Expression Of HLA-G Molecule In Crescentic Glomerulonephritis And Its Clinical Significance

Backgroud and objective: Crescentic glomerulonephritis(CGN) is the most aggressive form of glomerulonephritis. It’s a fatal disease with poor prognosis, rapidly leading to end-stage renal disease or to death. It can be resulted from numerous causes. Prognostic factors included oligo-anuria, the degree of kidney failure,hemodialysis dependence, and the percentage of crescentic glomeruli on biopsy. The pathogenesis of CGN is not clear at present, and many studies have shown that it’s inflammation and immune disorders. In recent years, human leukocyte antigen-G(HLA-G) was found to be an important immune-regulatory molecular. Its function is typically receptor-mediated, and involves interactions with a wide range of immune cells, in both the innate and adaptive immunity. It played an important role in the development of neoplasm, pregnancy, transplantation and so forth. The immunosuppressive effect of HLA-G makes cells escaping from the body’s immune surveillance and immune tolerance, appearing a large number of proliferated cells. Crescentic Glomerulonephritis is a kind of hyperplastic diseases. Our hypothesis is that HLA- G would expressed in a high level in the patients with CGN, which leads to escape immune surveillance and strengthen immune tolerance, and result in cell proliferation and formation of crescent. Our purpose of this study is to assay the concentrations of serum soluble HLA-G(s HLA-G)in patients with CGN and to analyze its clinical significance.Methods : 1. Total 48 patients with CGN from 2009 to 2014 were involved in this study. The clinical data were collected, include demographic characteristics, laboratory parameters, pathological examinations,prognostic information and immunosuppressive therapy. Analyze if oliguria or anuria, serum creatinine levels, the crescent formation ratio and therapy would affect the prognosis of patients.2. We collected 22 patients with CGN from 2009 to 2014 and 15 patients with MCD in the same period,30 healthy adults in control group. Detected the serum levels of s HLA-G by ELISA. Analyzed the relationship between the clinical or pathological features and s HLA-G. Investigated the value of the HLA-G in crescentic glomerulonephritis.Results:1.The prognosis of patients with crescentic nephritis. Although the patients we included had only one case of death, but the 3-years kidney survival rate was only 38%. This study showed that serum creatinine levels in ESRD group was higher than the proportion of non-ESRD group. Kaplan Meier survival curves showed that oliguria or anuria( P=0.0438) and serum creatinine>5mg/d(P=0.000587)would affect the prognosis, and the age, sex and crescent formation ratio had no significant effect on the prognosis. Cox regression analysis showed higher serum creatinine associated with the patients with a poor prognosis(HR=4.04,95%Cl:1.548-10.544, P=0.004).Univariate analysis showed that patients with hemodialysis at admission associated with the patients with a poor prognosis(P=0.0002).2.The serum level of s HLA-G. The serum level of s HLA-G in CGN was significantly higher than in healthy control(2198.81 ± 1924.17pg/ml vs.1311.86 ± 448.84pg/ml, P=0.0408), while higher than that MCD,(2198.81 ± 1924.17 pg/ml vs. 1181.33 ± 320.10 pg/ml, P=0.023). We used mean +2×standard deviation as a reference(2209.54pg/ml) and divided 22 cases into two groups. The results showed that the serum creatinine levels and the proportions within six months into ESRD was different between two groups,but no statistical significance(P > 0.05).The crescent formation ratio between two groups had no statistical significance. Kaplan Meier survival analysis showed elevated levels of HLA-G in patients with poor prognosis is obvious, but the difference was not statistical significance(P=0.171).Conclusions: 1.We have shown that the oligo-anuria, high serum creatinine level(>5mg/dl) at admission are closely related to ESRD progression. Our data showed high serum creatinine level(>5mg/dl) at admission was an independent risk factor for the development to be ESRD. And the patient who was hemodialysis at admission had a poor renal function and severe condition.2.s HLA-G was significantly elevated in the serum of patients with CGN, and the level of s HLA-G had relationship with the prognosis of the patients with CGN. s HLA-G may be used as a new biomarker in CGN with clinical value in the early diagnosis and prognosis.