Synthesis of beta 2-microglobulin in lymphocyte culture: role of hemodialysis, dialysis membranes, dialysis-amyloidosis, and lymphokines.

Dialysis-amyloidosis (A beta 2M) is a recently recognized chronic complication in long-term dialysis patients, apparently effecting 5% to 10% of all dialysis patients. In 1985, Gejyo et al (Biochem Biophys Res Commun 129:701-706, 1085) and Shirahama et al (Lab Invest 53:705-709, 1985) identified beta 2-microglobulin (beta 2-M) as the major constituent protein of this unique type of systemic amyloidosis. The specific pathogenesis of A beta 2M remains unknown, although beta 2-M has been clearly identified as playing a central role as the amyloidogenic protein. To investigate the factors responsible for in vitro beta 2-M synthesis, we studied beta 2-M production by lymphocyte cultures obtained from dialysis patients and grown under a variety of different conditions, and compared the results to a control group of subjects with normal renal function. We could not demonstrate any stimulatory influence on beta 2-M synthesis by the hemodialysis treatment, the type of dialysis membrane used, or the clinical presence of A beta 2M. Rather, dialysis membranes, sterilized with ethylene oxide or gamma rays, added to the lymphocyte cultures exerted a strong dose-dependent inhibitory effect on beta 2-M synthesis. From the results of this study, we conclude that peripheral blood lymphocytes in uremic patients synthesize beta 2-M normally and that the direct interaction between circulating lymphocytes and the dialysis membrane that occurs during hemodialysis does not seem to contribute directly to beta 2-M synthesis.