Castiglione A, Bucci A, Fellin G, d'Amico G, Atkins R C
Divisione di Nefrologia Ente Ospedaliero San Carlo Borromeo, Milano, Italia.
Nephron. 1988;50(1):14-23. doi: 10.1159/000185110.
In order to evaluate the contribution of cellular immune mechanisms in the pathogenesis of immune complex-mediated glomerulonephritis, renal biopsies from 18 patients with lupus glomerulonephritis and 26 with cryoglobulinaemic glomerulonephritis were studied. Leucocyte profiles including T cell subsets and 'activated' macrophages within both glomeruli and interstitium were determined, using a panel of monoclonal antibodies as markers, and a sensitive 4-layer peroxidase technique to localize these within tissues. The infiltrating leucocytes were correlated with clinical, histological and immunological parameters of disease activity. Normal glomeruli contained few leucocytes though normal interstitium did (145 +/- 30 mm2), made up predominantly of T lymphocytes and macrophages. There was a significant increase in intraglomerular leucocytes in both systemic lupus erythematosus 4-fold, and essential mixed cryoglobulinaemia 7-fold, as compared to normal. These leucocytes consisted mainly of macrophages, and particularly in cryoglobulinaemia of 'activated' macrophages as demonstrated by their surface expression of the procoagulant tissue factor recognized by the A13 monoclonal antibody. In cryoglobulinaemic glomerulonephritis (GN) there was also a significant increase in T lymphocytes due to a predominance of suppressor-cytotoxic cells (OKT8+). There was a significant increase in interstitial leucocytes in both diseases, lymphocytes (mainly OKT8+ve), and macrophages (mainly 'activated' A13+ve). There were significant positive correlations between disease activity and interstitial leucocyte infiltration including, in lupus nephritis, degree of proteinuria and total leucocytes, hypocomplementaemia and T lymphocytes, increased numbers of monocytes and lymphocytes with a higher histological index of activity, and in cryoglobulinaemic GN of T lymphocytes and proliferative lesions, and T lymphocytes and C1q deposition. This study has demonstrated the importance of the interstitium in the pathogenesis of both diseases, delineated the presence of both T lymphocytes and activated monocytes which make cell-mediated immune mechanisms feasible, and linked the presence of immune mediators to disease activity.
为了评估细胞免疫机制在免疫复合物介导的肾小球肾炎发病机制中的作用，我们研究了18例狼疮性肾小球肾炎患者和26例冷球蛋白血症性肾小球肾炎患者的肾活检组织。使用一组单克隆抗体作为标志物，并采用敏感的四层过氧化物酶技术在组织中定位，确定了肾小球和间质内的白细胞谱，包括T细胞亚群和“活化”巨噬细胞。将浸润的白细胞与疾病活动的临床、组织学和免疫学参数进行关联分析。正常肾小球内白细胞较少，而正常间质中则有（145±30个/mm²），主要由T淋巴细胞和巨噬细胞组成。与正常情况相比，系统性红斑狼疮患者肾小球内白细胞增加了4倍，原发性混合性冷球蛋白血症患者增加了7倍。这些白细胞主要由巨噬细胞组成，特别是在冷球蛋白血症中为“活化”巨噬细胞，这通过其表面表达A13单克隆抗体识别的促凝组织因子得以证明。在冷球蛋白血症性肾小球肾炎（GN）中，由于抑制性细胞毒性细胞（OKT8 +）占优势，T淋巴细胞也显著增加。两种疾病的间质白细胞均显著增加，包括淋巴细胞（主要是OKT8 +阳性）和巨噬细胞（主要是“活化”A13 +阳性）。疾病活动与间质白细胞浸润之间存在显著正相关，包括在狼疮性肾炎中，蛋白尿程度和总白细胞数、低补体血症和T淋巴细胞、单核细胞和淋巴细胞数量增加与较高的组织学活动指数，以及在冷球蛋白血症性GN中T淋巴细胞与增殖性病变、T淋巴细胞与C1q沉积。本研究证明了间质在两种疾病发病机制中的重要性，确定了T淋巴细胞和活化单核细胞的存在，这使得细胞介导的免疫机制成为可能，并将免疫介质的存在与疾病活动联系起来。
