Favorable antibody responses to human coronaviruses in children and adolescents with autoimmune rheumatic diseases

Differences in humoral immunity to coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), between children and adults remain unexplained, and the effect of underlying immune dysfunction or suppression is unknown. Here, we sought to examine the antibody immune competen...

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Published in:Med (New York, N.Y. : Online) N.Y. : Online), 2021-09, Vol.2 (9), p.1093-1109.e6
Main Authors: Deakin, Claire T., Cornish, Georgina H., Ng, Kevin W., Faulkner, Nikhil, Bolland, William, Hope, Joshua, Rosa, Annachiara, Harvey, Ruth, Hussain, Saira, Earl, Christopher, Jebson, Bethany R., Wilkinson, Meredyth G.L.l., Marshall, Lucy R., O’Brien, Kathryn, Rosser, Elizabeth C., Radziszewska, Anna, Peckham, Hannah, Patel, Harsita, Heaney, Judith, Rickman, Hannah, Paraskevopoulou, Stavroula, Houlihan, Catherine F., Spyer, Moira J., Gamblin, Steve J., McCauley, John, Nastouli, Eleni, Levin, Michael, Cherepanov, Peter, Ciurtin, Coziana, Wedderburn, Lucy R., Kassiotis, George
Format: Article
Language:English
Subjects:
Adolescent
Adult
Antibodies, Viral
Antibody Formation
antibody response
Autoimmune Diseases
Child
Clinical and Translational
Coronavirus OC43, Human
COVID-19 - complications
Humans
Immunoglobulin G
immunosuppression
nucleoprotein
Nucleoproteins
Rheumatic Diseases
SARS-CoV-2
seasonal coronavirus
Spike Glycoprotein, Coronavirus
spike protein
Systemic Inflammatory Response Syndrome
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Summary:Differences in humoral immunity to coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), between children and adults remain unexplained, and the effect of underlying immune dysfunction or suppression is unknown. Here, we sought to examine the antibody immune competence of children and adolescents with prevalent inflammatory rheumatic diseases, juvenile idiopathic arthritis (JIA), juvenile dermatomyositis (JDM), and juvenile systemic lupus erythematosus (JSLE) against the seasonal human coronavirus (HCoV)-OC43 that frequently infects this age group. Sera were collected from JIA (n = 118), JDM (n = 49), and JSLE (n = 30) patients and from healthy control (n = 54) children and adolescents prior to the coronavirus disease 19 (COVID-19) pandemic. We used sensitive flow-cytometry-based assays to determine titers of antibodies that reacted with the spike and nucleoprotein of HCoV-OC43 and cross-reacted with the spike and nucleoprotein of SARS-CoV-2, and we compared them with respective titers in sera from patients with multisystem inflammatory syndrome in children and adolescents (MIS-C). Despite immune dysfunction and immunosuppressive treatment, JIA, JDM, and JSLE patients maintained comparable or stronger humoral responses than healthier peers, which was dominated by immunoglobulin G (IgG) antibodies to HCoV-OC43 spike, and harbored IgG antibodies that cross-reacted with SARS-CoV-2 spike. In contrast, responses to HCoV-OC43 and SARS-CoV-2 nucleoproteins exhibited delayed age-dependent class-switching and were not elevated in JIA, JDM, and JSLE patients, which argues against increased exposure. Consequently, autoimmune rheumatic diseases and their treatment were associated with a favorable ratio of spike to nucleoprotein antibodies. This work was supported by a Centre of Excellence Centre for Adolescent Rheumatology Versus Arthritis grant, 21593, UKRI funding reference MR/R013926/1, the Great Ormond Street Children’s Charity, Cure JM Foundation, Myositis UK, Lupus UK, and the NIHR Biomedical Research Centres at GOSH and UCLH. This work was supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK, the UK Medical Research Council, and the Wellcome Trust. [Display omitted] IgG dominates the antibody responses to HCoV-OC43 spike in children and adolescentsResponse to the HCoV-OC43 nucleoprotein exhibits delayed age-dependent class-switchingHigher response to HCoV-OC43 spike but not nucleoprot
ISSN:2666-6340
2666-6359
2666-6340
DOI:10.1016/j.medj.2021.08.001