Purpose. It was reported that gut-kidney axis may play an important role in IgA nephropathy (IgAN). Previous five GWASs of different populations for IgAN have discovered several genes related to intestinal immunity, including DEFA gene. However, the roles of the encoded proteins of DEFA5/6 which were called intestinal antimicrobial peptides HD5 and HD6 were not clear in kidney disease, such as IgAN. The purpose of this study was to clarify the association of HD5 and HD6 with IgAN. Methods. We measured HD5 and HD6 in serum, urine, and kidney of IgAN patients and normal controls by ELISA, Western blot, and immunofluorescence. The association of HD5 or HD6 levels with clinical and pathologic phenotypes was analyzed. Results. Serum levels of HD5 and HD6 were significantly higher in IgAN patients than those in normal controls. Baseline serum HD5 levels were significantly associated with eGFR () and tubular atrophy/interstitial fibrosis () by stepwise multivariate regression analysis. Compared to the patients with serum HD5 below the median level, patients with elevated serum HD5 above the median level had a significantly worse renal outcome (log-rank test, ) by Kaplan-Meier analysis. A Cox regression model showed that serum HD5 was an independent prognostic factor (, ) after adjusting for the well-known predictors of outcome in IgAN patients. In renal biopsies of IgAN patients, HD5 was significantly expressed in the damaged proximal tubules, while no immunoreactive HD6 was found. Interestingly, the serum HD6 level of IgAN patients was significantly associated with gender. Conclusions. In IgAN patients, an elevated serum HD5 level at the time of renal biopsy was associated with poor renal outcomes. HD5 rather than HD6 was probably associated with renal function of IgAN patients.

中文翻译：

---

IgA肾病中与肾功能相关的肠道抗菌肽HD5表达上调。

目的。据报道，肠-肾轴可能在 IgA 肾病 (IgAN) 中起重要作用。之前针对 IgAN 不同人群的五个 GWAS 已经发现了几个与肠道免疫相关的基因，包括DEFA基因。然而，被称为肠道抗菌肽 HD5 和 HD6的DEFA5 / 6编码蛋白在 IgAN 等肾脏疾病中的作用尚不清楚。本研究的目的是阐明 HD5 和 HD6 与 IgAN 的关联。方法。我们通过 ELISA、蛋白质印迹和免疫荧光检测了 IgAN 患者和正常对照的血清、尿液和肾脏中的 HD5 和 HD6。分析了 HD5 或 HD6 水平与临床和病理表型的关联。结果。IgAN 患者的血清 HD5 和 HD6 水平显着高于正常对照组。基线血清 HD5 水平与 eGFR 显着相关（)和肾小管萎缩/间质纤维化 ()通过逐步多元回归分析。与血清 HD5 低于中值水平的患者相比，血清 HD5 升高高于中值水平的患者的肾脏结局显着更差（时序检验，)通过 Kaplan-Meier 分析。Cox回归模型显示血清HD5是独立的预后因素（, )在调整了众所周知的 IgAN 患者预后预测因子之后。在 IgAN 患者的肾活检中，HD5 在受损的近端小管中显着表达，而未发现免疫反应性 HD6。有趣的是，IgAN 患者的血清 HD6 水平与性别显着相关。结论。在 IgAN 患者中，肾活检时血清 HD5 水平升高与肾脏预后不良有关。HD5 而不是 HD6 可能与 IgAN 患者的肾功能有关。