CD 160 molecules and IL28 B genotypes in diabetic and non diabetic chronic hepatitis C patients

Background and Aim: Despite the close relationship between hepatitis C viral infection (HCV) and diabetes mellitus type 2 (DM2), the underlying mechanism that links diabetes and HCV infection remains conjectural. During chronic hepatitis C disease, key inhibitory molecules including CD160 are up-regulated with different kinetics on CD8 cytotoxic T lymphocytes. There are two different opinions regarding the function of CD160 molecules, the first opinion suggested that the expression of CD160 on CD8 cytotoxic T cell contribute to the exhaustion and failure of immune responses, whereas the other opinion defined CD160 molecule as modulators and regulators of immune responses. Thus, we aimed to assess the pattern of expression and the role of CD160 molecules in the development and controlling of HCV associated diabetes. Also, a little of known about the genetic control of CD160 signaling pathway between T lymphocytes and antigen presenting cells. Recently, IL-28B gene polymorphisms were identified as a genetic predictor for progression of HCV and the effectiveness of antiviral therapy. IL28B polymorphisms include C/C, C/T and T/T genotypes, C/C genotype is considered as a good predictor of disease progression and therapy responses while T alleles groups were associated with bad prognosis and less response to therapy. We aimed to clarify the link between a triad, CD160 molecules, T lymphocytes immune responses and IL28B genotypes during HCV associated diabetes. Patients & Methods: This cross sectional study was conducted at Al-Zahraa University Hospital from June 2011 to January 2012. An informed consent was obtained from patients. The study included fourteen diabetic chronic hepatitis C (HCV) patients, fourteen non-diabetic HCV patients (without decompensated liver or hepatocellular carcinoma) and twelve healthy control subjects. The selection of HCV patients depends upon seropositive anti-HCV confirmed by positive HCV-RNA-PCR. Also, the exclusion of patients with decompensated liver disease or hepatocellular carcinoma was achieved via questionnaire, clinical examination, pelviabdominal ultrasonography and routine laboratory investigations. The diabetic HCV patients were identified in the presence of documented hypoglycemic medications or fasting blood sugar greater than 140 mg/dL on two occasions. Using flow cytometry, the patients and control groups were investigated for the expression of CD160 molecules on CD8 T lymphocytes. Using real time PCR, the diabetic and non-diabetic HCV patients were evaluated for the frequency of IL-28B genotypes. In addition, the diabetic HCV patients were estimated for glycosylated hemoglobin (Hb A1C) using high performance liquid chromatography (HPLC). Results: The diabetic and non-diabetic HCV patients showed statistically significant increase in CD160% as matched to control group. Importantly, theCD8 cytotoxic T cells of diabetic HCV group displayed higher expression of CD160% as compared to non-diabetic group. Also, we observed significant negative correlation between the frequency of CD160 molecules and the mean value of HbA1C in diabetic HCV group. As regard IL-28B polymorphisms, our result showed higher frequency of C/C genotype in diabetic HCV patients, whereas non-diabetic HCV group showed higher frequency of C/T genotype. Interestingly, our data showed an association of favorable genotype C/C with higher frequency of CD160 molecules as matched to both T alleles genotypes groups. Conclusion: we concluded that CD 160 molecules up regulation on cytotoxic CD8 T cells occur as a consequence of exaggerated immune responses and vigorous secretion of proinflammatory cytokines. Also, we clarified that the over expression of CD160 in tandem with IL28B C/C genotype is considered as a good predictor of disease progression and antiviral treatment response. In addition, we suggested the involvement of IL28 B gene in controlling T cell immune responses including CD160 signaling via HLA class-1 gene. Importantly, we confirmed the modulatory and regulatory role of CD160 molecules in controlling of HCV associated diabetes. (Nahla M Abd-Elaziz and Karima Y Ahmed. CD 160 molecules and IL28 B genotypes in diabetic and non diabetic chronic hepatitis C. Life Sci J 2013;10(1):129-137) (ISSN:1097-8135). http://www.lifesciencesite. com. 19