Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized
by joint inflammation, cartilage destruction, and disability. Activation of the nucleotidebinding leucine-rich repeat receptor (NLR) family pyrin domain- containing 3 (NLRP3)
inflammasome, and its adaptor protein PYCARD (ASC) plays a crucial role in
pathogenesis by promoting the release of interleukin-1β and IL-18, and pyroptotic cell
death. Genetic variations such as the NLRP3 rs4612666 single-nucleotide polymorphism
(SNP) may influence the activity and susceptibility to RA. Understanding the interplay
between serum PYCARD levels and NLRP3 gene polymorphisms could provide insights
into RA prognosis. Aim: This study aimed to investigate the association between serum
PYCARD levels and NLRP3 rs4612666 polymorphism with RA susceptibility and disease
activity. Methodology: This comparative cross-sectional study included 21 RA patients
and 21 age- and sex-matched healthy controls. Serum PYCARD levels were quantified
using Enzyme-Linked Immunosorbent Assay. Genotyping of the NLRP3 rs4612666
polymorphism was performed using Polymerase Chain Reaction and restriction
fragment length polymorphism analysis. Results: Serum PYCARD levels were
significantly higher in RA patients compared to controls and positively correlated with
disease activity and inflammatory markers. The NLRP3 rs4612666 CC genotype was
associated with increased RA susceptibility and higher disease activity scores, while the
TT genotype appeared protective. Multivariate analysis revealed that serum PYCARD
and the CC genotype are potential predictors of RA and its activity. Conclusion:
Elevated serum PYCARD and NLRP3 rs4612666 SNP are strongly associated with RA
susceptibility and disease activity. These markers may serve as tools for early diagnosis,
prognosis, and personalized therapy in RA.