A large-scale profiling study of immune-coagulation associations in rheumatoid arthritis

To systematically profile associations between immunological markers and coagulation parameters in patients with rheumatoid arthritis (RA), and to evaluate the reproducibility and independence of these associations from demographic and inflammatory factors.

We conducted a retrospective cross-sectional analysis of 1,656 hospitalized patients with RA. Associations between immunological markers (immunoglobulin G [IgG], immunoglobulin A [IgA], immunoglobulin M [IgM], rheumatoid factor [RF], anti-citrullinated protein antibodies [ACPA], C3, and C4) and coagulation parameters (international normalized ratio [INR], prothrombin time [PT], PT activity, activated partial thromboplastin time [APTT], D-dimer, and fibrinogen) were assessed using multivariable linear regression adjusted for age, sex, erythrocyte sedimentation rate, and high-sensitivity C-reactive protein. The cohort was divided into exploratory and validation subsets based on the median admission date. Robustness was examined using reduced-variable and principal component analysis-based sensitivity models.

Thirteen immune-coagulation associations were reproducibly identified across exploratory and validation cohorts. IgG showed coordinated associations with multiple coagulation parameters, including positive associations with INR, PT, APTT, and D-dimer, and negative associations with PT activity and fibrinogen. RF and ACPA exhibited inverse associations with APTT and fibrinogen, while complement components C3 and C4 were positively associated with fibrinogen levels. These patterns remained stable across sensitivity analyses, supporting the reproducibility of immune-coagulation coupling at the laboratory biomarker level.

This large-scale profiling study delineates reproducible and internally validated associations between immunological markers and coagulation parameters in RA, revealing a structured immune-coagulation landscape at the laboratory level. Rather than implying clinical outcomes, these findings provide a reference framework to contextualize immune-coagulation interactions and support hypothesis-driven longitudinal or mechanistic investigations.