LAUSR

Background Advances in understanding the pathogenesis of RA support the contribution of T cells in the disease process through the recognition of the arthritogenic antigen (Ag) and maintenance of chronic inflammatory response [1]. Previous gene association studies have demonstrated that CD247 gene expressions are associated with a variety of autoimmune disease. As regard Rheumatoid Arthritis (RA), this relationship has not been fully clarified yet. Objectives We aimed to evaluate the T-cell receptor-CD3 zeta chain (TCR-CD3 ζ) gene expression profile in a cohort of patients with RA. Methods A case-control study on 150 consecutive RA patients diagnosed according to 2010 ACR/EULAR criteria and 150 matched healthy controls without family history of RA or other autoimmune diseases. RA patients with other autoimmune diseases, viral hepatitis B or C, malignancy or hematological disorders were excluded from the study. All participants were subjected to history taking, clinical examination, assessment of disease activity (in RA patients) using DAS-28 and HAQ, routine laboratory investigations, inflammatory markers level, serological tests, as well as molecular analysis for TCR-CD3ζ mRNA expression by quantitative real-time polymerase chain reaction. Results TCR-CD3ζ gene expression was significantly lower in RA cases than in healthy controls (p<0.05) (Table 1). Expression of TCR-CD3ζ revealed a significant negative correlation with RA disease duration, RF, and ESR (p<0.05) in RA cases. The level of TCR-CD3ζ also showed a significant lower expression in +ve RF patients than in –ve RF patients (p<0.05). The AUC of TCR-CD3ζ level showed a moderate level of accuracy (AUC = 0.840, p=0.025) ( Figure 1), and the calculated cutoff value (≤ 0.077) can precisely discriminate subjects with RA from those without RA with 93.5% sensitivity and 75% specificity( Table 2 ). Table 1 Comparison between RA cases and control group as regard CD247 (mRNA levels for TCR-CD3ζ gene expression) TCR-CD3ζ RA cases (n=150) Healthy Controls (n=150) Test of sig. P Min. – Max. 0.037– 12.467 0.034- 11.314 Z=-3.047* 0.002* Mean ± SD. 0.663 ± 1.90 0.816 ± 1.64 Median (Q1-Q3) 0.178 (0.109-0.314) 0.315 (0.198-0.922) Z: Z-score of Mann-Whitney test *: Statistically significant at p≤0.05Table 2 Analysis of ROC curve for TCR-CD3ζ level as a predictor of RA (high RF) Variable Cutoff point(ng/ml) AUC P Sensitivity (%) Specificity (%) PPV NPV Accuracy (%) TCR-CD3ζ ≤ 0.077 0.840* 0.025** 93.5 75.0 78.9 92.0 84.3 AUC: Area under the curve *AUC ≥ 0.5 ** Statistically significant at p ≤ 0.05 PPV: Positive Predictive Value NPV: Negative Predictive ValueFigure 1 ROC curve for CD247 (TCR-CD3ζ) level as a predictor of Rheumatoid arthritis Conclusion Our results demonstrated a lower expression of TCR-CD3ζ in RA patients than in healthy controls. We suggested that CD247 gene down-regulation might contribute in the susceptibility to RA and help understanding the mechanisms responsible for deficient T-cell responses in RA patients. Reference [1] Wfeyand CM, Gaoronzy JJ. Pathogenesis of rheumatoid arthritis. Med Clin North Am 1997; 81:29–55. Disclosure of Interests None declared