Ectopic germinal center and megalin defect in primary Sjogren syndrome with renal Fanconi syndrome.
Ectopic germinal center and megalin defect in primary Sjogren syndrome with renal Fanconi syndrome.
复制标题
DOI：
10.1186/s13075-017-1317-x
复制
发表时间：
2017-06-02
影响因子：
4.9
通讯作者：
Chen L
中科院分区：
文献类型：
--
作者：
Wang J;Wen Y;Zhou M;Shi X;Jiang L;Li M;Yu Y;Li X;Li X;Zhang W;Lundquist AL;Chen L
本研究报告了12例原发性干燥综合征（pSS）患者的临床和病理特征，并探讨了异位生发中心形成与megalin/cubilin表达下降的可能关系。回顾临床及病理资料。免疫组化法检测megalin、cubilin、CD 21、IL-17的表达。患者出现不同程度的近端肾小管病变和估计肾小球滤过率（eGFR）降低。肾活检显示肾小管间质性肾炎，肾小管上皮细胞变性，肾小管萎缩，间质炎症和局灶性纤维化。免疫组化显示megalin和cubilin，两个重要的多配体蛋白受体的近端肾小管上皮细胞刷状缘的表达减少。Th 17亚型效应T细胞分泌的IL-17在肾近曲小管中弥漫性表达，IL-17与megalin表达呈负相关。此外，异位生发中心的特点是CD 21+滤泡树突状细胞存在于肾间质。在eGFR降低的患者中，糖皮质激素治疗4周导致75%的患者eGFR改善。本文报告12例以Fanconi综合征为特征的pSS。megalin和cubilin表达的减少可能导致近端肾小管重吸收缺陷，可能继发于Th 17浸润和异位生发中心的形成。
This study reports the clinical and pathological features of 12 cases of primary Sjogren syndrome (pSS) with renal involvement presenting with proximal tubular dysfunction in a single center, and investigates the possible correlation of ectopic germinal center formation and megalin/cubilin down-expression. Clinical and pathological records were reviewed. Immunohistochemistry was carried out to detect megalin, cubilin, CD21 and IL-17 expression. Patients presented with different degrees of proximal renal tubule lesion and decreased estimated glomerular filtration rate (eGFR). Renal biopsy revealed tubulointerstitial nephritis, with tubular epithelial cell degeneration, tubular atrophy, interstitial inflammation and focal fibrosis. Immunohistochemistry revealed decreased expression of megalin and cubilin, two important multiligand protein receptors on the brush border of proximal tubular epithelial cells. IL-17 secreted by Th17 subtype effector T cells was diffusely detected in the renal proximal tubule, with a negative correlation of IL-17 and megalin expression. In addition, ectopic germinal centers characterized by CD21+ follicular dendritic cells were present in the renal interstitium. In patients with a decreased eGFR, treatment with 4 weeks of glucocorticoid therapy resulted in an improved eGFR in 75% of patients. We report 12 cases of pSS characterized by Fanconi syndrome. The decreased megalin and cubilin expression may contribute to the proximal tubular reabsorption defect, possibly secondary to Th17 infiltration and formation of ectopic germinal centers.