Background: 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.
Methods: 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.
Results: 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).
Conclusion: 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.