Tumor necrosis factor alpha-induced protein3 rs;10499194 polymorphism enhances presepsin and sCD64 accuracy in differentiating infection from rheumatoid arthritis flare.

Differentiating concurrent general microbial infection from disease flare in Rheumatoid Arthritis (RA) remains challenging. This study evaluated the diagnostic performance of Presepsin and soluble cluster of differentiation 64 (sCD64), and their association with the tumor necrosis factor-alpha-induced protein 3 (TNFAIP3) rs10499194 polymorphism. This case-control study included 90 participants: 30 normal controls, 30 RA without infection, and 30 RA with infection. Serum Presepsin and sCD64 were measured by ELISA, and gene detection for SNP TNFAIP3 rs10499194 (C>T) was performed using the tetra-primer amplification refractory mutation system polymerase chain reaction. Presepsin and sCD64 levels were significantly elevated in the RA with infection group compared to uninfected RA patients and controls (p<0.001). Presepsin (area under the curve, AUC=0.910) and sCD64 (AUC=0.870) outperformed conventional markers (CRP, ESR) in diagnosing infection. The combined biomarkers yielded an AUC of 0.956. The TNFAIP3 T allele was significantly associated with RA susceptibility (OR=2.87, p=0.028). Furthermore, T allele carriers exhibited a dose-dependent, significant increase in both Presepsin (p=0.005) and sCD64 (p=0.013) levels, particularly during infectious episodes. In conclusion, Presepsin and sCD64 are highly accurate biomarkers for distinguishing infection from RA flares. The TNFAIP3 rs10499194 T allele not only increases RA risk but also amplifies the innate immune response during concurrent infections.