Evidence of molecular mimicry in multisystem inflammatory syndrome in children (MIS-C)

Multisystem inflammatory syndrome in children (MIS-C) is a severe, post-infectious sequela of SARS-CoV-2 infection, yet the pathophysiological mechanism connecting the infection to the broad inflammatory syndrome remains unknown. Here we leveraged a large set of MIS-C patient samples (n=199) to identify a distinct set of host proteins that are differentially targeted by patient autoantibodies relative to matched controls. We identified an autoreactive epitope within SNX8, a protein expressed primarily in immune cells that regulates an antiviral pathway associated with MIS-C pathogenesis. In parallel, we also probed the SARS-CoV-2 proteome-wide MIS-C patient antibody response and found it to be differentially reactive to a distinct domain of the SARS-CoV-2 nucleocapsid (N) protein relative to controls. This viral N region and the mapped SNX8 epitope bear remarkable biochemical similarity.  Furthermore, we find that many children with anti-SNX8 autoantibodies also have T cells cross-react..., Patients
Patients were recruited through the prospectively enrolling multicenter Overcoming COVID-19 and Taking on COVID-19 Together study in the United States. The study was approved by the central Boston Children’s Hospital Institutional Review Board (IRB) and reviewed by IRBs of participating sites with CDC IRB reliance. A total of 292 patients were enrolled into 1 of the following independent cohorts between June 1, 2020 and September 9, 2021: 223 patients hospitalized with MIS-C (199 in the primary discovery cohort, 24 in a separate subsequent validation cohort), 29 patients hospitalized for COVID-19 in either an intensive care or step-down unit (referred to as severe acute COVID-19 in this study), and 45 outpatients (referred to as “at-risk controls” in this study) post-SARS-CoV-2 infections associated with mild or no symptoms. The demographic and clinical data are summarized in Table I, Extended Data Table 1, and Extended Data Table 2. The 2020 US Centers for Disease Control and ..., , # Evidence of molecular mimicry in multisystem inflammatory syndrome in children (MIS-C)

## Description of the data and file structure

This Dryad submission contains PhIP-Seq results for two distinct T7 bacteriophage libraries, one for identifying autoantibodies targeting human proteins, and one for identifying antibodies targeting SARS-CoV-2 proteins. Each library was run on MIS-C patients (n=199) and
at-risk pediatric controls (n=45).

For human proteome results, all data is formatted as a fold-change over mock-IP. For all SARS-CoV-2 results, all data is formatted as a fold-change over pre-COVID.

There are therefore 4 separate CSV files:

* Human Proteome MIS-C patients
* Human Proteome at-risk controls
* SARS-CoV-2 Proteome MIS-C patients
* SARS-CoV-2 Proteome at-risk controls

Each individual is a column. For the Human Proteome library, each row represents the summed values from each peptide corresponding to a given gene. For the SARS-CoV-2 Proteome library, each row repr...