糖基化异常IgA1自身聚合或与IgG形成的大分子可能与IgA肾病病理表型相关

目的 IgA肾病是最常见的原发性肾小球疾病之一,其临床病理表型多种多样.血清中糖基化异常的IgA1及其与其他免疫球蛋白所形成的大分子复合物可能是本病重要的发病原因.本文探讨IgA1大分子复合物的组成和结构特征,及其与IgA肾病不同病理表型之间的关系.方法 制备偶联有去唾液酸IgA1（DesIgA1）和去唾液酸去半乳糖IgA1（DesDeGalIgA1）的琼脂糖亲和层析柱（DesIgA1/Sepharose,DesDeGalIgA1/Sepharose）.取10名轻度系膜增生性IgA肾病患者、10名局灶增生硬化性IgA肾病患者及10名正常人血清,分别经DesIgA1/Sepharose和DesDeGalIgA1/Sepharose分离,测定IgA1结合蛋白（IgA1-BP）含量及其中IgA1和IgG浓度,并检测IgA1-BP中IgA1糖基化程度,比较其在IgA肾病不同病理表型间的差别.结果 从两种亲和层析柱上所洗脱的IgA1-BP含量,在不同病理类型IgA肾病患者及正常人间无明显差别.在DesDeGalIgA1/Sepharose上洗脱的IgA1-BP中,两种病理类型IgA肾病患者IgA1唾液酸均严重缺失;在局灶增生硬化性IgA肾病患者中,IgA1分子半乳糖缺失比正常人严重.同时,局灶增生硬化性IgA肾病患者血清中与DesDeGalIgA1/Sepharose结合的IgG的含量显著多于正常人.结论 糖基化缺陷的IgA1自身聚合及与IgG聚合形成的大分子复合物可能与IgA肾病的病理表型相关.

Aggregated deglycosylated IgA1 and/or IgG and pathological phenotypes of IgA nephropathy

Objective To investigate the composition of macromolecular IgA1 and their association with different pathological phenotypes of IgAN.Methods Serum from twenty patients with IgAN with different patho- logical phenotypes(mild mesangial proliferative and focal proliferative sclerosing IgAN in ten each)and ten healthy blood donors were collected.The sere were applied to and IgA1 binding proteins(IgA1-BP)were eluted from the columns immobilized with desialylated IgA1(DesIgA1/Sepharese)or desialylated/degalactesylated IgA1(DesDe- GalIgA1/sepharose)respectively.The amounts of IgA1 and IgG,and the glycofonn of IgA1 in the IgA1-BP were detected by ELISA and compared between patients with different pathological phenotypes and normal controls.Re- sults The amounts of IgA1 in IgA1-BP eluted from both columns were significantly higher in patients with beth histological phenotypes of IgAN than those in normal controls,but no difference was found between patients with different phenotypes.In IgA1-BP eluted from DesDeGalIgA1/Sepharose,the desialyhtion of IgA1 was much pro- found in patients with both pathological phcnotypes of IgAN than that in normal controls,while the degalactosylation of IgA1 was much profound only in patients with focal proliferative sclerosing IgAN.The amount of IgG in IgA1-BP eluted from DesDeGalIgA1/Sepharose was significantly higher than that ehted from DesIgA1/sepharose only in pa- tients with focal proliferative scleresing IgAN.Furthermore,the amount of IgG in IgA1-BP eluted from DesDeGa- lIgA1/Sepharese was also significantly higher in patients with focal proliferative scleresing IgAN than that in normal control.Conclusion The macromolecular IgA1 composed of self-aggregated deglycesylated IgA1 and/or IgG may be related with pathological phenotypes of IgAN.