CTLA-4 POLYMORPHISM ALONG WITH PROINFLAMMATORY CYTOKINES IN AUTOIMMUNE THYROIDITIS DISEASE.

OBJECTIVE: The aim: Evaluating serum concentration of IL-17 and IL-23 in autoimmune thyroiditis patient and control group along with the role of CTLA-4 rs3087243 gene polymorphism. PATIENTS AND METHODS: Materials and methods: A case control study was conducted in 30 HT (Hashimoto's thyroiditis), 30 GD (Graves' disease) who attended the consultant clinic for thyroiditis in AL-Diwaniyah teaching hospital and in 30 people as control group. Blood samples were processed for measurement of serum IL-17 and IL-23 using ELISA test. The second part used for DNA extraction then CTLA-4 polymorphism was detected by Allele - specific PCR assay. RESULTS: Results: The level of IL-17, and IL23 was highest in patients with Hashimoto's thyroiditis and Graves' disease, followed by control group and the difference was highly significant (p< 0.001; p< 0.001) respectively; however, the difference between patients Hashimoto's thyroiditis and patients with Graves' disease was not significant (p > 0.05; p > 0.05) respectively. There was no significant association between rs3087243 gene polymorphism and Hashimoto's thyroiditis (p> 0.05), no significant association between rs3087243 gene polymorphism and Graves' disease (p> 0.05). Moreover, there was no significant difference in rs3087243 genotypes frequencies between Hashimoto's thyroiditis and Graves' disease (p> 0.05). CONCLUSION: Conclusions: Serum IL-17 and IL-23 level have been linked with autoimmune thyroiditis disease, while CTLA-4 rs3087243 polymorphism seem to have no role in disease susceptibility in Iraqi population.

Circulating CTLA-4 levels and CTLA4 polymorphisms associate with disease condition and progression and hepatocellular carcinoma patients' survival in chronic hepatitis B virus infection.

BACKGROUND: CTLA-4 is involved in the immune dysfunction of hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC). This study analyzed the association of circulating CTLA-4 levels and CTLA4 polymorphisms with disease condition and progression in chronic HBV infection. METHODS: Serum CTLA-4 levels and CTLA4 rs231775 and rs5742909 polymorphisms were determined in patients with various HBV-related diseases [53 asymptomatic HBV carrier status (ASC), 147 chronic hepatitis, 130 cirrhosis and 102 HCC] and nearly a 10-year follow-up. RESULTS: Serum CTLA-4 levels were stepwisely increased from ASC, chronic hepatitis, cirrhosis to HCC and independently associated with HCC (OR 2.628, P < 0.001). HCC patients had lower frequencies of rs231775 genotype GA, genotype AA and allele A than ASC, chronic hepatitis and cirrhosis patients. Rs231775 genotype GG was independently associated with HCC (OR 2.324, P = 0.010) and higher CTLA-4 levels in patients with HBV infection. In the follow-up, higher baseline CTLA-4 levels and CTLA4 rs231775 genotype GG significantly associated with disease progression from chronic hepatitis to cirrhosis (OR 2.561, P = 0.011 and OR 2.799, P = 0.015, respectively) or from cirrhosis to HCC (OR 2.673, P = 0.008 and OR 2.097, P = 0.023, respectively) and with a shorter overall survival in HCC patients (HR 0.317, P = 0.018 and HR 0.682, P = 0.026, respectively). Rs5742909 had no significant association with CTLA-4 levels and disease progression. CONCLUSION: CTLA-4 levels and CTLA4 rs231775 polymorphism associate with the disease condition and progression and HCC development in chronic HBV infection and their determination may be used for monitoring disease progression and predicting patient prognosis.

Distribución de polimorfismos del gen del antígeno-4 del linfocito T citotóxico en población chilena con diabetes mellitus tipo 1 / Distribution of cytotoxic T lymphocyte antigen-4 gene polymorphisms in Chilean population with type 1 diabetes mellitus

Background: Cytotoxic T lymphocyte antigen-4 (CTLA-4) molecule is an important regulator of T cell activation involved in the down-regulation of immune response. Their polymorphisms +49 A/G and CT60 have been suggested to confer susceptibility to autoimmune endocrine disorders. The aim of this study was to determine the association of CTLA-4 gene polymorphisms with T1D in the Chilean population. We also wanted to study if the combined haplotypes of +49 A/G and CT60 had an impact on risk for T1D. Methods: To evaluate the impact of allelic variants CT60 and +49 A/G SNPs were studied in a Chilean population, including 248 T1D patients and 160 controls. Genotypes of both polymorphisms of CTLA-4 gene were determinate by PCR-restriction fragment polymorphism (PCRRFLP).Results: No statistical differences were observed when comparing patients with diabetes and controls for both CTLA-4 genotypes. However, the haplotype analysis between CT60 and +49 A/G showed an interesting combination of risk conformed by G*G combination with an OR of 1.648 [1.19- 2.28], (p = 0.002). Conclusions: The G*G haplotype could be a risk marker in patients with T1D in Chilean population.