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
Affiliations
- Peter D. Burbelo
- National Institute of Dental and Craniofacial Research, NIH, Bethesda, MD, United States
- Riccardo Castagnoli
- Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, United States
- Riccardo Castagnoli
- Department of Pediatrics, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy
- Chisato Shimizu
- Department of Pediatrics, Rady Children’s Hospital, University of California San Diego, San Diego, CA, United States
- Ottavia M. Delmonte
- Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, United States
- Kerry Dobbs
- Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, United States
- Valentina Discepolo
- Department of Translational Medical Science, Section of Pediatrics, University of Naples Federico II, Naples, Italy
- Andrea Lo Vecchio
- Department of Translational Medical Science, Section of Pediatrics, University of Naples Federico II, Naples, Italy
- Alfredo Guarino
- Department of Translational Medical Science, Section of Pediatrics, University of Naples Federico II, Naples, Italy
- Francesco Licciardi
- Division of Pediatric Immunology and Rheumatology, Department of Public Health and Pediatric Sciences, “Regina Margherita” Children’s Hospital, University of Turin, Turin, Italy
- Ugo Ramenghi
- Division of Pediatric Immunology and Rheumatology, Department of Public Health and Pediatric Sciences, “Regina Margherita” Children’s Hospital, University of Turin, Turin, Italy
- Emma Rey-Jurado
- Instituto de Ciencias e Innovación en Medicina (ICIM), Clínica Alemana Universidad del Desarrollo, Santiago, Chile
- Cecilia Vial
- Instituto de Ciencias e Innovación en Medicina (ICIM), Clínica Alemana Universidad del Desarrollo, Santiago, Chile
- Gian Luigi Marseglia
- Department of Pediatrics, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy
- Amelia Licari
- Department of Pediatrics, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy
- Daniela Montagna
- Department of Pediatrics, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy
- Camillo Rossi
- Direzione Sanitaria, ASST Spedali Civili, Brescia, Italy
- Gina A. Montealegre Sanchez
- Intramural Clinical Management and Operations Branch (ICMOB), Division of Clinical Research NIAID, NIH, Bethesda, MD, United States
- Karyl Barron
- 0Division of Intramural Research, National Institute of Allergy and Infectious Disease, NIH, Bethesda, MD, United States
- Blake M. Warner
- National Institute of Dental and Craniofacial Research, NIH, Bethesda, MD, United States
- John A. Chiorini
- National Institute of Dental and Craniofacial Research, NIH, Bethesda, MD, United States
- Yazmin Espinosa
- 1Hospital Roberto del Río, Santiago, Chile
- Loreani Noguera
- Instituto de Ciencias e Innovación en Medicina (ICIM), Clínica Alemana Universidad del Desarrollo, Santiago, Chile
- Lesia Dropulic
- 2Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, United States
- Meng Truong
- Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, United States
- Dana Gerstbacher
- 3Pediatric Rheumatology, Stanford Children’s Hospital, Stanford, CA, United States
- Sayonara Mató
- 4Pediatric Infectious Diseases, Randall Children’s Hospital at Legacy Emanuel, Portland, OR, United States
- John Kanegaye
- Department of Pediatrics, Rady Children’s Hospital, University of California San Diego, San Diego, CA, United States
- Adriana H. Tremoulet
- Department of Pediatrics, Rady Children’s Hospital, University of California San Diego, San Diego, CA, United States
- Pediatric Emergency Medicine Kawasaki Group
- Eli M. Eisenstein
- 5Department of Pediatrics, Hadassah Medical Center, Faculty of Medicine, Hebrew University, Jerusalem, Israel
- Helen C. Su
- Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, United States
- Luisa Imberti
- 6CREA Laboratory, Diagnostic Department, ASST Spedali Civili di Brescia, Brescia, Italy
- Maria Cecilia Poli
- Instituto de Ciencias e Innovación en Medicina (ICIM), Clínica Alemana Universidad del Desarrollo, Santiago, Chile
- Maria Cecilia Poli
- 1Hospital Roberto del Río, Santiago, Chile
- Jane C. Burns
- Department of Pediatrics, Rady Children’s Hospital, University of California San Diego, San Diego, CA, United States
- Luigi D. Notarangelo
- Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, United States
- Jeffrey I. Cohen
- 2Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, United States
- 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
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
