Autoantibodies Against Proteins Previously Associated With Autoimmunity in Adult and Pediatric Patients With COVID-19 and Children With MIS-C

Abstract

The antibody profile against autoantigens previously associated with autoimmune diseases and other human proteins in patients with COVID-19 or multisystem inflammatory syndrome in children (MIS-C) remains poorly defined. Here we show that 30% of adults with COVID-19 had autoantibodies against the lung antigen KCNRG, and 34% had antibodies to the SLE-associated Smith-D3 protein. Children with COVID-19 rarely had autoantibodies; one of 59 children had GAD65 autoantibodies associated with acute onset of insulin-dependent diabetes. While autoantibodies associated with SLE/Sjögren’s syndrome (Ro52, Ro60, and La) and/or autoimmune gastritis (gastric ATPase) were detected in 74% (40/54) of MIS-C patients, further analysis of these patients and of children with Kawasaki disease (KD), showed that the administration of intravenous immunoglobulin (IVIG) was largely responsible for detection of these autoantibodies in both groups of patients. Monitoring in vivo decay of the autoantibodies in MIS-C children showed that the IVIG-derived Ro52, Ro60, and La autoantibodies declined to undetectable levels by 45-60 days, but gastric ATPase autoantibodies declined more slowly requiring >100 days until undetectable. Further testing of IgG and/or IgA antibodies against a subset of potential targets identified by published autoantigen array studies of MIS-C failed to detect autoantibodies against most (16/18) of these proteins in patients with MIS-C who had not received IVIG. However, Troponin C2 and KLHL12 autoantibodies were detected in 2 of 20 and 1 of 20 patients with MIS-C, respectively. Overall, these results suggest that IVIG therapy may be a confounding factor in autoantibody measurements in MIS-C and that antibodies against antigens associated with autoimmune diseases or other human proteins are uncommon in MIS-C.

SARS-CoV-2 infection and recovery in children: Distinct T cell responses in MIS-C compared to COVID-19

“…The successful treatment of MIS-C with intravenous immunoglobulin (IVIG) and steroids further implicates systemic immune dysregulation in disease pathogenesis ( Belhadjer et al, 2020 ; Crosby et al, 2021 ). While circulating autoantibodies reactive to endothelial cell components may account for the cardiovascular dysfunction in acute MIS-C ( Burbelo et al, 2022 ; Porritt et al, 2021a ; Ramaswamy et al, 2021 ), the underlying mechanisms for mucosal tissue damage remain unclear. It is also not known whether the systemic inflammation observed in MIS-C is induced by SARS-CoV-2 infection or secondary effects of immune activation and/or tissue damage.…”

Evidence of a Sjögren’s disease-like phenotype following COVID-19

“…showed that autoantibodies are present in approximately 15% of healthy controls and 50% of COVID-19 patients against commonly recognized antigens in an array of autoimmune disorders, including SSA/Ro52 [38]. However, Burbelo, et al, 2022 demonstrated that a considerable fraction of the autoantibody positivity in severe COVID-19 subjects may be related to receipt of intravenous immunoglobulins (IVIG) [39]. Thus, these results suggest the need for longitudinally sampled and controlled serosurveillence need to be performed.…”

COVID-19 and autoimmune diseases: is there a connection?

“…Besides, some studies reported that children with MIS-C have a concomitant expansion of antibodies against other common respiratory viruses, including other coronaviruses, influenza, respiratory syncytial, and Epstein-Barr viruses [16]. Notably, children with MIS-C also show high levels of circulating autoantibodies, which were also found in samples taken prior to intravenous immunoglobulins (IVIG) administration [50,52,53].…”