Linke R P, Kerling A, Rail A
Max-Planck-Institut für Biochemie, Martinsried, München, Germany.
Kidney Int Suppl. 1993 Jun;41:S100-5.
Amyloid deposits of patients on long-term hemodialysis consist of a considerable proportion of beta 2-microglobulin (beta 2m) fragments, as demonstrated by N-terminal amino acid sequence analysis of isolated amyloid fibril proteins. Since this finding may have pathogenetic relevance, we have produced fragment-specific antibodies directed against a synthetic peptide of beta 2m (P132) commencing at position 20. Absorption of this antiserum on insolubilized beta 2m and subsequent isolation of the anti-P132 antibody from the insolubilized P132 peptide yielded a cleavage site-specific antibody which reacted only with P132, but not with a control fragment of beta 2m and only marginally with a beta 2m preparation in micro-ELISA. When applied onto tissue sections from various organs with AB-amyloid using an immunoperoxidase method, the fragment-specific anti-P132 antibody reacted immunohistochemically predominantly with renal AB-amyloid stones, but not with all amyloid from large joints and bone marrow amyloid-tumors, in contrast to an anti-AB or beta 2m-antibodies, which intensely stained all deposits. Thus, the presence of fragmented beta 2m-molecules have been demonstrated in amyloid in tissue sections. These data are in accordance with the results of chemical studies.
长期血液透析患者的淀粉样沉积物含有相当比例的β2-微球蛋白（β2m）片段，这通过对分离出的淀粉样纤维蛋白进行N端氨基酸序列分析得到证实。由于这一发现可能具有致病相关性，我们制备了针对β2m（P132）从第20位开始的合成肽的片段特异性抗体。用不溶性β2m吸附该抗血清，随后从不溶性P132肽中分离抗P132抗体，得到了一个切割位点特异性抗体，该抗体仅与P132反应，不与β2m的对照片段反应，在微量ELISA中与β2m制剂的反应也很微弱。当使用免疫过氧化物酶方法应用于来自各种器官的伴有AB淀粉样变的组织切片时，片段特异性抗P132抗体免疫组化主要与肾AB淀粉样结石反应，但与来自大关节的所有淀粉样变和骨髓淀粉样肿瘤不反应，这与抗AB或β2m抗体不同，后者能强烈染色所有沉积物。因此，在组织切片的淀粉样变中已证实存在片段化的β2m分子。这些数据与化学研究结果一致。
