Renal Department and Nephrology Institute, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Renal and Metabolic Division, The George Institute for Global Health, University of NSW, Sydney, Australia; Department of Renal Medicine, Concord Repatriation General Hospital, Concord, Australia; The Concord Clinical School, University of Sydney, Sydney, Australia.
Ann Palliat Med. 2021 Sep;10(9):9453-9466. doi: 10.21037/apm-21-2065.
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.
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.
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).
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.
几项全基因组关联研究发现，人类白细胞抗原（HLA）Ⅱ类组织相容性抗原 DQβ1（HLA-DQB1）和 HLA Ⅱ类组织相容性抗原 DRβ1（HLA-DRB1）与免疫球蛋白 A 肾病（IgAN）有关。然而，很少有研究探讨 HLA-DQB1 和 HLA-DRB1 表达与 IgAN 的关系。这是第一项研究 HLA-DQB1 和 HLA-DRB1 表达与临床病理特征之间关系的研究。
本研究共纳入 113 例经肾活检证实的 IgAN 患者和 71 名健康对照者。采用实时定量逆转录聚合酶链反应（qRT-PCR）和流式细胞术检测外周血淋巴细胞中 HLA-DQB1 和 HLA-DRB1 的表达。采用酶联免疫吸附试验试剂盒检测血清半乳糖缺乏 IgA1（Gd-IgA1）水平。收集 IgAN 患者肾活检时的临床和组织病理学资料。采用 Pearson 或 Spearman 相关系数分析 HLA-DQB1 和 HLA-DRB1mRNA 和蛋白表达与 IgAN 临床病理特征的相关性。
与健康对照组相比，IgAN 患者 HLA-DQB1 和 HLA-DRB1 信使核糖核酸表达降低（P<0.01）。IgAN 患者 HLA-DQB1 和 HLA-DRB1 蛋白表达明显低于健康对照组（P<0.05）。HLA-DQB1 和 HLA-DRB1 蛋白表达与 24 小时尿蛋白排泄量呈正相关（P<0.05）。HLA-DRB1 蛋白表达与估算肾小球滤过率（P<0.05）呈负相关。新月体性 IgAN 患者 HLA-DRB1 蛋白表达高于无新月体形成患者（P<0.05）。
本研究发现 HLA-DQB1、HLA-DRB1 的表达与 IgAN 疾病的严重程度有关，异常的 HLA-DQB1 和 HLA-DRB1 表达可能加重 IgAN 的进展。我们打算收集进一步的随访数据，以探讨 HLA-DQB1 和 HLA-DRB1 表达对 IgAN 预后的影响。
