Frontiers in Immunology (Mar 2022)

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

  • Peter D. Burbelo,
  • Riccardo Castagnoli,
  • Riccardo Castagnoli,
  • Chisato Shimizu,
  • Ottavia M. Delmonte,
  • Kerry Dobbs,
  • Valentina Discepolo,
  • Andrea Lo Vecchio,
  • Alfredo Guarino,
  • Francesco Licciardi,
  • Ugo Ramenghi,
  • Emma Rey-Jurado,
  • Cecilia Vial,
  • Gian Luigi Marseglia,
  • Amelia Licari,
  • Daniela Montagna,
  • Camillo Rossi,
  • Gina A. Montealegre Sanchez,
  • Karyl Barron,
  • Blake M. Warner,
  • John A. Chiorini,
  • Yazmin Espinosa,
  • Loreani Noguera,
  • Lesia Dropulic,
  • Meng Truong,
  • Dana Gerstbacher,
  • Sayonara Mató,
  • John Kanegaye,
  • Adriana H. Tremoulet,
  • Pediatric Emergency Medicine Kawasaki Group,
  • Eli M. Eisenstein,
  • Helen C. Su,
  • Luisa Imberti,
  • Maria Cecilia Poli,
  • Maria Cecilia Poli,
  • Jane C. Burns,
  • Luigi D. Notarangelo,
  • Jeffrey I. Cohen,
  • Naomi Abe,
  • Amy Bryl,
  • J. Joelle Donofrio-Odmann,
  • Atim Ekpenyong, ,
  • Michael Gardiner, ,
  • David J. Gutglass,
  • Margaret B. Nguyen,
  • Stacey Ulrich

DOI
https://doi.org/10.3389/fimmu.2022.841126
Journal volume & issue
Vol. 13

Abstract

Read online

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.

Keywords