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.
Highlights
Coronavirus disease 2019 (COVID-19) caused by the SARSCoV-2 virus, is associated with a high rate of respiratory-related mortality [1]
Testing of two commonly found autoantibody targets, IL-1a and Jo-1, that have been observed in both healthy persons and patients with myositis, respectively, revealed low level autoantibodies in intravenous immunoglobulin (IVIG) just above the cut-off value derived from control children. Together these results suggest that the Ro52, Ro60, La, and gastric ATPase autoantibodies observed in MIS-C and Kawasaki disease (KD) patients were due to prior infusion of high-dose IVIG and that other autoantibodies found in IVIG preparations may contribute to anomalous autoantibody seropositivity, Longitudinal Analysis of SARS-CoV-2 Autoantibodies in Children With MIS-C and KD
Analysis of adult patients with COVID-19 showed a moderate frequency of autoantibody positivity against several autoantigens including the lung protein KCNRG (30%) and the systemic lupus erythematosus (SLE) antigen Sm-D3 (34%)
Summary
Coronavirus disease 2019 (COVID-19) caused by the SARSCoV-2 virus, is associated with a high rate of respiratory-related mortality [1]. The variability in clinical symptoms with COVID-19 likely involves sites of virus and viral antigen localization, vascular complications associated with the infection, the level of inflammation, and host factors including genetics, age, gender, and coexistence of other comorbid conditions [3]. One major immune pathway involved in limiting SARS-CoV-2 infection is the type I interferon (IFN) pathway. Evidence for its role is based on genetic studies showing that individuals with inborn errors of type I IFN are at higher risk of severe COVID-19 [6]. Neutralizing autoantibodies to IFN-a and/or -w occur in approximately 10% of patients with severe COVID-19 pneumonia, especially men, and blunt effective clearance of the virus, likely contributing to death [7]
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