MIS-C in children: A distinct autoimmune response to COVID-19 unveiled MISC Research SARSCoV2 CrossReactivity SNX8Protein InflammatorySyndrome PostViral ImmuneResponse medrxivpreprint
By Dr. Chinta SidharthanJun 8 2023Reviewed by Benedette Cuffari, M.Sc. In a recent study posted to the medRxiv* preprint server, researchers examine a large dataset of patients with multisystem inflammatory syndrome in children to determine whether their autoantibodies target a different set of host proteins as compared to healthier controls.
Background Severe acute respiratory syndrome coronavirus 2 infection can lead to long-term dysregulation of the immune system and a broad spectrum of secondary infections and diseases, including post-acute sequelae of coronavirus disease 2019 in adults. In children, while the outcomes of COVID-19 are generally mild, rare cases progress to MIS-C.
About the study In the present study, researchers used cohorts of children with a history of COVID-19 with and without MIS-C to profile the autoreactive antibodies and antibodies targeting SARS-CoV-2 using phage immunoprecipitation and sequencing , which has been extensively used in various diseases to identify novel autoantigens.
Logistic regression machine learning was used to identify the presence of differentially enriched peptides that distinguish MIS-C samples from at-risk control samples. The Kolmogorov-Smirnov test was used to identify statistically enriched autoreactivity. The validity of the findings was confirmed using an independent cohort comprising MIS-C patients and children severely affected by acute SARS-CoV-2 infection.
Study findings The antibody response in MIS-C patients was differentially reactive to SNX8 and a specific domain of the nucleocapsid protein of SARS-CoV-2 as compared to the antibody response of the at-risk controls. Furthermore, the SNX8 protein and this viral nucleocapsid region had remarkable biochemical similarities.
The SNX8 protein is functionally linked to the mitochondrial antiviral signaling pathway, and MIS-C is thought to be associated with an increased autoimmune response by SNX8 against tissues with high MAVS pathway expression. The researchers believe these results indicate similarities with other diseases, such as paraneoplastic autoimmune disease, where exposure to a novel antigen results in autoimmunity.
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