Roberts J L, Levy M, Chioros P G, Bartlow B G, Forristal J, West C D, Habib R, Lewis E J
J Immunol. 1981 Sep;127(3):1131-7.
A non-IgG C3 activating factor (C3AF) isolated from the serum and plasma of a patient with membranoproliferative glomerulonephritis with subendothelial and subepithelial deposits (type III) was studied to define its molecular structure, functional characteristics, and presence in renal biopsies. Alternative complement pathway (ACP) activation of C3 was comparable to that of zymosan, but significantly less than that of IgG C3 nephritic factor (C3NeF). Functionally active isolate contained beta 1H globulin (beta 1H) and the C3AF protein, which had a gamma-electrophoretic migration. beta 1H present in the isolate exhibited an altered gamma-beta electrophoretic mobility. The function of this complex is heat labile. Time/temperature studies demonstrated that inactivated preparations of this isolate show a return to the normal beta migration of beta 1H followed by the development of an alpha 2 electrophoretic migration of the previously gamma-migrating material of functionally active isolate. Normal human serums contain an alpha 2 protein that shows complete antigenic identity with the gamma protein of C3AF, but this alpha 2 protein lacks C3 activating function. On polyacrylamide gel electrophoresis, the C3AF isolate contains a high m.w. protein of 500,000 to 590,000 that is composed of 2 major subunits. Carbohydrate is not demonstrable, and the protein is antigenically distinct from plasma fibronectin. Immunofluorescence studies of renal biopsies of patients with types I and III MPGN revealed the presence of C3AF antigen in granular deposits in 10 of 16 cases. The presence of this antigen in glomerular deposits was associated with C3 and beta 1H, but was independent of Ig. These studies suggest that the mechanism of ACP activation by C3AF results from interference with beta 1H function. The presence of this material in renal biopsies from some MPGN patients further suggests a pathogenetic role in mediating glomerular pathology.
从一名患有伴有内皮下和上皮下沉积物的膜增生性肾小球肾炎（III型）患者的血清和血浆中分离出一种非IgG C3激活因子（C3AF），对其分子结构、功能特性及在肾活检组织中的存在情况进行了研究。C3的替代补体途径（ACP）激活与酵母聚糖相当，但明显低于IgG C3肾炎因子（C3NeF）。具有功能活性的分离物含有β1H球蛋白（β1H）和C3AF蛋白，该蛋白具有γ电泳迁移率。分离物中存在的β1H表现出改变的γ-β电泳迁移率。这种复合物的功能对热不稳定。时间/温度研究表明，该分离物的灭活制剂显示β1H恢复到正常的β迁移，随后先前具有功能活性的分离物中γ迁移物质出现α2电泳迁移。正常人血清含有一种α2蛋白，其与C3AF的γ蛋白具有完全抗原同一性，但这种α2蛋白缺乏C3激活功能。在聚丙烯酰胺凝胶电泳中，C3AF分离物含有一种分子量为500,000至590,000的高分子量蛋白，由2个主要亚基组成。未检测到碳水化合物，且该蛋白在抗原性上与血浆纤连蛋白不同。对I型和III型MPGN患者肾活检组织的免疫荧光研究显示，16例中有10例在颗粒沉积物中存在C3AF抗原。肾小球沉积物中该抗原的存在与C3和β1H相关，但与Ig无关。这些研究表明，C3AF激活ACP的机制是由于对β1H功能的干扰。一些MPGN患者肾活检组织中存在这种物质，进一步提示其在介导肾小球病理过程中具有致病作用。
