HLA-DQB1 and HLA-DRB1 expression is associated with disease severity in IgAN

Background: Several genome-wide association studies have found that HLA class II histocompatibility antigen, DQ beta1 (HLA-DQB1) and HLA class II histocompatibility antigen, DR beta1 (HLA-DRB1) were associated with immunoglobulin A nephropathy (IgAN). However, few studies have explored the association between HLA-DQB1 and HLA-DRB1 expression and IgAN. This is the first study to investigate the relationship between HLA-DQB1 and HLA-DRB1 expression and clinical pathological characteristics.

Methods: A total of 113 patients with biopsy-proven IgAN and 71 healthy control patients participated in this study. HLA-DQB1 and HLA-DRB1 expression in peripheral blood lymphocytes was measured by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and flow cytometry. Serum galactose-deficient IgA1 (Gd-IgA1) level was measured by an enzyme-linked immunosorbent assay kit. The clinical and histopathological data of patients with IgAN were collected at the time of renal biopsy. Pearson's or Spearman's correlation coefficients were used to analyze the correlation between the expression of HLA-DQB1 and HLA-DRB1 mRNA and protein and the clinical pathological features of IgAN.

Results: HLA-DQB1 and HLA-DRB1 messenger ribonucleic acid expression was decreased in IgAN patients compared to healthy control patients (P<0.01). HLA-DQB1 and HLA-DRB1 protein expression was significantly lower in IgAN patients than healthy control patients (P<0.05). HLA-DQB1 and HLA-DRB1 protein expression was positively correlated with 24-h urinary protein excretion (P<0.05). HLA-DRB1 protein expression was negatively correlated with renal function as measured by an estimated glomerular filtration rate (P<0.05). HLA-DRB1 protein expression was higher in patients with crescentic IgAN than patients without crescent formation (P<0.05).

Conclusions: Our study found the expression of HLA-DQB1, HLA-DRB1 were associated with the disease severity of IgAN and abnormal HLA-DQB1 and HLA-DRB1 expression may aggravate the progression of IgAN. We intend to gather further follow-up data to explore the effects of HLA-DQB1 and HLA-DRB1 expression on the prognosis of IgAN.