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. [email protected]
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