We present a unique case involving a patient who was diagnosed with X-linked properdin deficiency after 2 episodes of disseminated gonococcal infections 1 year apart. Although this deficiency is well-documented for its association with meningococcemia, its correlation with disseminated gonococcal infections (DGI) has not been previously reported. Recurrent DGI cases reported in the literature with identified cause are mostly associated with acquired or congenital complement pathway deficiencies. However, properdin deficiency is rarely screened for during a first episode. Our case not only highlights the clinical presentation that should raise suspicion of DGI but also underscores the importance of investigating the alternative complement pathway in such cases. At a time when gonococcal resistance is increasing, it is essential to consider existing strategies for preventing these infections, including vaccinations.

Invasive meningococcal diseases (IMD) caused by Neisseria meningitidis are generally rare. They affect mostly selected age categories and risk groups of patients (in terms of age, comorbidities, or applied therapy), and the immune system and its defects may play an important modifying role. Meningococcal infections could be the first and only clinical sign of unrecognised immunodeficiency. IMD are a typical clinical presentation of inborn errors of immunity with low concentrations or dysfunction of the terminal components of complement cascade. Meningitis is present in approximately 40% of the patients with terminal complement components deficiencies and in 6% of the patients with properdin deficiency. Despite evident advances in the understanding of the pathogenesis of meningococcal infections and the mechanisms of immune defence against this pathogen, patients with defects in the alternative or terminal complement pathway are highly predisposed to invasive and recurrent meningococcal infections, usually with a mild course. Therefore, it is recommended that each patient with IMD, especially recurrent, should undergo an immunological examination to rule out complement deficiencies.

A 13-year-old boy was admitted with severe meningococcal meningitis. Immunologic workup revealed a properdin deficiency, and genetic sequencing of CFP identified a novel, private and predicted pathogenic variant in exon 8. The patient received broad immunizations and penicillin prophylaxis. Children with invasive meningococcal disease should be tested for complement deficiency.

Phagocytosis plays vital roles in injury and repair, while its regulation by properdin and innate repair receptor, a heterodimer receptor of erythropoietin receptor (EPOR)/β common receptor (βcR), in renal ischaemia-reperfusion (IR) remains unclear. Properdin, a pattern recognition molecule, facilitates phagocytosis by opsonizing damaged cells. Our previous study showed that the phagocytic function of tubular epithelial cells isolated from properdin knockout (PKO) mouse kidneys was compromised, with upregulated EPOR in IR kidneys that was further raised by PKO at repair phase. Here, helix B surface peptide (HBSP), derived from EPO only recognizing EPOR/βcR, ameliorated IR-induced functional and structural damage in both PKO and wild-type (WT) mice. In particular, HBSP treatment led to less cell apoptosis and F4/80+ macrophage infiltration in the interstitium of PKO IR kidneys compared to the WT control. In addition, the expression of EPOR/βcR was increased by IR in WT kidneys, and furthered increased in IR PKO kidneys, but greatly reduced by HBSP in the IR kidneys of PKO mice. HBSP also increased PCNA expression in IR kidneys of both genotypes. Moreover, iridium-labelled HBSP (HBSP-Ir) was localized mainly in the tubular epithelia after 17-h renal IR in WT mice. HBSP-Ir also anchored to mouse kidney epithelial (TCMK-1) cells treated by H2O2. Both EPOR and EPOR/βcR were significantly increased by H2O2 treatment, while further increased EPOR was showed in cells transfected with small interfering RNA (siRNA) targeting properdin, but a lower level of EPOR was seen in EPOR siRNA and HBSP-treated cells. The number of early apoptotic cells was increased by EPOR siRNA in H2O2-treated TCMK-1, but markedly reversed by HBSP. The phagocytic function of TCMK-1 cells assessed by uptake fluorescence-labelled E.coli was enhanced by HBSP dose-dependently. Our data demonstrate for the first time that HBSP improves the phagocytic function of tubular epithelial cells and kidney repair post IR injury, via upregulated EPOR/βcR triggered by both IR and properdin deficiency.