Motomiya Yoshihiro, Ando Yukio, Haraoka Katsuki, Sun Xuguo, Iwamoto Hisahiko, Uchimura Tomonori, Maruyama Ikuro
Suiyukai Clinic, Kashihara, Nara, Japan.
Kidney Int. 2003 Dec;64(6):2244-52. doi: 10.1046/j.1523-1755.2003.00315.x.
The presence of alpha2-macroglobulin (alpha2M) in amyloid tissue from patients with dialysis-related amyloidosis (DRA) was demonstrated by Argilés et al in 1989. Thereafter, the formation of the complex of beta2-microglobulin (beta2m) with alpha2m was confirmed directly by in vitro study. In Alzheimer's disease, complex formation of amyloid beta-peptide and alpha2M is considered to play an important role in the pathogenesis by modifying the degradation processes of amyloid protein. Thus, we hypothesized that the alpha2M-beta2m complex is an important factor in the pathogenesis of DRA as well. Here, we measured the circulating levels of alpha2M-beta2m complex in the maintenance hemodialysis patients and discussed about its clinical significance in DRA.
One hundred and thirty-seven hemodialysis patients and 11 prehemodialysis chronic renal failure (CRF) patients were included in this study. The affinity of purified alpha2M for beta2m was confirmed by a highly sensitive 27 MHz quartz crystal microbalance (QCM). The presence of circulating alpha2M-beta2m complex was analyzed by immunoblotting analysis. Furthermore, the serum levels of alpha2M-beta2m complex were measured by sandwich enzyme immunoassay.
QCM analysis revealed the high affinity of alpha2M for beta2m. The presence of circulating alpha2M-beta2m complex was detected in two out of a total 11 prehemodialysis CRF patients and in 95 out of the total of 137 hemodialysis patients. None of the healthy subjects, however, were observed to present with any alpha2M-beta2m complex. Serum levels of the alpha2M-beta2m complex were correlated to the duration of hemodialysis (P= 0.043). Serum levels of the alpha2M-beta2m complex were significantly higher in patients with high DRA score than in patients with negative DRA score (P= 0.018). Moreover, serum levels of the alpha2M-beta2m complex showed significantly lower in the hemodiafiltration patients compared to the hemodialysis patients (P= 0.002) and showed a strong correlation with DRA score in hemodialysis patients excluding 11 hemodiafiltration patients (P= 0.0004).
This study is the first to demonstrate the presence of circulating alpha2M-beta2m complex in hemodialysis patients. Furthermore, we observed the correlation between serum levels of alpha2M-beta2m complex and clinical characteristics of DRA. Thus we concluded that a formation of an alpha2M-beta2m complex may be implicated in DRA.
1989年，阿吉莱斯等人证实了透析相关性淀粉样变性（DRA）患者的淀粉样组织中存在α2-巨球蛋白（α2M）。此后，体外研究直接证实了β2-微球蛋白（β2m）与α2m形成复合物。在阿尔茨海默病中，淀粉样β肽与α2M形成复合物被认为通过改变淀粉样蛋白的降解过程在发病机制中起重要作用。因此，我们推测α2M-β2m复合物也是DRA发病机制中的一个重要因素。在此，我们测量了维持性血液透析患者循环中α2M-β2m复合物的水平，并探讨了其在DRA中的临床意义。
本研究纳入了137例血液透析患者和11例血液透析前慢性肾衰竭（CRF）患者。通过高灵敏度的27MHz石英晶体微天平（QCM）证实了纯化的α2M与β2m的亲和力。通过免疫印迹分析检测循环中α2M-β2m复合物的存在。此外，采用夹心酶免疫测定法测量α2M-β2m复合物的血清水平。
QCM分析显示α2M与β2m具有高亲和力。在11例血液透析前CRF患者中的2例以及137例血液透析患者中的95例检测到循环中α2M-β2m复合物的存在。然而，未观察到任何健康受试者存在α2M-β2m复合物。α2M-β2m复合物的血清水平与血液透析时间相关（P = 0.043）。DRA评分高的患者中α2M-β2m复合物的血清水平显著高于DRA评分为阴性的患者（P = 0.018）。此外，血液透析滤过患者中α2M-β2m复合物的血清水平显著低于血液透析患者（P = 0.002），并且在排除11例血液透析滤过患者的血液透析患者中，其与DRA评分呈强相关（P = 0.0004）。
本研究首次证实在血液透析患者中存在循环α2M-β2m复合物。此外，我们观察到α2M-β2m复合物的血清水平与DRA的临床特征之间存在相关性。因此，我们得出结论，α2M-β2m复合物的形成可能与DRA有关。
