Defects in the Zeta Chain Expression (ζ) in a Group of Patients with SLE, Scleroderma and Late-onset Arthritis, Colombia 2014

Abstract

Introduction: Systemic Lupus Erythematosus (SLE), Scleroderma and late-onset arthritis are autoimmune inflammatory diseases (EIA) characterized by autoantibody production and presence of abnormal T cells which generate defective immune response. The abnormal expression of key signaling molecules in the defective function of T-lymphocytes plays a significant role in the pathogenesis of autoimmune disease. The T-cells exhibit numerous abnormalities TCRζ1 signaling complex, these aberrations result in altered expression of cytokines and some biochemical events involved in the expression of surface molecules. Defects in the complex may be associated TCRζ to steroids used in autoimmune disease patients due to their powerful anti-inflammatory activity and immunosuppressive properties. The synthetic corticosteroids such as examethasone inhibit the transcriptional activity of some factors such as NFKB and AP-1, which regulate the synthesis of certain cytokines and could be involved in the TCRζ synthesis. Material and Methods: A case-control study, with a 1:1 ratio of cases and controls (13:13). Cases were patients with active autoimmune disease (6 patients with SLE, 5 patients with scleroderma and 2 patients with lateonset arthritis), who have not started treatment with corticosteroids. Controls were patients with no autoimmune disease. The diagnosis was made by the criteria established by the American College of Rheumatology for patients with SLE, scleroderma and late-onset arthritis. A 10 mL sample was obtained by venipuncture whole blood. Total RNA was extracted and RT-PCR was performed using a set of primers flanking a region of 138 base pairs involving exons 2, 3 and 4 of the ζ chain. Results: The values of Z chain amplification showed significant differences in patients with autoimmune disease (0.8214 } 0.1787, med = 0.7368) compared with the control group (0.9225 } 0.1272, med = 0.9830) (p = 0.045, Mann-Withney non-parametric one tailed exact test). Conclusion: We observed a reduced level of in the zeta chain expression in T cells in patients with autoimmune disease without use of corticosteroids.

Keywords

• ζ Chain Corticosteroids
• T-Cells
• Splicing
• Lupus Erythematosus (SLE)
• T-Cell Receptor (TCR)
• IgG Fraction Crystallizable (Fcγ)
• Cytokines