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Tumor necrosis factor alpha-induced protein3 rs;10499194 polymorphism enhances presepsin and sCD64 accuracy in

Fatima H Mohammed1, Dheyaa S A Al-Jameel1, Ali A Hamzah2

  • 1Department of Microbiology, Faculty of Medicine, Jabir Ibn Hayyan University for Medical and Pharmaceutical Sciences, Najaf, Iraq.

The Egyptian Journal of Immunology
|July 14, 2026
PubMed

Insights

New biomarkers Presepsin and soluble CD64 effectively distinguish microbial infections from Rheumatoid Arthritis flares. The TNFAIP3 gene variant also impacts RA susceptibility and infection response.

Area of Science:

  • Immunology
  • Clinical Diagnostics
  • Genetics

Background:

  • Differentiating concurrent microbial infections from Rheumatoid Arthritis (RA) flares is clinically challenging.
  • Existing diagnostic markers like CRP and ESR have limitations in this context.
  • The role of specific genetic polymorphisms in RA susceptibility and infection response requires further investigation.

Purpose of the Study:

  • To evaluate the diagnostic performance of Presepsin and soluble cluster of differentiation 64 (sCD64) in distinguishing infection from RA flares.
  • To assess the association between the TNFAIP3 rs10499194 polymorphism and RA susceptibility and infection response.
  • To explore the combined diagnostic utility of Presepsin, sCD64, and genetic factors.

Main Methods:

  • A case-control study involving 90 participants: 30 normal controls, 30 RA without infection, and 30 RA with infection.
  • Serum Presepsin and sCD64 levels were quantified using ELISA.
  • TNFAIP3 rs10499194 (C>T) genotyping was performed using tetra-primer ARMS-PCR.

Main Results:

  • Presepsin and sCD64 levels were significantly elevated in RA patients with infection compared to controls and RA patients without infection (p<0.001).
  • Presepsin (AUC=0.910) and sCD64 (AUC=0.870) demonstrated superior diagnostic accuracy over CRP and ESR for infection detection; combined AUC was 0.956.
  • The TNFAIP3 T allele was associated with increased RA susceptibility (OR=2.87, p=0.028) and correlated with higher Presepsin and sCD64 levels in T allele carriers, especially during infections.

Conclusions:

  • Presepsin and sCD64 are highly accurate biomarkers for differentiating infection from RA flares.
  • The TNFAIP3 rs10499194 T allele is linked to RA susceptibility and exacerbates innate immune responses during infections.
  • These findings offer improved diagnostic strategies for RA patients with suspected concurrent infections.

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