Primary Study On Clinical Significance Of α/β Interferon Receptors In PBMC, Hepatic Tissue And HBV Genotypes

Alpha interferon (IFN) consists of amino acid which among other functions plays an important role in the anti-proliferation and immunoregulation activities. These actions are mediated through alpha/beta IFN receptor (alpha/beta IFNR). IFN share the same path through the common intracellular signaling. But its severe side-effect, high prices and low sustained response(SR) are the main obstacle of its wide use. So people made great effort to find the predicted factors for IFN's SR in order to select the right way to anti-virus. Some study has shown that the follow factors can predict the IFN's SR, such as the grade inflammation of the hepatic tissues, HBV DNA levels in the serum, the baseline ALT levels and so on.IFN demonstrates antiviral activity by binding to receptors on the cell surface. And then it actives the signal pathway, produces anti-virus protein . The α/β IFN use the common type I IFNR , while the Y IFN use the type II IFNR. The human type I IFNR is composed of at least two subunits, termed α and β (also designated as IFNAR1 and IFNR2,respectively).The β subunits has two transmembrane forms β short(βs) and β long( β1),both of which can bind IFNs with low affinity. High affinity binding occurs when both α and either form of β are coexpressed; Each chain also associates with specific Jak kinase that is required for signaling;the α chain docks Tyk2,whereas the long β subunits interacts with Jakl.Oligomerization of the receptor subunits occurs upon ligand binding and induces intra- and intermolecular phophorylation of the Jak kinases.The activated kinases are then thought to phosphorylate the receptor chains and Statl,2,and 3.The Stat molecules then homo- or heterodimerize and migrate to the nucleus where they stimulate transcription of the IFN-inducible genes. The short and soluble forms can bind IFNRand then inhibit the signal transduction pathway because of a lack of intracellular part. And the short form has low levels in serum so the soluble receptor was suspected to be responsible in part for the IFN-inhibiting activity.IFNR can express in many tissues, such as liver tissues > PBMCU cancers and so on. Many studies have shown that the expression of IFNR in the liver tissues or PBMC. May be one of the hosts factors influencing the response to IFN therapy.So determining the distribution of the individual alpha/beta IFNR in the liver tissues and peripheral blood mononuclear cell(PBMC) is an important task. Our purpose was to study the immunohistochemical amount of alpha/beta IFNR in the liver tissues and PBMC and its clinical significance. At the same time we have studied the HBV genotype of chronic active hepatitis( CAH) and its significance.The first part of our study, we investigated 21 chronic hepatitis B patients' alpha/beta IFNR in liver tissue using immunohistogy. At the same time, the inflammation grade were also concerned. To our surprise, the severe inflammation grade in liver tissues have significantly higher positive units (F=13.077,P=0.000). The former study have show that severe inflammation grade in liver tissues have good response to interferon. So we speculate that the higher alpha/beta INFR may play a significant part.And then, we test 11 persons' alpha/beta IFNR in PBMC, including 5 normal persons and 6 patients with chronic hepatitis B. The equal t test shows that there is no significant difference between them. However study have shown that alpha/beta IFNR in PBMC in chronic hepatitis C patients was higher than normal persons and can predict the rate of response to IFN.By sequencing the whole genome or the S region of HBV DNA, eight genotypes: A-H can be described. Several reports mainly from countries with prevalence of HBV genotype B and C showed that clinical course and treatment of hepatitis B virus infection maybe influenced by the infecting HBV genotype. So the second part of our study aims to investigate the genotype of HBV and its clinical significance .Our study was to investigate the distribution of hepatitis B virus (HBV) genotypes in GuangDong area and its biological and clinical significance. Fifty-five patients with chronic active hepatitis (CAH) from GuangDong area were included. The fragments of surface gene of HBV amplified by PCR were analyzed by the method of restricted fragments length polymorphism (RFLP) to typing HBV genotype. The relationship of HBV genotype with clinical, serology and histology data was analyzed. Twenty-eight out of fifty five patients were infected with HBV strains of genotype B(51.0%),18 patients with genotype C(32.7%), 4 patients withgenotype D(7.3%), 4 patients with HBV strains which were classified as genotype B+C (7.3%), 1 patent (1.8%) could not be classified from HBV genotype A to G. There is no significant difference neither in clinical, histological, nor in sera HBV DNA loading between genotype B and C. But in those patients who were older than 30 years, HBV DNA loading and HBeAg level in serum were higher in genotype C than in genotype B (P<0.01, Fish' s exact test P=0.002). These results indicate that HBV genotype B and C are the major genotype in GuangDong area. Genotype C is associated with the longer duration of HBeAg and higher HBV DNA level when the age of patients was older than 30 years. This implies that patients infected with HBV genotype C may prone to progress into chronic liver disease.