Autoantibodies Against Proteins Previously Associated With Autoimmunity in Adult and Pediatric Patients With COVID-19 and Children With MIS-C
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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.
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SciScore for 10.1101/2021.11.03.21265769: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: Città della Salute e della Scienza di Torino, Protocol: 00282/2020); Naples, Italy (Ethics Committee of the University of Naples Federico II, Protocol: 158/20); Chile (Comité Ético Científico Facultad de Medicina Clínica Alemana Universidad del Desarrollo, Santiago, Chile, Protocol: 2020-41); and Israel (Hadassah Medical Organization Institutional Review Board (IRB) for studies involving human subjects, Protocol: HMO-235-20).
Consent: Additional MIS-C patients were enrolled from other sources including Stanford, California and Portland, Oregon, after written informed consent to NIH IRB-approved research protocols (NIH Protocols l1-1-0109, 18-I-0041 and 18-I-0128).Sex as a biological … SciScore for 10.1101/2021.11.03.21265769: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: Città della Salute e della Scienza di Torino, Protocol: 00282/2020); Naples, Italy (Ethics Committee of the University of Naples Federico II, Protocol: 158/20); Chile (Comité Ético Científico Facultad de Medicina Clínica Alemana Universidad del Desarrollo, Santiago, Chile, Protocol: 2020-41); and Israel (Hadassah Medical Organization Institutional Review Board (IRB) for studies involving human subjects, Protocol: HMO-235-20).
Consent: Additional MIS-C patients were enrolled from other sources including Stanford, California and Portland, Oregon, after written informed consent to NIH IRB-approved research protocols (NIH Protocols l1-1-0109, 18-I-0041 and 18-I-0128).Sex as a biological variable Serum samples from adults with COVID-19 (n=80) in Brescia, Italy were obtained from a higher number of male than female (48:32) patients with a median age of 55 years (interquartile range (IQR): 45-66), and a median time between blood draw and onset of symptoms of 25 days (IQR: 13-52). Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Antibodies Sentences Resources In addition to testing the IVIG preparation for autoantibodies against Ro52, Ro60, La and the gastric ATPase, several additional autoantigens were tested including Jo-1 [30] and IL-1 alpha [35]. Ro52suggested: NoneRo60suggested: NoneIL-1suggested: NoneSoftware and Algorithms Sentences Resources A selected panel of autoantigens representing both ubiquitous and tissue-specific antigens were first tested in adults and included: Ro52, Ro60, La, RNP-A, Sm-D3, Jo-1, gastric ATPase (ATPB4 subunit), LGI1, U170K, CENP-A, RNAP-K, BPIFB1, defensin 5A, KCNRG, glutamic acid decarboxylase (GAD65), gastric inhibitory factor (GIF), and M-type phospholipase A2 receptor (PLA2R). GIFsuggested: NoneStatistical analysis: GraphPad Prism software (San Diego, CA) was used for analyzing the antibody levels in this study. GraphPad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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