Markovic-Lipkovski J, Müller C A, Risler T, Bohle A, Müller G A
Department 3, Medical University Clinic, Eberhard-Karls-University, Tübingen, FRG.
Nephron. 1991;59(2):286-93. doi: 10.1159/000186566.
Immunophenotyping of infiltrating glomerular and interstitial mononuclear leukocytes performed in renal tissues of 15 patients with focal segmental glomerulosclerosis (FSGS) was compared to 15 normal kidneys in order to investigate a possible role for cell-mediated immunity (CMI) in FSGS. In addition, distribution of HLA class II (-DQ, -DR, -DP and -DY) antigens and of the intercellular adhesion molecule 1 (ICAM-1) as well as the expression of well-defined renal antigens along the human nephron was analyzed. In comparison to normal kidneys, a reduction in HLA class II antigens of ICAM-1 and of renal antigens defined by the monoclonal antibodies TN8-TN10 was observed in sclerotic glomeruli. Furthermore, an increased number of T lymphocytes was found in glomeruli of FSGS with slight predominance of the CD8+ subset. Interstitial inflammation was present in all FSGS cases except 1 with T lymphocytes and monocytes/macrophages constituting the predominant infiltrating cell types. In contrast to the glomerular T cells, the number of interstitial CD4+ cells was greater than the number of CD8+ cells in almost all cases. As a sign of activation, most interstitial inflammatory cells carried HLA class II antigens and some of them also expressed ICAM-1. Proximal tubular epithelial cells often presented an abnormal expression of HLA-DQ and HLA-DP antigens associated with aberrant expression of ICAM-1 and TN8. The number of interstitial mononuclear leukocytes was correlated to serum creatinine levels at the time of renal biopsy. The present results provide further support for the involvement of CMI in the pathogenesis of FSGS.
对15例局灶节段性肾小球硬化(FSGS)患者肾组织中浸润的肾小球和间质单核白细胞进行免疫表型分析,并与15个正常肾脏进行比较,以研究细胞介导免疫(CMI)在FSGS中可能发挥的作用。此外,还分析了HLA II类(-DQ、-DR、-DP和-DY)抗原、细胞间黏附分子1(ICAM-1)的分布以及沿人类肾单位的明确肾抗原的表达。与正常肾脏相比,在硬化性肾小球中观察到ICAM-1的HLA II类抗原和由单克隆抗体TN8-TN10定义的肾抗原减少。此外,在FSGS的肾小球中发现T淋巴细胞数量增加,CD8+亚群略有优势。除1例FSGS病例外,所有病例均存在间质炎症,T淋巴细胞和单核细胞/巨噬细胞构成主要浸润细胞类型。与肾小球T细胞不同,几乎在所有病例中间质CD4+细胞的数量都大于CD8+细胞的数量。作为激活的标志,大多数间质炎症细胞携带HLA II类抗原,其中一些还表达ICAM-1。近端肾小管上皮细胞常出现HLA-DQ和HLA-DP抗原的异常表达,并伴有ICAM-1和TN8的异常表达。间质单核白细胞的数量与肾活检时的血清肌酐水平相关。目前的结果为CMI参与FSGS的发病机制提供了进一步的支持。