Coppo R, Amore A, Gianoglio B, Porcellini M G, Peruzzi L, Gusmano R, Giani M, Sereni F, Gianviti A, Rizzoni G
Nephrology Unit of Regina Margherita Children's Hospital, Torino, Italy.
Clin Nephrol. 1995 Jan;43(1):1-13.
This multicenter study investigated the characteristics of circulating IgA molecules in 77 children: 42 had primary IgA nephropathy (IgAN), 20 were non-IgA glomerulonephritides (CGN) and 15 had urological problems (U). Fifteen assays were employed including the detection of macromolecular IgA [IgA immune complexes (IgAIC) by the conglutinin (K) assay, heavy molecular weight IgA in 2.5% polyethylene glycol (PEG), mixed IgA/IgGIC (Jacalin assay), IgA-Fibronectin (IgA-F) aggregates]IgA antibodies to alimentary antigens (gliadin, glycgli, glutein, ovalbumin, bovine serum albumin) and IgA binding to mesangial antigens (fibronectin, laminin, type IV collagen) or polycations (poly-L-lysine). Total IgA and IgA reacting with jacalin, supposed to bear an altered galactosylation, were measured as well. Mean levels of each kind of macromolecular IgA were significantly increased in children with IgAN in comparison to U disease (K-IgAIC p < 0.05, PEG-IgAIC p < 0.01, IgA/IgGIC p < 0.004, IgA-F aggregates p < 0.0003). However, IgA-F were the only macromolecular IgA significantly higher in IgAN than in CGN (p < 0.0005). IgA-F aggregates did not correlate with any urinary sign of activity, while K-IgAIC data were significantly related with microscopic hematuria (p < 0.05) and past history of gross hematuria (p < 0.02). Children with IgAN had mean levels of IgA reacting with the lectinic fractions of gliadin significantly higher than CGN (p < 0.01) and U groups (p < 0.003). IgAN displayed an enhanced production of IgA reacting with mesangial matrix components vs CGN (p < 0.03) and U (p < 0.0003) groups and showed altered interactions with positively charged molecules (poly-L-Lysine, p < 0.01) and carbohydrate residues (jacalin p < 0.05). In IgAN there is an increased circulation of altered IgA favouring the formation of macromolecular IgA, including true IgAIC or IgA aggregated by carbohydrate interactions. The affinity for the mesangial matrix glycoproteins and for the mesangial area electrical charge might further enhance the trapping and deposition of the immune material containing IgA. IgA-F aggregates seem to be a marker of this event, while complement binding molecules in IgAIC correspond to the hematuric manifestation of the nephritogenic process.
这项多中心研究调查了77名儿童循环免疫球蛋白A（IgA）分子的特征：42名患有原发性IgA肾病（IgAN），20名患有非IgA肾小球肾炎（CGN），15名有泌尿系统问题（U）。采用了15种检测方法，包括检测大分子IgA[通过胶固素（K）检测法检测IgA免疫复合物（IgAIC）、在2.5%聚乙二醇（PEG）中检测重分子量IgA、混合IgA/IgGIC（红豆凝集素检测法）、IgA-纤连蛋白（IgA-F）聚集体]、针对食物抗原（麦醇溶蛋白、糖麦醇溶蛋白、麦谷蛋白、卵清蛋白、牛血清白蛋白）的IgA抗体以及IgA与系膜抗原（纤连蛋白、层粘连蛋白、IV型胶原）或聚阳离子（聚-L-赖氨酸）的结合。还测量了总IgA以及与红豆凝集素反应的IgA（推测其半乳糖基化发生改变）。与泌尿系统疾病（U）相比，IgAN患儿中各类大分子IgA的平均水平显著升高（K-IgAIC p<0.05，PEG-IgAIC p<0.01，IgA/IgGIC p<0.004，IgA-F聚集体p<0.0003）。然而，IgA-F是唯一在IgAN中显著高于CGN的大分子IgA（p<0.0005）。IgA-F聚集体与任何尿液活动迹象均无相关性，而K-IgAIC数据与镜下血尿显著相关（p<0.05）以及肉眼血尿既往史显著相关（p<0.02）。IgAN患儿中与麦醇溶蛋白凝集素部分反应的IgA平均水平显著高于CGN组（p<0.01）和U组（p<0.003）。与CGN组（p<0.03）和U组（p<0.0003）相比，IgAN显示出与系膜基质成分反应的IgA产生增加，并表现出与带正电荷分子（聚-L-赖氨酸，p<0.01）和碳水化合物残基（红豆凝集素，p<0.05）的相互作用改变。在IgAN中，发生改变的IgA循环增加，有利于大分子IgA的形成，包括真正的IgAIC或通过碳水化合物相互作用聚集的IgA。对系膜基质糖蛋白和系膜区电荷的亲和力可能会进一步增强含IgA免疫物质的捕获和沉积。IgA-F聚集体似乎是这一事件的标志物，而IgAIC中的补体结合分子则对应于致肾炎过程的血尿表现。
