HLA-DQB1 and HLA-DRB1 expression is associated with disease severity in IgAN.
HLA-DQB1 and HLA-DRB1 expression is associated with disease severity in IgAN.
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DOI：
10.21037/apm-21-2065
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发表时间：
2021-09
影响因子：
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通讯作者：
Xueyu Zhan;Fei Deng;A. Wang;Qin Chen;Yongjing Du;Qiuxia Wang;X. Zhong;Ping Zhang;Wen Wang;Shasha Chen;Guisen Li;Li Wang
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文献类型：
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作者：
Xueyu Zhan;Fei Deng;A. Wang;Qin Chen;Yongjing Du;Qiuxia Wang;X. Zhong;Ping Zhang;Wen Wang;Shasha Chen;Guisen Li;Li Wang
几项全基因组关联研究发现，HLA II类组织相容性抗原DQ β 1（HLA-DQB 1）和HLA II类组织相容性抗原DR β 1（HLA-DRB 1）与免疫球蛋白A肾病（IgAN）相关。然而，很少有研究探讨HLA-DQB 1和HLA-DRB 1表达与IgAN之间的关系。本研究首次探讨了HLA-DQB 1和HLA-DRB 1的表达与临床病理特征的关系。方法113例经活检证实的IgAN患者和71例健康对照者参加了这项研究。采用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-DQB 1和HLA-DRB 1的表达。采用酶联免疫吸附法测定血清半乳糖缺陷型IgA 1（Gd-IgA 1）水平。在肾活检时收集IgAN患者的临床和组织病理学资料。采用Pearson相关系数或斯皮尔曼相关系数分析HLA-DQB 1和HLA-DRB 1 mRNA和蛋白表达与IgA肾病临床病理特征的相关性。结果IgAN患者HLA-DQB 1和HLA-DRB 1 mRNA表达水平较健康对照组明显降低（P<0.01）。IgA肾病患者HLA-DQB 1和HLA-DRB 1蛋白表达明显低于健康对照组（P<0.05）。HLA-DQB 1和HLA-DRB 1蛋白表达与24 h尿蛋白定量呈正相关（P<0.05）。HLA-DRB 1蛋白表达与肾小球滤过率呈负相关（P<0.05）。伴新月体形成的IgA肾病患者HLA-DRB 1蛋白表达明显高于不伴新月体形成的IgA肾病患者（P<0.05）。结论HLA-DQB 1、HLA-DRB 1的表达与IgA肾病的病情严重程度相关，HLA-DQB 1、HLA-DRB 1的异常表达可能加重IgA肾病的病情进展。本研究拟进一步收集随访资料，探讨HLA-DQB 1和HLA-DRB 1表达对IgA肾病预后的影响。
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.