8 TPM
OUTRAS DOENÇAS (4)
autoimmune lymphoproliferative syndrome type 1Vogt-Koyanagi-Harada diseaseBehcet diseaseautoimmune lymphoproliferative syndrome
HGNC:11920UniProt:P25445
KRASGTPase KRasDisease-causing germline mutation(s) inAltamente restrito
FUNÇÃO

Ras proteins bind GDP/GTP and possess intrinsic GTPase activity (PubMed:20949621, PubMed:39809765). Plays an important role in the regulation of cell proliferation (PubMed:22711838, PubMed:23698361). Activates MAPK1/MAPK3 resulting in phosphorylation and ultimately degradation of GJA1 (By similarity). Plays a role in promoting oncogenic events by inducing transcriptional silencing of tumor suppressor genes (TSGs) in colorectal cancer (CRC) cells in a ZNF304-dependent manner (PubMed:24623306)

LOCALIZAÇÃO

Cell membraneEndomembrane systemCytoplasm, cytosol

VIAS BIOLÓGICAS (2)
Signaling by moderate kinase activity BRAF mutantsRUNX3 regulates p14-ARF
MECANISMO DE DOENÇA

Leukemia, acute myelogenous

A subtype of acute leukemia, a cancer of the white blood cells. AML is a malignant disease of bone marrow characterized by maturational arrest of hematopoietic precursors at an early stage of development. Clonal expansion of myeloid blasts occurs in bone marrow, blood, and other tissue. Myelogenous leukemias develop from changes in cells that normally produce neutrophils, basophils, eosinophils and monocytes.

EXPRESSÃO TECIDUAL(Ubíquo)
Nervo tibial
30.7 TPM
Cérebro - Hemisfério cerebelar
25.1 TPM
Esôfago - Muscular
22.2 TPM
Esôfago - Mucosa
21.6 TPM
Esôfago - Junção
20.2 TPM
OUTRAS DOENÇAS (20)
gastric canceracute myeloid leukemialinear nevus sebaceous syndromeNoonan syndrome 3
HGNC:6407UniProt:P01116
PRKCDProtein kinase C delta typeDisease-causing germline mutation(s) inAltamente restrito
FUNÇÃO

Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays contrasting roles in cell death and cell survival by functioning as a pro-apoptotic protein during DNA damage-induced apoptosis, but acting as an anti-apoptotic protein during cytokine receptor-initiated cell death, is involved in tumor suppression as well as survival of several cancers, is required for oxygen radical production by NADPH oxidase and acts as positive or negative regula

LOCALIZAÇÃO

CytoplasmCytoplasm, perinuclear regionNucleusCell membraneMitochondrionEndomembrane system

VIAS BIOLÓGICAS (9)
Interferon gamma signalingApoptotic cleavage of cellular proteinsVEGFR2 mediated cell proliferationRole of phospholipids in phagocytosisDAG and IP3 signaling
MECANISMO DE DOENÇA

Autoimmune lymphoproliferative syndrome 3

A primary immunodeficiency characterized by antibody deficiency, hypogammaglobulinemia, recurrent bacterial infections and an inability to mount an antibody response to antigen. The defect results from a failure of B-cell differentiation and impaired secretion of immunoglobulins; the numbers of circulating B-cells is usually in the normal range, but can be low. CVID9 patients have B-cell deficiency and severe autoimmunity.

EXPRESSÃO TECIDUAL(Ubíquo)
Sangue
133.8 TPM
Linfócitos
106.4 TPM
Baço
82.6 TPM
Tireoide
81.7 TPM
Pulmão
73.4 TPM
OUTRAS DOENÇAS (1)
autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD
HGNC:9399UniProt:Q05655
CASP8Caspase-8Disease-causing germline mutation(s) inTolerante
FUNÇÃO

Thiol protease that plays a key role in programmed cell death by acting as a molecular switch for apoptosis, necroptosis and pyroptosis, and is required to prevent tissue damage during embryonic development and adulthood (PubMed:23516580, PubMed:35338844, PubMed:35446120, PubMed:8681376, PubMed:8681377, PubMed:8962078, PubMed:9006941, PubMed:9184224). Initiator protease that induces extrinsic apoptosis by mediating cleavage and activation of effector caspases responsible for FAS/CD95-mediated an

LOCALIZAÇÃO

CytoplasmNucleusCell projection, lamellipodium

VIAS BIOLÓGICAS (10)
NOD1/2 Signaling PathwayNF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10Caspase activation via Death Receptors in the presence of ligandDimerization of procaspase-8TRIF-mediated programmed cell death
MECANISMO DE DOENÇA

Caspase-8 deficiency

Disorder resembling autoimmune lymphoproliferative syndrome (ALPS). It is characterized by lymphadenopathy, splenomegaly, and defective CD95-induced apoptosis of peripheral blood lymphocytes (PBLs). It leads to defects in activation of T-lymphocytes, B-lymphocytes, and natural killer cells leading to immunodeficiency characterized by recurrent sinopulmonary and herpes simplex virus infections and poor responses to immunization.

OUTRAS DOENÇAS (5)
hepatocellular carcinomaautoimmune lymphoproliferative syndrome type 2Badult hepatocellular carcinomahereditary breast carcinoma
HGNC:1509UniProt:Q14790
NRASGTPase NRasDisease-causing germline mutation(s) inAltamente restrito
FUNÇÃO

Ras proteins bind GDP/GTP and possess intrinsic GTPase activity

LOCALIZAÇÃO

Cell membraneGolgi apparatus membrane

VIAS BIOLÓGICAS (2)
Signaling by moderate kinase activity BRAF mutantsNeutrophil degranulation
MECANISMO DE DOENÇA

Leukemia, juvenile myelomonocytic

An aggressive pediatric myelodysplastic syndrome/myeloproliferative disorder characterized by malignant transformation in the hematopoietic stem cell compartment with proliferation of differentiated progeny. Patients have splenomegaly, enlarged lymph nodes, rashes, and hemorrhages.

EXPRESSÃO TECIDUAL(Ubíquo)
Linfócitos
77.3 TPM
Fibroblastos
52.5 TPM
Skin Not Sun Exposed Suprapubic
25.1 TPM
Esôfago - Mucosa
24.4 TPM
Skin Sun Exposed Lower leg
23.4 TPM
OUTRAS DOENÇAS (13)
neurocutaneous melanocytosislarge congenital melanocytic nevusthyroid cancer, nonmedullary, 2colorectal cancer
HGNC:7989UniProt:P01111
CTLA4Cytotoxic T-lymphocyte protein 4Disease-causing germline mutation(s) inAltamente restrito
FUNÇÃO

Inhibitory receptor acting as a major negative regulator of T-cell responses (PubMed:11279501, PubMed:11279502, PubMed:16551244, PubMed:1714933, PubMed:18641304, PubMed:28484017). Acts as a decoy receptor: the affinity of CTLA4 for its natural B7 family ligands, CD80 and CD86, is considerably stronger than the affinity of their cognate stimulatory coreceptor CD28 (PubMed:11279501, PubMed:11279502, PubMed:16551244, PubMed:1714933, PubMed:28484017)

LOCALIZAÇÃO

Cell membrane

VIAS BIOLÓGICAS (3)
Co-stimulation by CD28Co-inhibition by CTLA4RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs)
MECANISMO DE DOENÇA

Systemic lupus erythematosus

A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow.

EXPRESSÃO TECIDUAL(Tecido-específico)
Baço
5.8 TPM
Intestino delgado
4.9 TPM
Pulmão
4.3 TPM
Testículo
2.5 TPM
Sangue
1.8 TPM
OUTRAS DOENÇAS (6)
autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiencysystemic lupus erythematosusgranulomatosis with polyangiitismycosis fungoides
HGNC:2505UniProt:P16410
CASP10Caspase-10Disease-causing germline mutation(s) inTolerante
FUNÇÃO

Involved in the activation cascade of caspases responsible for apoptosis execution. Recruited to both Fas- and TNFR-1 receptors in a FADD dependent manner. May participate in the granzyme B apoptotic pathways. Cleaves and activates effector caspases CASP3, CASP4, CASP6, CASP7, CASP8 and CASP9. Hydrolyzes the small- molecule substrates, Tyr-Val-Ala-Asp-|-AMC and Asp-Glu-Val-Asp-|-AMC Isoform 7 can enhance NF-kappaB activity but promotes only slight apoptosis Isoform C is proteolytically inactive

LOCALIZAÇÃO

VIAS BIOLÓGICAS (4)
NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10TP53 Regulates Transcription of Caspase Activators and CaspasesTRAIL signalingFasL/ CD95L signaling
MECANISMO DE DOENÇA

Autoimmune lymphoproliferative syndrome 2A

A disorder of apoptosis that manifests in early childhood and results in the accumulation of autoreactive lymphocytes. It is characterized by non-malignant lymphadenopathy with hepatosplenomegaly, and autoimmune hemolytic anemia, thrombocytopenia and neutropenia.

OUTRAS DOENÇAS (4)
lymphoma, non-Hodgkin, familialgastric cancerautoimmune lymphoproliferative syndrome type 2Aautoimmune lymphoproliferative syndrome
HGNC:1500UniProt:Q92851
FASLGTumor necrosis factor ligand superfamily member 6Disease-causing germline mutation(s) inRestrito
FUNÇÃO

Cytokine that binds to TNFRSF6/FAS, a receptor that transduces the apoptotic signal into cells (PubMed:26334989, PubMed:9228058). Involved in cytotoxic T-cell-mediated apoptosis, natural killer cell-mediated apoptosis and in T-cell development (PubMed:7528780, PubMed:9228058, PubMed:9427603). Initiates fratricidal/suicidal activation-induced cell death (AICD) in antigen-activated T-cells contributing to the termination of immune responses (By similarity). TNFRSF6/FAS-mediated apoptosis also has

LOCALIZAÇÃO

Cell membraneCytoplasmic vesicle lumenLysosome lumenSecretedNucleus

VIAS BIOLÓGICAS (9)
RIPK1-mediated regulated necrosisCASP8 activity is inhibitedRegulation by c-FLIPCaspase activation via Death Receptors in the presence of ligandDimerization of procaspase-8
MECANISMO DE DOENÇA

Autoimmune lymphoproliferative syndrome 1B

A disorder of apoptosis that manifests in early childhood and results in the accumulation of autoreactive lymphocytes. It is characterized by non-malignant lymphadenopathy with hepatosplenomegaly, and autoimmune hemolytic anemia, thrombocytopenia and neutropenia.

EXPRESSÃO TECIDUAL(Tecido-específico)
Baço
5.8 TPM
Sangue
1.7 TPM
Pulmão
1.5 TPM
Intestino delgado
0.7 TPM
Fallopian Tube
0.5 TPM
OUTRAS DOENÇAS (3)
autoimmune lymphoproliferative syndrome type 1autoimmune lymphoproliferative syndromelung cancer
HGNC:11936UniProt:P48023

Variantes genéticas (ClinVar)

729 variantes patogênicas registradas no ClinVar.

🧬 FAS: NM_000043.6(FAS):c.197-11T>G ()
🧬 FAS: NM_000043.6(FAS):c.293C>T (p.Ser98Phe) ()
🧬 FAS: NM_000043.6(FAS):c.569-16T>G ()
🧬 FAS: NM_000043.6(FAS):c.329G>A (p.Gly110Glu) ()
🧬 FAS: NM_000043.6(FAS):c.443+2T>C ()
Ver todas no ClinVar

Classificação de variantes (ClinVar)

Distribuição de 2,418 variantes classificadas pelo ClinVar.

121
846
1451
Patogênica (5.0%)
VUS (35.0%)
Benigna (60.0%)
VARIANTES MAIS SIGNIFICATIVAS
CASP8: NM_001372051.1(CASP8):c.613dup (p.Val205fs) [Pathogenic]
LOC129936895: NM_006254.4(PRKCD):c.352G>C (p.Val118Leu) [Uncertain significance]
PRKCD: NM_006254.4(PRKCD):c.25T>C (p.Phe9Leu) [Uncertain significance]
FASLG: NM_000639.3(FASLG):c.737G>A (p.Gly246Glu) [Uncertain significance]
FASLG: NM_000639.3(FASLG):c.821C>T (p.Thr274Met) [Uncertain significance]

Vias biológicas (Reactome)

72 vias biológicas associadas aos genes desta condição.

Caspase activation via Death Receptors in the presence of ligand Regulation by c-FLIP RIPK1-mediated regulated necrosis CASP8 activity is inhibited TP53 Regulates Transcription of Death Receptors and Ligands Dimerization of procaspase-8 FasL/ CD95L signaling SOS-mediated signalling Activation of RAS in B cells Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants SHC1 events in ERBB2 signaling SHC1 events in ERBB4 signaling Signaling by SCF-KIT Signalling to RAS p38MAPK events GRB2 events in EGFR signaling SHC1 events in EGFR signaling Downstream signal transduction GRB2 events in ERBB2 signaling Tie2 Signaling EGFR Transactivation by Gastrin DAP12 signaling SHC-related events triggered by IGF1R FCERI mediated MAPK activation NCAM signaling for neurite out-growth Ca2+ pathway Ras activation upon Ca2+ influx through NMDA receptor VEGFR2 mediated cell proliferation CD209 (DC-SIGN) signaling Constitutive Signaling by EGFRvIII SHC-mediated cascade:FGFR1 FRS-mediated FGFR1 signaling SHC-mediated cascade:FGFR2 FRS-mediated FGFR2 signaling SHC-mediated cascade:FGFR3 FRS-mediated FGFR3 signaling FRS-mediated FGFR4 signaling Apoptotic cleavage of cellular proteins Calmodulin induced events Effects of PIP2 hydrolysis DAG and IP3 signaling Role of phospholipids in phagocytosis G alpha (z) signalling events HuR (ELAVL1) binds and stabilizes mRNA CLEC7A (Dectin-1) signaling RHO GTPases Activate NADPH Oxidases Neutrophil degranulation Interferon gamma signaling KEAP1-NFE2L2 pathway NOD1/2 Signaling Pathway TRIF-mediated programmed cell death Caspase-mediated cleavage of cytoskeletal proteins TNFR1-induced proapoptotic signaling Regulation of TNFR1 signaling CLEC7A/inflammasome pathway Regulation of necroptotic cell death Activation, myristolyation of BID and translocation to mitochondria Apoptotic execution phase TRAIL signaling TLR3-mediated TICAM1-dependent programmed cell death NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10 Microbial modulation of RIPK1-mediated regulated necrosis Defective RIPK1-mediated regulated necrosis Regulation of NF-kappa B signaling SHC-mediated cascade:FGFR4 Co-stimulation by CD28 Co-inhibition by CTLA4 RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs) TP53 Regulates Transcription of Caspase Activators and Caspases Interleukin-4 and Interleukin-13 signaling Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models FOXO-mediated transcription of cell death genes

Diagnóstico

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Tratamento e manejo

Remédios, cuidados de apoio e o que precisa acompanhar

Pipeline de tratamentos
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·Pré-clínico3
Medicamentos catalogadosEnsaios clínicos· 0 medicamentos · 6 ensaios
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Onde tratar no SUS

Hospitais de referência no Brasil e o protocolo oficial do SUS (PCDT)

🇧🇷 Atendimento SUS — Síndrome linfoproliferativo autoimune

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Selecione um estado ou use sua localização para ver resultados.

Dados de DATASUS/CNES, SBGM, ABNeuro e Ministério da Saúde. Sempre confirme a disponibilidade diretamente com o estabelecimento.

Pesquisa ativa

Ensaios clínicos abertos e novidades científicas recentes

🟢 Recrutando agora

3 pesquisas recrutando participantes. Converse com seu médico sobre a possibilidade de participar.

Outros ensaios clínicos

17 ensaios clínicos encontrados, 4 ativos.

Distribuição por fase
Ver todos no ClinicalTrials.gov
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Publicações mais relevantes

Timeline de publicações
312 papers (10 anos)
#1

Childhood isolated C3d-positive AIHA: favorable prognosis but rare relapse or associated immunodeficiency.

Blood advances2026 Jan 27

Autoimmune hemolytic anemia (AIHA) with an isolated C3d+ direct antiglobulin test is a rare and understudied condition in children. It typically encompasses cold agglutinin syndrome and paroxysmal cold hemoglobinuria, both transient, infection-triggered disorders collectively referred to as cold AIHA. We report a national cohort of 142 pediatric patients with isolated C3d+ AIHA, representing 21.6% of all childhood AIHA cases enrolled in the French OBS'CEREVANCE cohort over a 32-year period. The median age at diagnosis was 3.2 years (male-to-female ratio, 1.3), and median follow-up was 2.8 years. Infectious symptoms were present in 63.4% of cases. At diagnosis, median hemoglobin was 6.4 g/dL; 69.7% of patients had inadequate reticulocytosis (bone marrow responsiveness index of <121), and 90.4% required transfusions. Eighteen patients (12.7%) had or developed immunopathological manifestations (IM) including 5 diagnosed with primary immunodeficiency (4 with autoimmune lymphoproliferative syndrome). Among 8 (5.6%) patients with relapsing disease, 6 had no IM at diagnosis but 4 developed IM at relapse. Nine patients were antinuclear antibodies (ANA) positive; none progressed to systemic lupus over a median follow-up of 4.9 years. Corticosteroids were administered to 82.4% of patients (median duration, 4.5 months), with no clear benefit over untreated patients regarding hospital stay or transfusion needs. No deaths were reported. In conclusion, pediatric isolated C3d+ AIHA generally follows a favorable course. However, a minority of patients may reveal underlying immune disorders, highlighting the importance of tailored evaluation at diagnosis. Cold agglutinin testing with thermal amplitude and Donath-Landsteiner testing, rarely performed in this cohort, warrant further study for their impact on diagnosis and clinical management.

#2

Lymphoproliferation in Inborn Errors of Immunity: Mechanisms, Manifestations and Clinical Management, with a Focus on ALPID.

ImmunoTargets and therapy2026

Lymphoproliferation represents a common and clinically relevant feature across many Inborn Errors of Immunity (IEIs), reflecting the underlying immune dysregulation that characterizes these disorders. In affected individuals, lymphoproliferation may manifest along a broad clinical spectrum, ranging from benign forms such as lymphadenopathy, splenomegaly, and hepatomegaly to malignant transformation, including lymphoma and leukemia. Multiple and heterogeneous pathogenetic mechanisms contribute to lymphoproliferation in IEIs; however, they can be conceptually grouped into two major categories: excessive lymphocyte activation and proliferation, and defective control of proliferation. The association of lymphoproliferation with autoimmune cytopenia classically defined the Autoimmune Lymphoproliferative Syndrome (ALPS), caused by an impairment in FAS-mediated apoptosis. However, a growing number of IEIs present with overlapping autoimmune lymphoproliferative phenotypes driven by diverse monogenic defects or, in many cases, without an identifiable genetic cause. This expanding spectrum has led to the concept of autoimmune lymphoproliferative immunodeficiencies (ALPID), encompassing a continuum of disorders characterized by lymphoproliferation, autoimmunity and diverse genetic backgrounds, requiring disease-specific therapeutic approaches. This narrative review provides an overview of the main IEIs associated with lymphoproliferation focusing on pathogenic pathways, diagnostic evaluation and classification, and current and emerging targeted therapeutic approaches.

#3

Monogenic Neonatal Diabetes: Clinical Presentations, Genetic Findings, and Response to Therapy in a Retrospective Case Series.

Cureus2026 Jan

Introduction Monogenic neonatal diabetes mellitus (NDM) is a rare form of diabetes, presenting within the first six months of life and caused by pathogenic variants affecting pancreatic β-cell development or function. Because its initial presentation may overlap with type 1 diabetes, molecular diagnosis is crucial, as it directly influences prognosis and treatment - particularly the potential responsiveness to sulfonylureas in ATP-sensitive potassium (KATP)-channel-related NDM. This study reports a retrospective descriptive case series and aims to characterize the clinical and genetic features of infants with NDM, to improve therapeutic management and long-term outcomes. Materials and methods We conducted a retrospective descriptive case series of infants diagnosed with diabetes before six months of age, hospitalized in the Pediatric Endocrinology Unit of the Abderrahim Harouchi Mother-Child Hospital, Casablanca, Morocco, between January 2018 and December 2025. Clinical presentation, biochemical data, insulin requirements, genetic results, and outcomes were extracted from medical records. Genetic testing was performed through next-generation sequencing (NGS), or targeted Sanger sequencing when financially feasible. Results Ten infants were included (nine males and one female), with a mean age at diagnosis of 71 days. Diabetic ketoacidosis (DKA) was the presenting feature in all cases. Consanguinity was reported in 55% of families. Pathogenic or likely pathogenic variants were identified in six infants (60%), involving ABCC8, INS, EIF2AK3, CASP10, and chromosome 6q23-24 duplication, including two syndromic forms. Two infants with ABCC8 mutations achieved insulin independence with sulfonylurea therapy. Syndromic etiologies - Wolcott-Rallison syndrome, Donohue syndrome, and autoimmune lymphoproliferative syndrome type IIA (ALPS-type IIA) - were associated with severe multisystemic involvement. Three children had no identifiable pathogenic variant, despite clinical features consistent with NDM. Long-term outcomes varied widely, ranging from normal neurodevelopment to early mortality in Donohue syndrome. Conclusion This retrospective descriptive case series highlights the marked genetic heterogeneity and clinical variability of neonatal diabetes in a resource-limited setting. Genetic testing enabled precision therapy in infants harboring KATP-channel mutations and clarified prognosis in syndromic forms. Expanding access to molecular diagnostics remains essential to improve equity in care, optimize metabolic outcomes, and support individualized management strategies.

#4

Long-Term Outcomes of Successful Treatment with Ruxolitinib in a Pediatric Patient with Autoimmune Lymphoproliferative Syndrome and a Signal Transducer and Activator of Transcription 3 Gain-of-Function Mutation.

Klinische Padiatrie2026 Feb 27

Loss or gain-of-function mutations in signal transducer and transcription activator genes, classified as combined immunodeficiency, can present with highly heterogeneous and life-threatening clinical presentations. We report an adolescent girl who has combined immunodeficiency associated with signal transducer and activator of transcription 3 gain-of-function, c.1032G > C, p.Met344Ile located in exon 10, identified by a next-generation sequencing panel performed due to short stature, hepatosplenomegaly, and decreased levels of both immunoglobulin G and immunoglobulin M. At 12 years of age, the patient was referred to the pediatric hematology outpatient clinic owing to hepatosplenomegaly and pancytopenia after initiating growth hormone treatment due to short stature. On physical examination, bilateral multiple posterior and anterior cervical micro-lymphadenopathies were detected, her liver was palpated 6 cm below the costal margin, and her spleen was palpated 10 cm below the costalmargin. The whole blood count revealed a leukocyte count of 2,300/mm3, neutrophils of 1,330/mm3, lymphocytes of 730/mm3, hemoglobin of 8 g/dL, platelets of 96,000/mm3, and reticulocytes of 2%. The bone marrow biopsy revealed a cellularity of 30-35%. After steroid-dependent treatment resulted in Cushing syndrome and treatment with sirolimus was ineffective, treatment with ruxolitinib 20 mg twice daily significantly resolved cytopenias and hepatosplenomegaly due to autoimmune lymphoproliferative syndrome. Funktionsverlust- oder Funktionsgewinnmutationen in Signaltransduktor- und Transkriptionsaktivator-(STAT)-Genen, die als kombinierte Immundefekte klassifiziert werden, können sich mit sehr heterogenen und lebensbedrohlichen klinischen Manifestationen manifestieren. Wir berichten über ein jugendliches Mädchen mit einer STAT3-Funktionsgewinnmutation (GOF), c.1032G>C, p.Met344Ile in Exon 10, die mittels Next-Generation-Sequenzierung (NGS) identifiziert wurde. Die Untersuchung wurde aufgrund von Kleinwuchs, Hepatosplenomegalie, erniedrigten Immunglobulin-G- und Immunglobulin-M-Spiegeln durchgeführt. Im Alter von 12 Jahren wurde die Patientin aufgrund von Hepatosplenomegalie und Panzytopenie, die nach Beginn einer Wachstumshormontherapie aufgrund des Kleinwuchses auftraten, in die pädiatrische Hämatologie-Ambulanz überwiesen. Bei der körperlichen Untersuchung wurden beidseitig multiple zervikale Mikrolymphadenopathien, posteriore und anteriore, festgestellt. Die Leber war 6 cm und die Milz 10 cm unterhalb des Rippenbogens tastbar. Das Blutbild zeigte folgende Werte: Leukozyten 2300/mm³, Neutrophile 1330/mm³, Lymphozyten 730/mm³, Hämoglobin 8 g/dl, Thrombozyten 96 000/mm³ und Retikulozyten 2 %. Die Knochenmarkbiopsie ergab eine Zellularität von 30–35 %. Nach einer vorangegangenen steroidabhängigen Behandlung, die zu einem Cushing-Syndrom und einem Nichtansprechen auf Sirolimus führte, besserten sich die Zytopenien und die Hepatosplenomegalie signifikant unter der zweimal täglichen Gabe von 20 mg Ruxolitinib aufgrund eines autoimmunen lymphoproliferativen Syndroms (ALPS).

#5

CASP8 and CASP3 mRNA Expression in Autoimmune Lymphoproliferative Syndrome (ALPS) and Chronic Immune Thrombocytopenia (ITP).

Genes2026 Feb 09

Fas/FasL-mediated apoptosis is central to immune homeostasis and is implicated in autoimmune lymphoproliferative syndrome (ALPS) and immune thrombocytopenia (ITP). We aimed to compare whole-blood transcriptional levels of CASP8 and CASP3 across ALPS, chronic ITP, and healthy controls. CASP8 and CASP3 mRNA expression was quantified by real-time PCR in whole blood from clinically diagnosed ALPS patients, chronic ITP patients, and healthy controls. CASP8 mRNA expression was significantly increased in ALPS and ITP versus controls (p = 0.0009 and p < 0.0001, respectively) and was lower in ALPS than in ITP (p = 0.0265). CASP3 mRNA was also increased in both patient groups versus controls (ALPS: p = 0.0045; ITP: p < 0.0001), with no significant difference between ALPS and ITP (p = 0.1692). ALPS and chronic ITP show distinct CASP8 transcriptional patterns and a shared upregulation of CASP3 at the whole-blood mRNA level. These findings are descriptive and do not directly assess caspase activation or apoptotic pathway activity; further protein- and cell subset-based studies are needed to clarify functional implications.

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2026

A curated list of immune system associated genes related to cancer.

BMC genomic data
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Lymphoproliferation in Inborn Errors of Immunity: Mechanisms, Manifestations and Clinical Management, with a Focus on ALPID.

ImmunoTargets and therapy
2026

Monogenic Neonatal Diabetes: Clinical Presentations, Genetic Findings, and Response to Therapy in a Retrospective Case Series.

Cureus
2026

Long-Term Outcomes of Successful Treatment with Ruxolitinib in a Pediatric Patient with Autoimmune Lymphoproliferative Syndrome and a Signal Transducer and Activator of Transcription 3 Gain-of-Function Mutation.

Klinische Padiatrie
2026

CASP8 and CASP3 mRNA Expression in Autoimmune Lymphoproliferative Syndrome (ALPS) and Chronic Immune Thrombocytopenia (ITP).

Genes
2026

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Journal of veterinary internal medicine
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Autoimmune lymphoproliferative syndrome in Boerboel dogs: clinicopathologic, diagnostic, and genetic characterization.

Journal of veterinary internal medicine
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Lipid Nanoparticle Fas Gene Therapy Suppresses Autoimmune Lymphoproliferative Syndrome in Mice.

Blood immunology &amp; cellular therapy
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Targeted deep sequencing identifies mosaicism in patients with immune dysregulation.

The Journal of allergy and clinical immunology
2026

Leniolisib reduced lymphoproliferative disease in murine autoimmune lymphoproliferative syndrome.

Journal of human immunity
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Genetic Testing in Patients With Autoimmune Lymphoproliferative Syndrome: Experience of 802 Patients at Cincinnati Children's Hospital Medical Center.

Pediatrics
2025

DHHC21 is a STIM1 protein S-acyltransferase that modulates immune function in vivo.

bioRxiv : the preprint server for biology
2026

Challenges in diagnosis and management of pulmonary valve endocarditis associated with autoimmune lymphoproliferative syndrome (ALPS): A case report and literature review.

Radiology case reports
2026

Childhood isolated C3d-positive AIHA: favorable prognosis but rare relapse or associated immunodeficiency.

Blood advances
2025

Diffuse Large B-cell lymphoma in a Ras-Associated Autoimmune Leukoproliferative Disorder (RALD).

Annals of hematology
2026

Lessons from the American College of Allergy, Asthma and Immunology inborn errors of immunity survey: Advancing diagnostic and therapeutic strategies for the practicing allergist-immunologist.

Annals of allergy, asthma &amp; immunology : official publication of the American College of Allergy, Asthma, &amp; Immunology
2025

A Novel Cause of CIDP: Homozygous Hotspot Mutation, c.793 C > T in CASP8 Gene.

Journal of clinical immunology
2025

Malignancy and Autoimmune Susceptibility in Adult Patients with Human Inborn Errors of Immunity.

Journal of clinical immunology
2025

Long-term management of recurrent uveitis associated with autoimmune lymphoproliferative syndrome.

Journal of ophthalmic inflammation and infection
2025

[Progress in diagnosis and treatment of RAS-related autoimmune lymphoproliferative disorder].

Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics
2025

Case Report: FAS spontaneous mutation in a familial hemophagocytic lymphohistiocytosis patient with a complex heterozygous mutation in PRF1.

Frontiers in immunology
2025

Effectiveness of sirolimus for early on-set autoimmune cytopenias of autoimmune lymphoproliferative immunodeficiencies.

Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology
2025

T-Cell Receptor CRαβ+CD4-CD8- (Double-Negative) T Cells May Predict Pathological Kidney Findings in Patients with Suspected Lupus Nephritis.

Nephron
2025

Case Report: Clinical, molecular, and functional characterization of autoimmune lymphoproliferative syndrome-a family study with a multimodal diagnosis.

Frontiers in pediatrics
2025

Atypical lymphoproliferations associated with germline genetic variants: a report of the 2024 EA4HP/SH lymphoma workshop.

Virchows Archiv : an international journal of pathology
2025

Clinical features and novel pathogenic variants of patients with Behçet's disease like trisomy 8.

Orphanet journal of rare diseases
2025

Inborn errors of immunity presenting with lymphoproliferation: lessons from a case series.

Annals of hematology
2025

Inborn Errors of Immunity in Apoptosis.

Frontiers in bioscience (Landmark edition)
2024

FDG PET Scan in Cutaneous Rosai-Dorfman-Destombes Disease.

Indian journal of nuclear medicine : IJNM : the official journal of the Society of Nuclear Medicine, India
2025

Heterozygous germline TET2 loss-of-function variants associated with an ALPS-like phenotype.

British journal of haematology
2025

The Fas-mediated apoptosis assay: From concept to clinical application.

Journal of immunological methods
2025

RASGRP1 Deficiency Associated with Diffuse Mesangial Sclerosis Infantile Nephrotic Syndrome and Epstein-Barr Virus-Induced Hodgkin's Lymphoma.

Pediatric allergy, immunology, and pulmonology
2025

Impact of Anti-CD4 Autoantibodies on Immune Reconstitution in People With Advanced HIV.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
2024

Beyond FAScinating: advances in diagnosis and management of autoimmune lymphoproliferative syndrome and activated PI3 kinase δ syndrome.

Hematology. American Society of Hematology. Education Program
2024

Nonspecific increase of αβTCR+ double-negative T cells in pediatric rheumatic diseases.

World journal of pediatrics : WJP
2024

Functional role of UNC13D in immune diseases and its therapeutic applications.

Frontiers in immunology
2024

Novel Compound Heterozygous Variants in the FAS Gene Lead to Fetal Onset of Autoimmune Lymphoproliferative Syndrome (ALPS).

Journal of clinical immunology
2024

Wiskott-Aldrich Syndrome: A Report of a Rare X-Linked Disorder.

Cureus
2024

Revisiting double-negative T cells in autoimmune lymphoproliferative immunodeficiencies: a case series.

Allergologia et immunopathologia
2024

Double-negative T cells in pediatric rheumatic diseases.

Clinical and experimental pediatrics
2025

A Rare Case of Retinal Vasculitis in a Patient With Autoimmune Lymphoproliferative Syndrome.

Ophthalmic surgery, lasers &amp; imaging retina
2024

Disseminated Macrolide-Resistant Mycobacterium intracellulare Infection in a Child with Autoimmune Lymphoproliferative Disorder: A Case Report and Literature Review.

The American journal of tropical medicine and hygiene
2024

Flow cytometry-based diagnostic approach for inborn errors of immunity: experience from Algeria.

Frontiers in immunology
2024

[Primary immunodeficiency disease based on ITK mutation: report of a case].

Zhonghua bing li xue za zhi = Chinese journal of pathology
2024

Infection risk in patients with autoimmune cytopenias and immune dysregulation treated with mycophenolate mofetil and sirolimus.

Frontiers in immunology
2024

Ras-associated autoimmune lymphoproliferative disorder.

British journal of haematology
2024

The Etiologic Landscape of Lymphoproliferation in Childhood: Proposal for a Diagnostic Approach Exploring from Infections to Inborn Errors of Immunity and Metabolic Diseases.

Therapeutics and clinical risk management
2024

Study of the potential role of CASPASE-10 mutations in the development of autoimmune lymphoproliferative syndrome.

Cell death &amp; disease
2024

Looking for ALPS: The value of a combined assessment of biochemical markers.

Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology
2024

Unveiling the Uncommon: A Unique Case of ALPS-like Syndrome Complicated by Plasma Cell Disorder.

Journal of pediatric hematology/oncology
2024

Monoallelic KRAS (G13C) mutation triggers dysregulated expansion in induced pluripotent stem cell-derived hematopoietic progenitor cells.

Stem cell research &amp; therapy
2024

Infections in Disorders of Immune Regulation.

Pathogens (Basel, Switzerland)
2024

Detection of signature double-negative T cells is a predictive marker to identify autoimmune lymphoproliferative syndrome associated with FAS loss of function.

American journal of hematology
2024

Probable Autoimmune Lymphoproliferative Syndrome with Monogenic Lupus Due to KRAS Mutation.

Mediterranean journal of hematology and infectious diseases
2024

Validation of Artificial Intelligence (AI)-Assisted Flow Cytometry Analysis for Immunological Disorders.

Diagnostics (Basel, Switzerland)
2024

Enrichment of Immune Dysregulation Disorders in Adult Patients with Human Inborn Errors of Immunity.

Journal of clinical immunology
2024

Diagnostic evaluation of paediatric autoimmune lymphoproliferative immunodeficiencies (ALPID): a prospective cohort study.

The Lancet. Haematology
2024

Double-Negative T (DNT) Cells in Patients with Systemic Lupus Erythematosus.

Biomedicines
2024

Non-apoptotic FAS signaling controls mTOR activation and extrafollicular maturation in human B cells.

Science immunology
2023

Opinion paper: effectiveness of sirolimus in treating partial Di George syndrome with autoimmune lymphoproliferative syndrome-like features.

Frontiers in pediatrics
2023

Late-Onset Autoimmune Lymphoproliferative Syndrome in a Costa Rican Woman.

Cureus
2024

A case of autoimmune lymphoproliferative syndrome with a novel de novo FAS variant.

Pediatric hematology and oncology
2024

Abnormal biomarkers predict complex FAS or FADD defects missed by exome sequencing.

The Journal of allergy and clinical immunology
2024

Autoimmune lymphoproliferative immunodeficiencies (ALPIDs): A proposed approach to redefining ALPS and other lymphoproliferative immune disorders.

The Journal of allergy and clinical immunology
2023

Characterizing the regulatory Fas (CD95) epitope critical for agonist antibody targeting and CAR-T bystander function in ovarian cancer.

Cell death and differentiation
2023

Understanding the Spectrum of Immune Dysregulation Manifestations in Autoimmune Lymphoproliferative Syndrome and Autoimmune Lymphoproliferative Syndrome-like Disorders.

Rheumatic diseases clinics of North America
2023

Guardians of Immunity: Advances in Primary Immunodeficiency Disorders and Management.

Cureus
2023

Phenotypic Variability in PRKCD: a Review of the Literature.

Journal of clinical immunology
2024

Combined germline and somatic human FADD mutations cause autoimmune lymphoproliferative syndrome.

The Journal of allergy and clinical immunology
2024

Bilateral Panuveitis in an Adolescent with Autoimmune Lymphoproliferative Syndrome Due to CTLA4 Haploinsufficiency.

Ocular immunology and inflammation
2023

Autoimmune lymphoproliferative immunodeficiencies (ALPID) in childhood: breakdown of immune homeostasis and immune dysregulation.

Molecular and cellular pediatrics
2023

Autoimmune lymphoproliferative syndrome: A disorder of immune dysregulation.

Autoimmunity reviews
2023

Severe RAS-Associated Lymphoproliferative Disease Case with Increasing αβ Double-Negative T Cells with Atypical Features.

Journal of clinical immunology
2023

The role of caspase-8 in inflammatory signalling and pyroptotic cell death.

Seminars in immunology
2023

Summer rain and wet soil rather than management affect the distribution of a toxic plant in production grasslands.

Scientific reports
2024

Autoimmune lymphoproliferative syndrome (ALPS) due to a novel dominant negative germline mutation in the FAS gene.

Immunologic research
2023

The impact of Treosulfan-based conditioning for inborn errors of immunity: Is dose monitoring crucial?

Clinical transplantation
2023

Cutaneous Eruption Associated with Sirolimus in a Child with FAS-Associated Autoimmune Lymphoproliferative Syndrome.

Journal of clinical immunology
2023

Ecodatacube.eu: analysis-ready open environmental data cube for Europe.

PeerJ
2023

Expanding the clinical phenotype of FADD deficiency with a novel mutation and its role in Fas-mediated apoptotic pathway.

British journal of haematology
2023

Case report: Neonatal autoimmune lymphoproliferative syndrome with a novel pathogenic homozygous FAS variant effectively treated with sirolimus.

Frontiers in pediatrics
2023

Chai Disease Mimicking Autoimmune Lymphoproliferative Syndrome.

Indian journal of pediatrics
2023

Case report: Synergistic defects of CASP10 and BTK leading to autoimmune lymphoproliferative syndrome type IIa, complicated by severe hemophagocytic lymphohistiocytosis.

Immunologic research
2023

Severe autoimmune lymphoproliferative syndrome phenotype in a pediatric patient with a germline FAS gene variant.

Pediatric blood &amp; cancer
2023

Autoimmune Lymphoproliferative Syndrome (ALPS) Disease and ALPS Phenotype: Are They Two Distinct Entities?

HemaSphere
2023

Clinical, immunologic, and genetic characteristics of children with ALPS: A single-center experience.

Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology
2022

Autoimmune lymphoproliferative syndrome identified through reverse phenotyping.

Central-European journal of immunology
2022

Case report: Effectiveness of sirolimus in treating partial DiGeorge Syndrome with Autoimmune Lymphoproliferative Syndrome (ALPS)-like features.

Frontiers in pediatrics
2023

Revisiting autoimmune lymphoproliferative syndrome caused by Fas ligand mutations.

The Journal of allergy and clinical immunology
2022

Unusual Polyclonal IgM in an IgG Deficient Patient with Autoimmune Lymphoproliferative Syndrome: A Case Study and Literature Review.

Annals of clinical and laboratory science
2022

[Autoimmune lymphoproliferative syndrome: a case report].

The Pan African medical journal
2022

Detection and evolutionary dynamics of somatic FAS variants in autoimmune lymphoproliferative syndrome: Diagnostic implications.

Frontiers in immunology
2022

Rosai-Dorfman Disease between Proliferation and Neoplasia.

Cancers
2022

P2X7 purinergic receptor plays a critical role in maintaining T-cell homeostasis and preventing lupus pathogenesis.

Frontiers in immunology
2022

Eosinophilic gastrointestinal disorders in patients with inborn errors of immunity: Data from the USIDNET registry.

Frontiers in immunology
2022

Refractory immune thrombocytopenia: Lessons from immune dysregulation disorders.

Frontiers in medicine
2022

Clinical and immunological analysis of a large kindred affected by autoimmune lymphoproliferative syndrome (ALPS) due to a novel TNFRSF6 mutation displaying age dependent disease activity.

Clinical immunology (Orlando, Fla.)
2022

Various phenotypes of LRBA gene with compound heterozygous variation: A case series report of pediatric cytopenia patients.

International journal of immunopathology and pharmacology
2023

Novel Germline TET2 Mutations in Two Unrelated Patients with Autoimmune Lymphoproliferative Syndrome-Like Phenotype and Hematologic Malignancy.

Journal of clinical immunology
2022

Abnormal B-Cell Maturation and Increased Transitional B Cells in CBL Syndrome.

Frontiers in pediatrics
2022

Case report: Effectiveness of sirolimus in a de novo FAS mutation leading to autoimmune lymphoproliferative syndrome-FAS and elevated DNT/Treg ratio.

Frontiers in pediatrics
2022

Diagnostic Challenges in Patients with Inborn Errors of Immunity with Different Manifestations of Immune Dysregulation.

Journal of clinical medicine
2022

Beyond Infections: New Warning Signs for Inborn Errors of Immunity in Children.

Frontiers in pediatrics
2022

Clinical exome sequencing of 1000 families with complex immune phenotypes: Toward comprehensive genomic evaluations.

The Journal of allergy and clinical immunology
2022

Super-Resolution Imaging of Fas/CD95 Reorganization Induced by Membrane-Bound Fas Ligand Reveals Nanoscale Clustering Upstream of FADD Recruitment.

Cells
2022

Utility of targeted next generation sequencing for inborn errors of immunity at a tertiary care centre in North India.

Scientific reports
2022

Sirolimus Restores Erythropoiesis and Controls Immune Dysregulation in a Child With Cartilage-Hair Hypoplasia: A Case Report.

Frontiers in immunology
2022

Underlying Inborn Errors of Immunity in Patients With Evans Syndrome and Multilineage Cytopenias: A Single-Centre Analysis.

Frontiers in immunology
2022

Stranded because of exhaustion while high-altitude mountaineering in the Swiss Alps: a retrospective nationwide study.

Scientific reports
2022

Differential Expression of Proteins in an Atypical Presentation of Autoimmune Lymphoproliferative Syndrome.

International journal of molecular sciences
2022

Deficiency of Human Adenosine Deaminase Type 2 - A Diagnostic Conundrum for the Hematologist.

Frontiers in immunology
2022

Lipopolysaccharide Responsive Beige-like Anchor Protein Deficiency in a Patient with Autoimmune Lymphoproliferative Syndrome-like Disease Phenotype: A Case Report and Literature Review.

Iranian journal of allergy, asthma, and immunology
2022

Increased mTORC2 pathway activation in lymph nodes of iMCD-TAFRO.

Journal of cellular and molecular medicine
2022

Case Report: Atypical Manifestations Associated With FOXP3 Mutations. The "Fil Rouge" of Treg Between IPEX Features and Other Clinical Entities?

Frontiers in immunology
2022

The contribution of rare copy number variants in FAS toward pathogenesis of autoimmune lymphoproliferative syndrome.

Blood advances
2022

A unique phenotype of longitudinal extensive transverse myelitis in autoimmune lymphoproliferative syndrome.

Journal of neuroimmunology
2022

Inborn errors of immunity and immunodeficiencies: Antibody-mediated pathology and autoimmunity as a consequence of impaired immune reactions.

European journal of immunology
2022

PAMI Syndrome: Two Cases of an Autoinflammatory Disease with an ALPS-Like Phenotype.

Journal of clinical immunology
2022

Genomics Driving Diagnosis and Treatment of Inborn Errors of Immunity With Cancer Predisposition.

The journal of allergy and clinical immunology. In practice
2022

Rheumatologic diseases in patients with inborn errors of immunity in the USIDNET registry.

Clinical rheumatology
2022

[Non-malignant, non-infectious lymphoproliferation: challenges in the diagnosis and treatment of autoimmune lymphoproliferative syndrome].

Orvosi hetilap
2022

Caspase-8 auto-cleavage regulates programmed cell death and collaborates with RIPK3/MLKL to prevent lymphopenia.

Cell death and differentiation
2022

ALPS, FAS, and beyond: from inborn errors of immunity to acquired immunodeficiencies.

Annals of hematology
2021

Autoimmune Cytopenias and Dysregulated Immunophenotype Act as Warning Signs of Inborn Errors of Immunity: Results From a Prospective Study.

Frontiers in immunology
2021

Case Report: Autoimmune Lymphoproliferative Syndrome vs. Chronic Active Epstein-Barr Virus Infection in Children: A Diagnostic Challenge.

Frontiers in pediatrics
2021

STAT3 gain-of-function mutation in an adult patient.

Medicina
2022

Impact of human CD95 mutations on cell death and autoimmunity: a model.

Trends in immunology
2021

Fevers, Sweats, Weight Loss, Oh My! When IgG4 Related Disease Comes Knocking. . .

Clinical medicine insights. Case reports
2021

Case Report: Deficiency of Adenosine Deaminase 2 Presenting With Overlapping Features of Autoimmune Lymphoproliferative Syndrome and Bone Marrow Failure.

Frontiers in immunology
2021

Case Report: FOXP3 Mutation in a Patient Presenting With ALPS.

Frontiers in immunology
2022

Large deletion in 6q containing the TNFAIP3 gene associated with autoimmune lymphoproliferative syndrome.

Clinical immunology (Orlando, Fla.)
2021

We refuse to die - T cells causing havoc.

Biomedical journal
2021

Presentation and diagnosis of autoimmune lymphoproliferative syndrome (ALPS).

Expert review of clinical immunology
2022

Paratrabecular bone marrow involvement in autoimmune lymphoproliferative syndrome: a potential diagnostic pitfall as a lymphoma mimic.

Histopathology
2022

Increased double-negative αβ+ T-cells reveal adult-onset autoimmune lymphoproliferative syndrome in a patient with IgG4-related disease.

Haematologica
2021

Type I interferon activation in RAS-associated autoimmune leukoproliferative disease (RALD).

Clinical immunology (Orlando, Fla.)
2021

Primary Immune Regulatory Disorders With an Autoimmune Lymphoproliferative Syndrome-Like Phenotype: Immunologic Evaluation, Early Diagnosis and Management.

Frontiers in immunology
2021

Scaling the tips of the ALPS.

Biomedical journal
2022

Autoimmune lymphoproliferative syndrome with Langerhans cell histiocytosis diagnosis.

Pediatric blood &amp; cancer
2021

Immune checkpoint deficiencies and autoimmune lymphoproliferative syndromes.

Biomedical journal
2021

Variants in CASP10, a diagnostic challenge: Single center experience and review of the literature.

Clinical immunology (Orlando, Fla.)
2021

Etiological causes and prognosis in children with neutropenia.

Northern clinics of Istanbul
2021

Sirolimus is effective in autoimmune lymphoproliferative syndrome-type III: A pedigree case report with homozygous variation PRKCD.

International journal of immunopathology and pharmacology
2021

The genetic landscape of the FAS pathway deficiencies.

Biomedical journal
2021

Genetic Characterization of Short Stature Patients With Overlapping Features of Growth Hormone Insensitivity Syndromes.

The Journal of clinical endocrinology and metabolism
2021

Pancytopenia and acute glomerulonephritis in an adolescent: Answers.

Pediatric nephrology (Berlin, Germany)
2021

Generalized Lymphadenopathy with Cytopenias.

The American journal of medicine
2021

Lymphadenopathy at the crossroad between immunodeficiency and autoinflammation: An intriguing challenge.

Clinical and experimental immunology
2021

Next Generation Sequencing for Detecting Somatic FAS Mutations in Patients With Autoimmune Lymphoproliferative Syndrome.

Frontiers in immunology
2021

Complete CD95/FAS deficiency due to complex homozygous germline TNFRSF6 mutations in an adult patient with mild autoimmune lymphoproliferative syndrome (ALPS).

Clinical immunology (Orlando, Fla.)
2021

Role of γ-Secretase Inhibitors for the Treatment of Diverse Disease Conditions through Inhibition of Notch Signaling Pathway.

Current drug targets
2021

Clinical, immunological, and genetic features in 780 patients with autoimmune lymphoproliferative syndrome (ALPS) and ALPS-like diseases: A systematic review.

Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology
2022

The challenge of early diagnosis of autoimmune lymphoproliferative syndrome in children with suspected autoinflammatory/autoimmune disorders.

Rheumatology (Oxford, England)
2021

Polyclonal hypergammaglobulinaemia: assessment, clinical interpretation, and management.

The Lancet. Haematology
2021

Immune cytopenias as a continuum in inborn errors of immunity: An in-depth clinical and immunological exploration.

Immunity, inflammation and disease
2021

Case Report: A Novel Pathogenic Missense Mutation in FAS: A Multi-Generational Case Series of Autoimmune Lymphoproliferative Syndrome.

Frontiers in pediatrics
2021

Successful treatment of acute myeloid leukemia and mast cell proliferation in a patient with autoimmune lymphoproliferative syndrome.

Pediatric blood &amp; cancer
2021

Underlying CTLA4 Deficiency in a Patient With Juvenile Idiopathic Arthritis and Autoimmune Lymphoproliferative Syndrome Features Successfully Treated With Abatacept-A Case Report.

Journal of pediatric hematology/oncology
2021

Refractory autoimmune cytopenias in pediatric Evans syndrome with underlying systemic immune dysregulation.

European journal of haematology
2020

Case Report: Signal Transducer and Activator of Transcription 3 Gain-of-Function and Spectrin Deficiency: A Life-Threatening Case of Severe Hemolytic Anemia.

Frontiers in immunology
2020

More than an 'atypical' phenotype: dual molecular diagnosis of autoimmune lymphoproliferative syndrome and Becker muscular dystrophy.

British journal of haematology
2021

Autoimmune Lymphoproliferative Syndrome in Children with Nonmalignant Organomegaly, Chronic Immune Cytopenia, and Newly Diagnosed Lymphoma.

Turkish journal of haematology : official journal of Turkish Society of Haematology
2021

Immunologic evaluation and genetic defects of apoptosis in patients with autoimmune lymphoproliferative syndrome (ALPS).

Critical reviews in clinical laboratory sciences
2020

Anaesthetic management of an emergency caesarean section in a complex immunologically compromised patient with pre-eclampsia and multifactorial thrombocytopaenia.

Anaesthesia reports
2021

A distinct CD38+CD45RA+ population of CD4+, CD8+, and double-negative T cells is controlled by FAS.

The Journal of experimental medicine
2020

[Lymphoproliferative disorders and inborn errors of immunity].

[Rinsho ketsueki] The Japanese journal of clinical hematology
2021

Persistent Interferon Production by Double Negative T Cells and Collapsing Focal Segmental Glomerulosclerosis.

Nephron
2022

Protein Kinase C-Delta Defect in Autoimmune Lymphoproliferative Syndrome-Like Disease: First Case from the National Iranian Registry and Review of the Literature.

Immunological investigations
2021

Clinical Spectrum of Ras-Associated Autoimmune Leukoproliferative Disorder (RALD).

Journal of clinical immunology
2020

Integration of innate immune signalling by caspase-8 cleavage of N4BP1.

Nature
2020

[; CLINICAL CASE OF STAT3 GOF IMMUNE DYSREGULATION DISEASE, ALPS].

Georgian medical news
2021

Unraveling subcutaneous panniculitis-like T-cell lymphoma: An association between subcutaneous panniculitis-like T-cell lymphoma, autoimmune lymphoproliferative syndrome, and familial hemophagocytic lymphohistiocytosis.

Journal of cutaneous pathology
2020

Defective FAS-Mediated Apoptosis and Immune Dysregulation in Gaucher Disease.

The journal of allergy and clinical immunology. In practice
2021

ITK deficiency presenting as autoimmune lymphoproliferative syndrome.

The Journal of allergy and clinical immunology
2020

Key diagnostic markers for autoimmune lymphoproliferative syndrome with molecular genetic diagnosis.

Blood
2020

Successful Artery Embolization in a Patient with Autoimmune Lymphoproliferative Syndrome Associated with Splenic Rupture.

Journal of clinical immunology
2020

Germline TET2 loss of function causes childhood immunodeficiency and lymphoma.

Blood
2020

Bartonella endocarditis mimics the clinical and immunologic findings of autoimmune lymphoproliferative syndrome.

Pediatric blood &amp; cancer
2020

Genetic heterogeneity of pediatric systemic lupus erythematosus with lymphoproliferation.

Medicine
2020

Caspase-8-Dependent Inflammatory Responses Are Controlled by Its Adaptor, FADD, and Necroptosis.

Immunity
2020

Novel Compound Heterozygote Variations in FADD Identified to Cause FAS-Associated Protein with Death Domain Deficiency.

Journal of clinical immunology
2020

Increased mTOR activation in idiopathic multicentric Castleman disease.

Blood
2020

Myeleterosis in an ALPS5 patient with primary immune dysregulation syndrome.

CNS neuroscience &amp; therapeutics
2021

Neonatal Autoimmune Lymphoproliferative Syndrome: A Case Report and A Brief Review.

Journal of pediatric hematology/oncology
2020

Autoimmune Lymphoproliferative Syndrome Presenting with Invasive Streptococcus pneumoniae Infection.

Journal of clinical immunology
2020

30 Years of Experience with Non-Hodgkin Lymphoma in Children and Adolescents: a retrospective cohort study.

Revista da Associacao Medica Brasileira (1992)
2019

[Autoimmune lymphoproliferative syndrome. Update and review].

Revista alergia Mexico (Tecamachalco, Puebla, Mexico : 1993)
2020

Flow Cytometry for the Diagnosis of Primary Immunodeficiency Diseases: A Single Center Experience.

Allergy, asthma &amp; immunology research
2019

Fatal Hypogammaglobulinemia 3 Years after Rituximab in a Patient with Immune Thrombocytopenia: An Underlying Genetic Predisposition?

Case reports in immunology
2019

Development of multiple gallstones in a child with lipopolysaccharide-responsive beige-like anchor protein mutation.

Central-European journal of immunology
2020

Causes of double-negative T-cell lymphocytosis in children and adults.

Journal of clinical pathology
2020

Defective glycosylation and multisystem abnormalities characterize the primary immunodeficiency XMEN disease.

The Journal of clinical investigation
2019

18F-FDG PET Imaging Features of Patients With Autoimmune Lymphoproliferative Syndrome.

Clinical nuclear medicine
2020

Lymphadenopathy, splenomegaly, intermittent neutropenia, and acute kidney injury: Answers.

Pediatric nephrology (Berlin, Germany)
2019

A Spectrum of Clinical Findings from ALPS to CVID: Several Novel LRBA Defects.

Journal of clinical immunology
2019

RAS-associated Autoimmune Leukoproliferative disease (RALD) manifested with early-onset SLE-like syndrome: a case series of RALD in Chinese children.

Pediatric rheumatology online journal
2019

Autoimmune Lymphoproliferative Syndrome with Cryptococcus Infection.

Journal of clinical immunology
Ver todos os 317 no EuropePMC

Associações

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Comunidades

Grupos ativos de quem convive com esta doença aqui no Raras

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Doenças relacionadas

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Referências e fontes

Bases de dados externas citadas neste artigo

Publicações científicas

Artigos indexados no PubMed ligados a esta doença no grafo RarasNet — título, periódico e PMID direto da fonte, sem intermediação de IA.

  1. Childhood isolated C3d-positive AIHA: favorable prognosis but rare relapse or associated immunodeficiency.
    Blood advances· 2026· PMID 41118608mais citado
  2. Lymphoproliferation in Inborn Errors of Immunity: Mechanisms, Manifestations and Clinical Management, with a Focus on ALPID.
    ImmunoTargets and therapy· 2026· PMID 41822009mais citado
  3. Monogenic Neonatal Diabetes: Clinical Presentations, Genetic Findings, and Response to Therapy in a Retrospective Case Series.
    Cureus· 2026· PMID 41769619mais citado
  4. Long-Term Outcomes of Successful Treatment with Ruxolitinib in a Pediatric Patient with Autoimmune Lymphoproliferative Syndrome and a Signal Transducer and Activator of Transcription 3 Gain-of-Function Mutation.
    Klinische Padiatrie· 2026· PMID 41760118mais citado
  5. CASP8 and CASP3 mRNA Expression in Autoimmune Lymphoproliferative Syndrome (ALPS) and Chronic Immune Thrombocytopenia (ITP).
    Genes· 2026· PMID 41751590mais citado
  6. A curated list of immune system associated genes related to cancer.
    BMC Genom Data· 2026· PMID 41851628recente

Bases de dados e fontes oficiais

Identificadores e referências canônicas usadas para montar este verbete.

  1. ORPHA:3261(Orphanet)
  2. MONDO:0017979(MONDO)
  3. GARD:8686(GARD (NIH))
  4. Variantes catalogadas(ClinVar)
  5. Busca completa no PubMed(PubMed)
  6. Q1151300(Wikidata)

Dados compilados pelo RarasNet a partir de fontes abertas (Orphanet, OMIM, MONDO, PubMed/EuropePMC, ClinicalTrials.gov, DATASUS, PCDT/MS). Este conteúdo é informativo e não substitui avaliação médica.

Conteúdo mantido por Agente Raras · Médicos e pesquisadores podem colaborar

Síndrome linfoproliferativo autoimune
Compêndio · Raras BR

Síndrome linfoproliferativo autoimune

ORPHA:3261 · MONDO:0017979
Prevalência
Unknown
Casos
500 casos conhecidos
Herança
Autosomal dominant, Autosomal recessive
CID-10
D47.9 · Neoplasia de comportamento incerto ou desconhecido dos tecidos linfático, hematopoético e tecidos correlatos, não especificada
CID-11
Ensaios
4 ativos
Início
All ages
Prevalência
0.0 (Worldwide)
MedGen
UMLS
C1328840
Testes
146 disponíveis
EuropePMC
Wikidata
Papers 10a
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