Autoantibodies to type I interferons in patients with systemic mastocytosis
Journal of Allergy and Clinical Immunology: Global(2024)
摘要
Background
Autoantibodies to type-I interferons (IFN-I) have been identified in association with a variety of inflammatory and autoimmune diseases. IFN-I’s have demonstrated inhibitory effects on mast cell proliferation and degranulation. Systemic mastocytosis (SM) is a disease characterized by increased mast cell burden and mediator release. Whether autoantibodies to IFN-I are present in the serum of patients with SM and if so, whether they correlate with characteristics of disease, is unknown.
Objective
The purpose of this study was to determine whether autoantibodies to IFN-I’s are observed in the sera of patients with SM and if so whether they correlate with biomarkers of disease severity.
Methods
We analyzed sera from 89 patients with SM for concentrations of autoantibodies to IFN-I using a multiplex particle-based assay and signal-neutralization capacity using a STAT1 activity assay and compared these measurements to those of a database of 1284 healthy controls.
Results
Our cohort was predominantly female (57.3%) with a median age of 56 years, within which 13 produced autoantibodies to IFN-β, 3 to IFN-ω, and 0 for IFN-α. Of these, no patient serum demonstrated signal-neutralization. Neither concentration of autoantibodies nor signaling inhibition measurements correlated with tryptase concentrations or D816V allele burden.
Conclusion
Although a small sub-population of patients with SM have autoantibodies to IFN-I’s, there was no correlation between autoantibody production and signaling inhibition. These data are consistent with the conclusion that autoantibodies to IFN-I do not play a significant role in the pathogenesis or severity of systemic mastocytosis.
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关键词
Autoantibodies,type-I interferons,cytokines,mastocytosis,mast cell,inflammatory,autoimmune,COVID-19
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