Tanaka Keiko, Sugiyama Hitoshi, Morinaga Hiroshi, Kitagawa Masashi, Kano Yuzuki, Onishi Yasuhiro, Mise Koki, Tanabe Katsuyuki, Uchida Haruhito A, Wada Jun
Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
Department of Medicine, Kawasaki Medical School General Medical Center and Department of Medical Care Work, Kawasaki College of Allied Health Professions, Okayama 700-8505, Japan.
J Clin Med. 2023 Mar 3;12(5):2023. doi: 10.3390/jcm12052023.
IgA nephropathy (IgAN) is a major cause of chronic glomerulonephritis worldwide. T cell dysregulation has been reported to contribute to the pathogenesis of IgAN. Methods We measured a broad range of Th1, Th2 and Th17 cytokines in the serum of IgAN patients. We searched for significant cytokines, which were associated with clinical parameters and histological scores in IgAN patients.
Among 15 cytokines, the levels of soluble CD40L (sCD40L) and IL-31 were higher in IgAN patients and were significantly associated with a higher estimated glomerular filtration rate (eGFR), a lower urinary protein to creatinine ratio (UPCR), and milder tubulointerstitial lesions (i.e., the early phase of IgAN). Multivariate analysis revealed that serum sCD40L was an independent determinant of a lower UPCR after adjustment for age, eGFR, and mean blood pressure (MBP). CD40, a receptor of sCD40L, has been reported to be upregulated on mesangial cells in IgAN. The sCD40L/CD40 interaction may directly induce inflammation in mesangial areas and may therefore be involved in the development of IgAN.
The present study demonstrated the significance of serum sCD40L and IL-31 in the early phase of IgAN. Serum sCD40L may be a marker of the beginning of inflammation in IgAN.
IgA肾病（IgAN）是全球慢性肾小球肾炎的主要病因。据报道，T细胞失调参与了IgAN的发病机制。方法：我们检测了IgAN患者血清中多种Th1、Th2和Th17细胞因子。我们寻找与IgAN患者临床参数和组织学评分相关的显著细胞因子。
在15种细胞因子中，IgAN患者血清中可溶性CD40L（sCD40L）和IL-31水平较高，且与较高的估计肾小球滤过率（eGFR）、较低的尿蛋白肌酐比值（UPCR）以及较轻的肾小管间质病变（即IgAN早期）显著相关。多变量分析显示，在调整年龄、eGFR和平均血压（MBP）后，血清sCD40L是UPCR降低的独立决定因素。sCD40L的受体CD40在IgAN的系膜细胞上已被报道上调。sCD40L/CD40相互作用可能直接诱导系膜区炎症，因此可能参与IgAN的发展。
本研究证明了血清sCD40L和IL-31在IgAN早期的重要性。血清sCD40L可能是IgAN炎症开始的标志物。
