Jeruc J, Jurcić V, Vizjak A, Hvala A, Babic N, Kveder R, Praprotnik S, Ferluga D
Institute of Pathology, Faculty of Medicine, Ljubljana, Slovenia.
Wien Klin Wochenschr. 2000 Aug 25;112(15-16):702-6.
Glomerular lesions in lupus nephritis have been extensively studied in recent decades, but much less attention has been paid to the tubulo-interstitial compartment. The aim of this study was to contribute to the understanding of the pathogenesis of tubulo-interstitial lesions in lupus nephritis by analysing their incidence, character, and their associations. One hundred and ninety kidney biopsies of 190 patients fulfilling American Rheumatology Association (ARA) criteria of systemic lupus erythematosus (SLE) were examined by traditional light, immunofluorescence and electron microscopy. Interstitial inflammatory infiltration and tubulo-interstitial immune deposits concurred in 72 cases (37.9%). Their frequency was the highest in WHO class IV lupus glomerulonephritis. By multivariate analysis, the intensity of interstitial inflammatory infiltration correlated best with the percentage of renal corpuscules with extracapillary crescents and the extent of interstitial fibrosis. On immunohistochemical assessment, the inflammatory infiltrate was found to be composed of CD45RO positive T lymphocytes (191.3/mm2), CD68 positive macrophages (101.7/mm2) and CD45RA positive B lymphocytes (17.2/mm2). For all cell types the median value was higher in cases with extracapillary crescents, and did not correlate with presence and intensity of tubulo-interstitial immune deposits. Infiltration showed the tendency of periglomerular distribution, especially around glomeruli showing extracapillary proliferation and destruction of the capsular basal membrane. Rare S100 positive cells were only found in the interstitium. Tubulo-interstitial lesions estimated semiquantitatively correlated with the degree of proteinuria. Our findings suggest that tubulo-interstitial deposits do not play a major role in the pathogenesis of tubulo-interstitial lesions. The formation of interstitial cell infiltrates appears to be greatly influenced by the development of extracapillary crescents, perhaps by direct transmission of the severe inflammatory process to the adjacent interstitium. The composition of the infiltrate, including antigen presenting cells may signalize an additional involvement of cell-mediated immune mechanisms acting against so far hypothetical tubular epithelial neoantigens.
近几十年来，狼疮性肾炎的肾小球病变已得到广泛研究，但肾小管间质部分受到的关注要少得多。本研究旨在通过分析肾小管间质病变的发生率、特征及其相关性，来促进对狼疮性肾炎肾小管间质病变发病机制的理解。对190例符合美国风湿病学会（ARA）系统性红斑狼疮（SLE）标准的患者的190份肾活检标本进行了传统光学、免疫荧光和电子显微镜检查。72例（37.9%）出现间质炎症浸润和肾小管间质免疫沉积物。其发生率在世界卫生组织（WHO）IV级狼疮性肾小球肾炎中最高。多因素分析显示，间质炎症浸润强度与伴有毛细血管外新月体的肾小体百分比及间质纤维化程度相关性最佳。免疫组化评估发现，炎症浸润由CD45RO阳性T淋巴细胞（191.3/mm²）、CD68阳性巨噬细胞（101.7/mm²）和CD45RA阳性B淋巴细胞（17.2/mm²）组成。对于所有细胞类型，毛细血管外新月体病例的中位数更高，且与肾小管间质免疫沉积物的存在及强度无关。浸润显示出肾小球周围分布的趋势，尤其是在显示毛细血管外增殖和肾小囊基底膜破坏的肾小球周围。仅在间质中发现罕见的S100阳性细胞。半定量估计的肾小管间质病变与蛋白尿程度相关。我们的研究结果表明，肾小管间质沉积物在肾小管间质病变的发病机制中不起主要作用。间质细胞浸润的形成似乎受毛细血管外新月体发展的极大影响，可能是由于严重炎症过程直接蔓延至邻近间质。浸润成分，包括抗原呈递细胞，可能表明针对迄今假设的肾小管上皮新抗原的细胞介导免疫机制的额外参与。
