What does this research mean for the field?

Helper T-lymphocyte subset imbalances and IL-6R-mediated signaling increase the risk of atrial fibrillation, whereas elevated IL-18 gene expression provides a protective effect. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

January 1, 2026Cardiovascular TherapeuticsOpen Access

Analysis of the Correlation Between Helper T‐Lymphocyte Subsets and Atrial Fibrillation: An Observational and Mendelian Randomization Study

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Why the study?

Evidence suggests immunological diseases may contribute to atrial fibrillation, but the influence of T-lymphocyte subsets and immunomodulatory drug targets on AF risk required combined observational and genetic investigation.

Do specific T-lymphocyte subsets and immunomodulatory drug targets influence the risk of atrial fibrillation?

Structured PICO

Do specific T-lymphocyte subsets and immunomodulatory drug targets influence the risk of atrial fibrillation?

Population

302 patients with atrial fibrillation and 183 healthy controls (observational cohort), plus genetic datasets for Mendelian randomization

Intervention

T-lymphocyte subsets and immunomodulatory drug targets (IL-6R, IL-18)

Comparator

Healthy controls (observational); genetic variants (Mendelian randomization)

Outcome

Atrial fibrillation risk

Immune dysfunction, particularly involving T-lymphocyte subsets and the IL-6R signaling pathway, is associated with an increased risk of atrial fibrillation.

Implication

T-cell subset alterations may flag higher AF risk; leaves open whether immunomodulatory targets alter incidence.

Abstract

Background Atrial fibrillation (AF) is the predominant arrhythmia. Growing evidence indicates that immunological diseases may play a role in its development. This study combined observational and genetic analyses to investigate how T‐lymphocyte subsets and immunomodulatory drug targets influenced AF risk. Methods and Results This study retrospectively analyzed T lymphocyte subsets in 302 AF patients and 183 healthy controls. After balancing covariates via 1:1 propensity score matching, multivariate regression revealed AF patients had significantly higher absolute counts of Th1 and Th17 cells, and higher Th1/Th2 and Th17/Treg ratios ( p < 0.05). A subsequent two‐sample Mendelian randomization (MR) analysis, which assessed 731 immune traits and included drug‐target MR, established causal relationships. It showed that increased counts of CD4 + CD8dim T cells (OR = 1.03, p = 0.002) and IgD − CD38dim B cells (OR = 1.06, p = 0.0003) elevated AF risk. Furthermore, IL‐6R‐mediated CRP elevation increased AF risk (OR = 1.33, p = 5.18E‐7), whereas higher IL‐18 gene expression was protective (OR = 0.95, p = 0.036). Conclusion Immune dysfunction, especially T lymphocyte subsets, is a risk factor for the development of AF. The IL‐6R signaling pathway may be a potential target for AF prevention, whereas the use of IL‐18 inhibitors may increase the risk of AF.