Comparative characteristics of immune answers indicators depending on the replicative activity and genotype of hepatitis c virus
DOI:
https://doi.org/10.15587/2313-8416.2015.48200Keywords:
acute hepatitis С, chronic hepatitis С, cytokines, subpopulations of lymphocytes, genotypeAbstract
Aim. To analyze the character of changes and disorders of immune system with the help of complex study of indicators of cellular and humor section of immunity, cytokine status in patients with HCV-infection taking into account the replicative activity, genotype of virus and to formulate the possible causes of chronization.
Methods. There were examined 155 patients with HCV-infection. An acute hepatitis C AHC) was fixed in 23,9 %, chronic hepatitis C (CHC)– in 76,1 %, 18–70 years old. Among examined patients with AHC and CHC prevailed men (67,6 and 72 % respectively). Diagnosis was set on the base of clinic and amnestic, epidemiologic, laboratory and instrumental data. Epidemiologic verification of diagnosis was realized by detection the specific serologic markers of HC (anti-HCV (sum), anti-HCV IgM and Ig G, anti-HCV core and anti-HCV NS-3, NS-4, NS-5) in blood serum using ELISA method. Molecular and genetic studies that included definition of replicative activity of HCV evaluated on the base of detection of RNA HCV in blood serum using the qualitative PCR method were carried out in 126 patients (31 with AHC and 95 with CHC). At the same time RNA of HCV was detected in peripheral blood in all (31) patients with AHC and in 74 (77,89 %) patients with CHC. Using the method of restriction analysis we carried out the genetic typing of HCV in 90 patients with AHC and 60 with CHC. We carried out the comparative characteristics of the content of immunologic indicators in 45 (75 %) patients with CHC with positive and 15 (25 %) patients with negative results of PCR-study (polymerase chain reaction) of HCV RNA in blood. For detection of regularities of changes of immune status depending on virus genotype there was carried out the comparative assessment of the content of immunologic indicators in patients with AHC and CHC with the most widespread genotypes of HVC– 1b and 3a. Immunologic studies included the definitions of the main subpopulations of lymphocytes (CD3+, CD4+, CD8+, CD16+, CD20+, CD25+), the general number of immunoglobulins Ig A, M, G, CIC (circulating immune complexes) and cytokine levels (CK) (TNF-α, ІL-2, ІL-4, ІL-10, IFN-γ) in blood serum. The features of immune status with definition of qualitative and quantitative content of its indicators were analyzed depending on presence of molecular and genetic markers of replication activity and HCV genotype in blood of patients
Results. RNA of НСV were detected in peripheral blood of patients with AHC (100%) and CHC (77,89 %). HCV 1b genotype turned out the most widespread among patients with both AHC 50%), and CHC (43,3 %). 3а genotype – in 30 % and 38,3 % patients with AHC and CHC respectively took the second place. In patients with AHC the combination 1b/3а and 2 genotypes of HCV were equally often – in 10 % of patients respectively. The combination 1а/3а and isolated 1а genotype was not detected in patients with AHC. In patients with CHC the combination 1b/3а was detected in 6,7 %. 1а/3а and 3а genotypes combinations were registered equally often (5,0 %). 2 genotype was observed rather random – in 1,7 % patients with CHC. In patients with НCV(RNA+) in blood the relative and absolute number of lymphocytes with phenotypes CD3+; CD4+; CD16+; CD25, ІRІ were probably lower compared with analogous indicators in patients with negative results of PCR (p<0,05). On the contrary the content of circulating immune complexes CD20+- lymphocytes, concentration of Ig M and Ig G were probably higher in blood of patients with CHC with positive result of HCV-RNA compared with ones in patients with negative result of HCV RNA study (p<0,05). The probable (p<0,05) increase of CD3+; CD4+ indicators, CD16+; CD25+ circulating complexes were intrinsic for patients with AHC and 3а genotype compared with analogous indicators in patients with CHC and 1b genotype. The content of CD20+-lymphocytes, circulating immune complexes, ІgM, ІgG, was on the contrary probably higher in patients with 1b genotype as opposed to such indicators in patients with 3а genotype. At chronic clinical course of HCV-infection there was observed an analogous dependence of content of immunologic indicators from detected genotype. In patients with 3а genotype the mean indicators CD3+; CD4+; CIC, CD16+, CD25+ were probably higher than the respective ones in patients with 1b genotype. In patients with CHC and HCV 1b genotype indicators CD20+, circulating immune complexes (CIC); Іg M; Ig G probably exceeded analogous indicators in patients with HCV 3a genotype (p<0,05). The comparative analysis of cytokine status in patients with CHC with positive and negative result of the study of presence of HCV-RNA in blood of patients with CHC demonstrated that in the period of replicative activity of HCV (RNA+) the level of IFN-γ and IL-2 turned out probably lower compared with ones in patients with negative result of the study of HCV-RNA (RNA-) (p<0,05). On the contrary in patients with PCR + the levels of TNF-α, IL-4 and IL-10 were reliably higher compared with ones in patients with the lack of replicative activity. In the blood serum of patients with AHC of 3а genotype of concentration IL-2 and IFN-γ were probably higher compared with analogous indicators in patients with 1b genotype (p<0,05). An opposite regularity was retraced at analysis of TNFα, IL-4 and IL-10 data, its levels in patients with 3a genotype were probably lower than indicators in patients with 1b one (p<0,05). ІL-2 and IFN-γ concentrations in patients with 1b genotype were essentially decreased compared with patients with 3а genotype (p<0,05). At the same time the TNF-α, IL-4 and IL-10 levels in patients with 1b genotype considerably exceeded the analogous indicators in patients with 3а genotype (p<0,05).
Conclusions. At AHC and CHC there were observed the same directional dependence of the content of immunologic indicators from detected genotype. So in patients with AHC and CHC with 3а genotype CD3+, CD4+, ІRІ, CD16+, CD25+, ІL-2 and IFN-γ levels were probably higher and CD20+, CIC, Іg M, Ig G, TNF-α, IL-4 and IL-10 decreased compared with respective indicators in patients with НCV 1b genotype. So in patients with 3а genotype indicators that characterize Тh1-effector potential were probably higher that testifies an activation of cellular immune answer. In patients with 1b genotype there was observed a depression of cellular section of immunity and by-turn the higher content of indicators that characterize an activity of Тh2-effectors that leads to switching of immune answer to humor Тh2-answer
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