Capillary electrophoretic profile of β2-microglobulin intermediate associated with hemodialysis.

We previously identified an intermediate β(2)-microglobulin (I-β(2) m), which is an amyloidogenic β(2) m variant, via capillary electrophoresis (CE) and reported hemodialysis (HD)-associated variations in the serum concentrations of each β(2) m component, including that found in the rebound phase. Recent research has indicated that I-β(2) m can bind, via the SO(3)(-) moiety, with glycosaminoglycan or proteoglycan, which are major components of interstitial tissue. Because alterations in I-β(2) m are likely to be important in view of the possible accumulation of amyloidogenic precursor proteins in the interstitial space, we studied the I-β(2) m profile as related to HD. We used CE to determine the I-β(2) m profile both at the start and at the end of HD and during the rebound phase in 12 HD patients. We found both an unfolded β(2) m and a destructured I-β(2) m. More important, two peaks appeared in the rebound phase, one suggesting a refolding and one suggesting an irreversible destruction. Given that the intercompartmental transfer coefficient for β(2) m is 1.0, our results indicated concomitant processes occurring after HD: refolding of the β(2) m conformation and trapping of destructured I-β(2) m in the extravascular space. Because the trapping of destructured I-β(2) m supposedly leads to accumulation of β(2) m in the interstitial space, we have proposed a new concept-a "shuttle" concept-for amyloid formation from β(2) m in the HD setting.