CD 160 molecules
CD 160 molecules and IL28 B genotypes in diabetic and non diabetic chronic hepatitis C patients
Nahla M Abd-Elaziz1 and Karima Y Ahmed2
Department of Clinical Pathology1 and Internal Medicine2, Faculty of Medicine for Girls,Alazhar University, Egypt. firstname.lastname@example.org
Abstract 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 remain 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 was 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 March 2012. An informed consent was obtained from patients. The study included twenty diabetic chronic hepatitis C (HCV) patients, twenty non-diabetic HCV patients (without decompensated liver or hepatocellular carcinoma) and twenty 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
Keywords: CD160, IL28B, HCV, diabetes Full Text 19