Deficient IgA1 immune response to nasal cholera toxin subunit B in primary IgA nephropathy
Deficient IgA1 immune response to nasal cholera toxin subunit B in primary IgA nephropathy
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DOI：
10.1038/ki.1996.396
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发表时间：
1996-09-01
影响因子：
19.6
通讯作者：
Bake, AWLV
中科院分区：
文献类型：
--
作者：
deFijter, JW;Eijgenraam, JW;Bake, AWLV
用新型蛋白抗原霍乱毒素B亚单位（CT B）经鼻和匙孔血蓝蛋白（KLH）皮下免疫12例伊加肾病（IgAN）患者和18例对照。采用ELISPOT法和ELISA法分别检测体液中抗体分泌细胞和抗体反应。方差分析显示，与对照组相比（P < 0.001），在IgAN患者的鼻洗液中没有CTB特异性IBA反应。IgAN患者外周血CTB特异性抗体分泌细胞数和血浆CTB特异性抗体数均明显低于正常对照组（P < 0.001和P < 0.005），且均局限于IgA 1亚类。骨髓抽吸物中CTB特异性IgA 1分泌细胞的比例与血浆中相应的比例显著相关，IgAN中的值显著低于对照组（P < 0.005）。这些结果支持人类存在“粘膜-骨髓轴”。但IgAN中未发现这种异常。在本研究中观察到的在初次粘膜免疫后对CTB的粘膜伊加免疫应答缺陷表明IgAN患者在鼻内攻击时具有缺陷的免疫应答。这些患者在建立有效的粘膜免疫之前可能依赖于粘膜部位更频繁和/或更长时间的抗原接触。重复接种抗原特异性细胞的次级类胚器官可能会导致继发性的相对高反应性IgAN后，通过胃肠外免疫再激活。
Twelve IgA nephropathy (IgAN) patients and 18 controls were immunized with novel protein antigens, cholera toxin subunit B (CTB) via the nasal route and keyhole limpet hemocyanin (KLH) subcutaneously. Antibody secreting cells and antibody response in body fluids were determined by ELISPOT assay and ELISA, respectively. Analysis of variance showed, in contrast to controls (P < 0.001), no CTB-specific IBA response in the nasal washes of patients with IgAN. Significantly lower numbers of CTB-specific antibody-secreting cells in peripheral blood (P < 0.001) and CTB-specific antibodies in plasma (P < 0.005) were found in IgAN, both restricted to the IgA1 subclass. The proportions of CTB-specific IgA1-secreting cells in bone marrow aspirates correlated significantly with the corresponding ratios in plasma, with significantly lower values (P < 0.005) in IgAN as compared to controls. These results support the existence of a 'mucosa-bone marrow axis' in humans. but no dysregulation of this asis was found in IgAN. The deficient mucosal IgA immune response to CTB observed in this study after primary mucosal immunization indicates that patients with IgAN have a defective immune response when challenged intranasally. These patients may depend on more frequent and/or prolonged antigen encounter at mucosal sites before efficient mucosal immunity Is established. Repeated seeding of antigen-specific cells to secondary lympoid organs could result secondarily in the relative hyperresponsiveness found in IgAN upon reactivation by parenteral immunization.