Antiphospholipid antibody (aPL) syndrome (APS) classification requires a thrombotic event and detection of lupus anticoagulant (LAC), anticardiolipin antibodies (aCL), or anti-β2-glycoprotein I (anti-β2GPI) antibodies on two occasions ≥12 weeks apart. Here, we investigated the utility of anti-phosphatidylserine/prothrombin complex (anti-PS/PT) aPL in patients with APS with and without concurrent systemic lupus erythematosus (SLE) with the aim to improve disease disease classification and clinical care. A total of 1,286 patients were tested for presence of IgA, IgG, and IgM anti-phosphatidylserine/prothrombin complex (anti-PS/PT) antibodies along with IgA, IgM, and IgG anti-β2GPI and aCL and LAC assays, including hexagonal phase phospholipid neutralization assay (HPPNA), dilute Russell's viper venom time (dRVVT), and platelet neutralization procedures (PNP). Statistical analyses were performed with the chi-square test using Bonferroni correction for multiple comparisons. A total of 324 patients with SLE, 88 patients with APS, and 54 patients with concurrent SLE and APS had simultaneous testing for IgA, IgG, and IgM anti-PS/PT, aCL, and anti-β2GPI antibodies and HPPNA, dRVVT, and PNP LAC assays. IgM anti-PS/PT antibody was sensitive for discriminating patients with SLE (P = 0.0024), APS (P < 0.0001), and SLE and APS from those without either diagnosis (P < 0.0001). IgG anti-PS/PT antibody discriminated patients with APS (P < 0.0001) and SLE and APS from those without either diagnosis (P < 0.0001). Among 46 patients with SLE lacking aCL, anti-β2GPI aPL, LAC, or any clinical manifestation of APS, 35 patients only had IgM anti-PS/PT antibodies, whereas 11 different patients only had IgG anti-PS/PT antibodies. These results demonstrate a significant utility of IgM and IgG anti-PS/PT antibody testing for more precise classification of SLE and more sensitive diagnosis and timely treatment of patients with relevant thrombotic clinical manifestations.

N-chlorotaurine (NCT) a long-lived oxidant generated by leukocytes, can be synthesized chemically and applied topically as an anti-infective to different body sites, including the lung via inhalation. Here, we demonstrate the activity of NCT against viruses causing acute respiratory tract infections, namely severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza viruses, and respiratory syncytial virus (RSV). Virucidal activity of NCT was tested in plaque assays, confirmed by RT-qPCR assays. Attack on virus proteins was investigated by mass spectrometry. NCT revealed broad virucidal activity against all viruses tested at 37°C and pH 7. A significant reduction in infectious particles of SARS-CoV-2 isolates from early 2020 by 1 log10 was detected after 15 min of incubation in 1% NCT. Proteinaceous material simulating body fluids enhanced this activity by transchlorination mechanisms (1 -2 log10 reduction within 1-10 min). Tested SARS-CoV-2 variants B.1.1.7 (Alpha) und B.1.351 (Beta) showed a similar susceptibility. Influenza virus infectious particles were reduced by 3 log10 (H3N2) to 5 log10 (H1N1pdm), RSV by 4 log10 within a few min. Mass spectrometry of NCT-treated SARS-CoV-2 spike protein and 3C-like protease, influenza virus haemagglutinin and neuraminidase, and RSV fusion glycoprotein disclosed multiple sites of chlorination and oxidation as the molecular mechanism of action. Application of 1.0% NCT as a prophylactic and therapeutic strategy against acute viral respiratory tract infections deserves comprehensive clinical investigation.

We describe a 64-year-old Caucasian female with a history of Raynaud's disease, hand arthritis, photosensitivity, Sjogren's syndrome and leukocytoclastic vasculitis who presented with progressively worsening fingertip necrosis that began three days after receiving a first dose of Pfizer-BioNTech COVID-19 RNA vaccine. Our workup revealed cryoglobulinemia, hypocomplementemia, elevated antinuclear antibodies (ANA) and IgM antiphospholipid autoantibodies (aPL) directed against phosphatidylserine (aPL-PS), suggesting a diagnosis of systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). The patient failed to develop anti-spike IgG antibodies up to two months following vaccination. Disease progression was halted by plasmapheresis, anticoagulation, and immune suppression. We conclude that the vaccine RNA moiety may induce SLE manifesting in APS, cryoglobulinemia, hypocomplementemia, and digital necrosis.

The rapid spread of the virus in Latin America and the association of the infection with microcephaly in newborns or Guillain-Barré Syndrome in adults prompted the WHO to declare the Zika virus (ZIKV) epidemic to be an international public health emergency in 2016. As the virus was first discovered in monkeys and is spread not only by mosquitos but also from human to human, we investigated the stability to the human complement of ZIKV derived from mosquito (ZIKVInsect), monkey (ZIKVVero), or human cells (ZIKVA549 and ZIKVFibro), respectively. At a low serum concentration (10%), which refers to complement concentrations found on mucosal surfaces, the virus was relatively stable at 37 °C. At higher complement levels (up to 50% serum concentration), ZIKV titers differed significantly depending on the cell line used for the propagation of the virus. While the viral titer of ZIKVInsect decreased about two orders in magnitude, when incubated with human serum, the virus derived from human cells was more resistant to complement-mediated lysis (CML). By virus-capture assay and Western blots, the complement regulator protein CD55 was identified to be incorporated into the viral envelope. Blocking of CD55 by neutralizing Abs significantly increased the sensitivity to human complement. Taken together, these data indicate that the incorporation of CD55 from human cells contributes to the stability of ZIKV against complement-mediated virolysis.

Here, we present a 22-year-old female patient with adult-onset Still's disease (AOSD) who was newly diagnosed in the setting of secondary macrophage activation syndrome (MAS), a rare, life-threatening inflammatory disease with 50% mortality due to multi-organ failure. She met the diagnostic criteria of AOSD and MAS, while genetic testing excluded primary causes of MAS. She had high fevers, anemia, thrombocytopenia, splenomegaly, hematophagocytosis, and elevated serum ferritin (37,950 ng/mL) and CD25 levels (11,870 pg/mL), which remained unresponsive to corticosteroids and anakinra. Her serum interferon gamma (IFN-γ) levels were elevated (7 pg/mL). She was markedly responsive to IFN-γ blockade with emapalumab that eliminated her fevers and all MAS-associated laboratory abnormalities. This report provides initial evidence for therapeutic efficacy for IFN-γ blockade in AOSD and secondary MAS.