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Ma, C. S.

Publications and source records attributed to Ma, C. S..

2 recordsLinked to original sources

Longitudinal Plasma Proteome Changes Before and After Catheter Ablation in Atrial Fibrillation

BackgroundProteins in human plasma serve as critical markers for predicting disease risk and guiding therapeutic development. Current prediction models for atrial fibrillation (AF) largely rely on electronic health records; however, the plasma proteome of patients with AF reflects key biological processes, including inflammation, that are not captured by clinical variables alone. Circulating inflammatory mediators contribute to electrical and structural remodelling in the atria, thereby sustaining the AF phenotype. Identification of plasma proteins associated with AF may therefore improve understanding of the inflammatory and other biological processes underlying AF pathophysiology. ObjectiveIn this study, we profiled the plasma proteome of patients with paroxysmal AF (pxAF), persistent AF (persAF), and non-AF controls using Olink assay technology. MethodsPlasma samples from 30 individuals were analysed with the Olink Reveal panel. Differential expression analysis of normalised protein expression (NPX) values was performed between groups, with differentially expressed proteins (DEPs) defined by P < 0.05. ResultsWe identified 87 DEPs in pxAF and 107 DEPs in persAF compared with controls. From these, we shortlisted 11 candidate proteins that were upregulated in persAF at baseline and showed reduced expression 12 months after catheter ablation. This subset of proteins is implicated in the regulation of inflammation (CCL23, CXCL10, IL33), metabolism (ALDH3A1, NDUFS6), cell-matrix adhesion (AFAP1L1, LGALS7, SPOCK1), and physiological signalling (NOS1, PROK1, PTH). ConclusionCollectively, these plasma proteins highlight systemic molecular mechanisms contributing to AF pathogenesis and represent potential AF-specific biomarkers warranting further investigation in larger clinical cohorts and mechanistic studies.

molecular biology↗

Overactive STAT3 drives accumulation of disease-associated CD21low B cells

Dysregulated STAT3 signalling is correlated with antibody-mediated autoimmunity and B- cell neoplasia, but its effect on B cells is underexplored. Here we address this in children with STAT3 gain-of-function (GOF) syndrome and in mice with STAT3T716M, the most common STAT3 GOF syndrome human mutation, or STAT3K658N, a dimerization interface mutation responsible for STAT3 GOF syndrome in two children. The main B cell consequence of overactive STAT3 was accumulation of CD19high CD21low atypical memory B cells in humans and of CD21low CD23low B cells in mice resembling age-associated B cells expressing T-bet, CD11c and plasma cell differentiation genes. Overactive STAT3 within B cells increased expression of many genes in the B cell receptor and T cell help pathways, increased the tolerogenic receptor CD22, but opposed B cell tolerance checkpoints and increased formation of T-bet+ B cells upon BCR and CD40 stimulation. These results reveal overactive STAT3 as a central driver of a key class of disease- associated B-lymphocytes in humans and mice.

immunology↗