CD55 downregulation identifies a pathogenic CD4+ T cell axis linked to p38 MAPK signaling in rheumatoid arthritis

Abstract

CD4+ T cell dysfunction plays a critical role in the pathogenesis of rheumatoid arthritis (RA). In this study, we investigated the expression, phenotypic characteristics, and potential clinical significance of CD55, a membrane-bound complement regulatory protein, in peripheral blood CD4+ T cells from RA patients. Flow cytometric analysis revealed that CD55 expression was highest in naive CD4+ T cells and was significantly reduced in patients with early RA compared with healthy controls. Functionally, CD55+CD4+ T cells displayed enhanced production of IL-17, IL-21, and IL-22 following stimulation and exhibited reduced susceptibility to complement deposition. Transcriptomic analysis identified distinct molecular signatures associated with CD55 expression, which were further validated at the protein level, including increased expression of PAX5, CR2, and CD248 in CD55+CD4+ T cells. In addition, CD55 expression was inversely associated with p38 MAPK activation, suggesting a link between CD55 downregulation and aberrant T cell activation. Receiver operating characteristic analysis demonstrated that CD55+CD4+ T cell frequency possessed diagnostic value for distinguishing patients with early RA from healthy controls and primary Sjögren’s syndrome patients. Collectively, these findings identify CD55 as a marker of a distinct CD4+ T cell subset with altered functional and molecular characteristics and support its potential utility in the early diagnosis and differential diagnosis of RA.