Correlation Between IgA Nephropathy And Expression Of HLA-DQB1、HLA-DRB1 MRNA And Associated Antigen

Objective: In recent years,the genome-wide association study(GWAS)suggests that alleles of HLA-DQB1 and HLA-DRB1 are closely related to the susceptibility of Ig A nephropathy(Ig AN),but the mechanism of action is still unclear.The deposition of galactose-deficient Ig A1(Gd-Ig A1)in the mesangial membrane is the key to the pathogenesis of Ig AN.The aim of this study was to understand the expression of HLA-DQB1,HLA-DRB1 m RNA and associated antigen between Ig AN and normal controls,and to analyze its correlation with Gd-Ig A1.Meanwhile to understand whether the indicators above are related to the clinical characteristics of the patient when combined their clinical data.Methods: 86 patients diagnosed with IgAN via renal biopsy in the Department of Nephrology of Sichuan Provincial People’s Hospital from May 2018 to January 2019 were enrolled.Peripheral blood samples of all patients were collected at the same time.32 normal controls with age and gender matched were included.The expression of HLA-DQB1 and HLA-DRB1 m RNA in peripheral blood lymphocytes were detected by q RT-PCR(Quantitative Real-time PCR).The expression of HLA-DQ and HLA-DR antigen in peripheral blood nucleated cells was detected by flow cytometry.Serum Gd-Ig A1 levels were measured by ELISA.The differences of the indicators above between the Ig AN group and the control group were compared,and the correlation between Gd-Ig A1 and expression of HLA-DQB1,HLA-DRB1 m RNA and associated antigen was analyzed.Patients’ clinical data were collected at the time of renal biopsy,and the correlation between the expression of HLA-DQB1,HLA-DRB1 m RNA and associated antigen and the clinical features of Ig AN patients was analyzed.Results: 1.The BMI,blood pressure,level of serum creatinine and blood uric acid in the Ig AN group were higher than those in the control group(P<0.05),while the glomerular filtration rate and serum albumin were lower than those in the control group(P<0.05).2.The relative expression of HLA-DQB1 and HLA-DQB1 m RNA in peripheral blood lymphocytes of Ig AN group was lower than that of the control group(P<0.05).3.The antigen expression of HLA-DQ on T cells,NK cells and monocytes of IgAN group was higher than that of the control group(P<0.05).The expression level of HLA-DR antigen on T cells in Ig AN group showed a tendency of increase than that of the control group,but no presence of statistical difference(P = 0.08).4.The serum Gd-Ig A1 level in the Ig AN group was significantly higher than that in the control group(P<0.01).5.There was no correlation between HLA-DQB1,HLA-DRB1 m RNA expression and HLA-DR antigen expression level and serum Gd-Ig A1 level in Ig AN patients,but the expression of HLA-DQ antigen on T cells showed a tendency of positive correlation with serum Gd-Ig A1(P=0.19,r=0.31).6.The expression of HLA-DQ antigen on peripheral blood NK cells of Ig AN patients was positively correlated with proteinuria and serum creatinine(r=0.58,r=0.47).The expression of HLA-DQ antigen on peripheral blood B cells was negative correlated with C3 complement(r=-0.46).The expression of HLA-DR antigen on peripheral blood NK cells was positively correlated with proteinuria in patients with Ig AN(r=0.48).The expression of HLA-DR antigen on peripheral blood nucleated cells,lymphocytes,B cells was positively correlated with uric acid,repectively(r=0.46,r=0.53,r=0.52).7.The serum Gd-Ig A1 level in patients with Ig AN was positively correlated with diastolic blood pressure,BMI and serum immunoglobulin A,repectively(r=0.22,r=0.25,r=0.42).8.The m RNA expression of HLA-DQB1 、 HLA-DRB1 in peripheral blood lymphocytes were not associated with various clinical indicators in Ig AN patients.Conclusion:1.The m RNA expression of HLA-DQB1 and HLA-DRB1 decreased in peripheral blood lymphocytes of Ig AN patients.2.The antigens of HLA-DQ and HLA-DR increased on peripheral blood T cells of Ig AN patients,which suggested that HLA-DQ and HLA-DR may participate in the pathogenesis of Ig AN through T cells.3.The serum Gd-Ig A1 level in Ig AN patients was significantly increased,which showed a tendency of positive correlation with the expression of HLA-DQ antigen on T cells,which suggested that antigen of HLA-DQ may potentially has the relationship with the production of Gd-Ig A1,but the sample size needs to be expanded for further analysis.