Work

Macrophage Activation Syndrome–Associated Proteins and Enhanced Interferon‐γ Responsiveness in the Plasma Proteome of Patients With Multisystem Inflammatory Syndrome in Children in a Pretreatment Replication Single‐Center Cohort

Year: 2026

Type: article

Abstract: OBJECTIVE: Multisystem inflammatory syndrome in children (MIS-C) is a rare hyperinflammatory syndrome that follows SARS-CoV-2 infection. Prior plasma proteomic analysis from a 2020 cohort of patients with MIS-C at our center revealed a profile characterized by thrombotic microangiopathy (TMA), macrophage activation syndrome (MAS)-associated proteins, and dysregulated interferon-γ (IFNγ) responses. However, a limitation of that study was that samples were often acquired after treatment. The objective of this study was to identify plasma proteomic signatures that uniquely define MIS-C versus other viral syndromes unconfounded by treatment effects in an independent cohort. METHODS: Plasma proteomics was performed using the Olink Explore HT platform on plasma from patients enrolled at emergency department admission with suspected MIS-C (final diagnoses N = 12 MIS-C, N = 30 other viral syndromes). Plasma autoantibody analysis was performed using a custom microbead-based protein array. RESULTS: Consistent with findings in the 2020 cohort, TMA- and MAS-associated proteins were more highly expressed, and there was a higher CXCL9 response to IFNγ in MIS-C compared to viral infection. In contrast to the 2020 cohort, patients with MIS-C did not have lower expression of the IFNγ suppressive protein TRIM21. On reanalysis of the 2020 cohort, only patients who received intravenous Ig (IVIg) treatment before sampling had low TRIM21 (also known as Ro52/SSA). IVIg recipients also had anti-Ro52 autoantibodies. CONCLUSION: We have validated several unique features of the plasma proteome of patients with MIS-C first identified in 2020. Discrepant TRIM21 expression in these two cohorts is due to anti-Ro52 autoantibodies in IVIg-treated patients. These data support the use of plasma cytokine profiling to rapidly diagnose MIS-C.

Source: ACR Open Rheumatology

DOI: 10.1002/acr2.70181