ObjectiveThe worldwide COVID-19 vaccination campaign triggered several autoimmune diseases. We hereby aimed to describe IgA vasculitis (IgAV) following COVID- 19 vaccination.MethodsWe conducted a French national multi-centre, retrospective study of new onset adult IgAV diagnosis following COVID-19 vaccination.ResultsTwelve patients with a new onset IgAV were included. Five were women (41.6%), and the median age was 52,5 years IQR [30.75-60.5]. Ten received an mRNA vaccine. Two patients received a viral vector vaccine. The median time from vaccination to onset of symptoms was 11.5 days with an IQR of [4.25-21.25]. The vasculitis occurred after the first vaccine dose in most patients (n=8). All patients had skin involvement, with skin necrosis in four patients. Seven patients had joint involvement and 2 had arthritis. Four had non-severe gastrointestinal involvement. Two had non-severe renal involvement. Median C-reactive protein was 26 mg/l [10-66.75], median creatininaemia was 72 μmol/l [65-81], one patient had eGFR < 60 ml/min at management. All patients received a treatment, including glucocorticosteroids in 9 patients (75%). Five patients received a vaccine dose after developing IgAV, one of them experienced a minor cutaneous relapse.ConclusionBaseline presentation of IgAV following COVID-19 vaccination was mild to moderate and outcomes were favourable. Thus, a complete COVID-19 vaccination regimen should be completed in this population. Of note, a fortuitous link cannot be ruled out requiring a worldwide pharmacovigilance search now to confirm these findings.

ObjectiveIgA vasculitis (IgAV) can occur after vaccination. We aimed to assess a potential safety signal on the association between COVID-19 vaccines and IgAV.MethodsCases of IgAV involving COVID-19 vaccines were retrieved in Vigibase. Disproportionate reporting was assessed using the Bayesian information component with all other drugs and vaccines as control groups.ResultsThree hundred and thirty de novo IgAV from 24 countries were included, mostly in United States (193/330, 58%). Fifty per cent were female (163/328), median age was 32 years [interquartile range (IQR), 15-59] of which 33% (84/254) were young (1-17 years). Median time to onset of IgAV was 7 days (IQR, 2-16; n=256) and 85% of patients (280/330) were vaccinated with mRNA vaccines. Seriousness was reported in 188 cases (58%). Ninety-five recovered (65%) and 2 died (2%). A positive rechallenge was reported for 3 of 4 patients (75%).A total of 996 cases of IgAV were identified with other vaccines. There was a small significant increase in IgAV reporting with COVID-19 vaccines compared with all other drugs (IC 0.22, credibility interval (CrI) from 0.04 to 0.35). No disproportionality signal was found between COVID-19 and other vaccines (IC -1.42, CrI from -1.60 to -1.28]). There was no significant difference between mRNA vaccines and viral vector COVID-19 vaccines. Men and children had a significant overreporting of IgAV compared with women and adults, respectively.ConclusionThis study, provides reassuring results regarding the safety of COVID-19 vaccines in the occurrence of IgAV compared to other vaccines.

Understanding the biological mechanisms underlying the pH-dependent nature of FcRn binding, as well as the various factors influencing the affinity to FcRn, was concurrent with the arrival of the first recombinant IgG monoclonal antibodies (mAbs) and IgG Fc-fusion proteins in clinical practice. IgG Fc–FcRn became a central subject of interest for the development of these drugs for the comfort of patients and good clinical responses. In this review, we describe (i) mAb mutations close to and outside the FcRn binding site, increasing the affinity for FcRn at acidic pH and leading to enhanced mAb half-life and biodistribution, and (ii) mAb mutations increasing the affinity for FcRn at acidic and neutral pH, blocking FcRn binding and resulting, in vivo, in endogenous IgG degradation. Mutations modifying FcRn binding are discussed in association with pH-dependent modulation of antigen binding and (iii) anti-FcRn mAbs, two of the latest innovations in anti-FcRn mAbs leading to endogenous IgG depletion. We discuss the pharmacological effects, the biological consequences, and advantages of targeting IgG–FcRn interactions and their application in human therapeutics.

The neonatal Fc receptor (FcRn) is a ubiquitously expressed protein historically involved in IgG and albumin recycling. Recent data suggest an involvement in the pathophysiology of antibody-mediated autoimmune diseases. Among them, systemic lupus erythematosus (SLE) implies clinical and biological abnormalities of innate and adaptive circulating immune cells, potentially involving newly described functions of FcRn. In this study, FcRn expression was assessed by flow cytometry in peripheral blood leukocytes of 41 SLE patients with either active or inactive disease and 32 healthy donors. FcRn expression in B cells, natural killer cells, and T cells of SLE patients was statistically lower as compared to healthy donors. Conversely, FcRn level was statistically higher in non-classical monocyte subpopulations (CD14+CD16+ monocytes) of SLE patients versus healthy donors providing an interesting perspective to further explore its role in SLE pathophysiology.