Jackson S, Moldoveanu Z, Kirk K A, Julian B A, Patterson T F, Mullins A L, Jilling T, Mestecky J, Galla J H
Department of Microbiology, University of Alabama, Birmingham 35294.
Clin Exp Immunol. 1992 Aug;89(2):315-20. doi: 10.1111/j.1365-2249.1992.tb06952.x.
The possibility that patients with IgA nephropathy (IgAN) might have abnormal IgA immune responses to immunogens commonly encountered at mucosal surfaces, resulting in the formation of circulating immune complexes (CIC), was examined. Since it is generally held that such increased IgA responses are characterized by detectable aberrancies in handling of IgA-containing CIC, IgAN patients and controls were given a large volume of bovine milk (after dietary deprivation of bovine antigens) and immune complex levels were measured over a period of 12 h. An assay based on binding of CIC containing C3 to solid-phase anti-C3 and subsequent development with isotype-specific antibody revealed no differences in responses of patients and controls with respect to IgG- and IgM-containing CIC. Although IgAN patients tended to have higher levels of IgA-containing CIC, there were no differences in response patterns when IgA CIC levels after ingestion of the milk stimulus were related to baseline levels. Polymorphonuclear leucocytes (PMNC), which bear surface receptors for IgA, were isolated from some subjects at the same times as the samples for CIC levels and examined by two-colour immunofluorescence for the coincident presence of IgA and milk antigens. In contrast to the data obtained in the CIC assays, these experiments revealed the simultaneous presence of IgA and two of three milk proteins in PMNC of IgAN patients but not controls. Follow-up experiments designed to assess more quantitatively the coincidental presence of IgA and milk antigens indicated no significant differences between patients and controls. However, milk proteins seemed to be more commonly associated with IgA in PMNC of IgAN patients, suggesting the presence of non-complement-fixing IgA/antigen CIC after mucosal challenge of some IgAN patients.
研究了IgA肾病(IgAN)患者对黏膜表面常见免疫原可能存在异常IgA免疫反应,从而导致循环免疫复合物(CIC)形成的可能性。由于一般认为这种IgA反应增强的特征是在处理含IgA的CIC时可检测到异常,因此在给予IgAN患者和对照组大量牛奶(在饮食中去除牛抗原后)后,在12小时内测量免疫复合物水平。基于含C3的CIC与固相抗C3结合并随后用同型特异性抗体显色的检测方法显示,患者和对照组在含IgG和IgM的CIC反应方面没有差异。尽管IgAN患者含IgA的CIC水平往往较高,但摄入牛奶刺激后IgA CIC水平与基线水平相关时,反应模式没有差异。从一些受试者中分离出带有IgA表面受体的多形核白细胞(PMNC),与检测CIC水平的样本同时采集,并通过双色免疫荧光检测IgA和牛奶抗原的同时存在。与CIC检测获得的数据相反,这些实验显示IgAN患者而非对照组的PMNC中同时存在IgA和三种牛奶蛋白中的两种。旨在更定量评估IgA和牛奶抗原同时存在情况的后续实验表明,患者和对照组之间没有显著差异。然而,牛奶蛋白似乎更常与IgAN患者PMNC中的IgA相关联,这表明一些IgAN患者黏膜受到刺激后存在非补体结合性IgA/抗原CIC。