β2-microglobulin: A new form of amyloid protein associated with chronic hemodialysis

Abstract

Carpal tunnel syndrome (CTS) has been associated with amyloid deposits and is now regarded as a major complication in chronic hemodialysis patients. While this new syndrome has been receiving increasing attention, its etiology has not been clarified. We have isolated amyloid fibrils from amyloid laden tissues inside the carpal tunnel in four different hemodialysis patients with CTS. After solubilization in guanidine HCl, a significant amount of the protein was located in a homogeneous, low molecular weight fraction. Each protein was found to be identical to beta 2-microglobulin with regard to its molecular weight of 11,000 on SDS-PAGE, amino acid composition and N-terminal amino acids: Ile-Gln-Arg-Thr-Pro-Lys-Ile-Gln-Val-Tyr-Ser-Arg-His-Pro-Ala-Glu. In direct immunofluorescent study, anti-beta 2-microglobulin did react positively with amyloid deposits. These results demonstrate that the amyloid associated with chronic hemodialysis contains as major component a new form of amyloid fibril protein that is homologous to beta 2-microglobulin. It is postulated that beta 2-microglobulin cannot be removed from the blood by conventional hemodialysis, and accumulates in tissues causing the formation of amyloid fibrils, which, having a relatively high affinity to the carpal tunnel area, thus causes CTS.

Beta-2 microglobulin is an amyloidogenic protein in man.

“…A recent detailed x- I ray crystallographic study (17) (27 (29) have recently reported amino acid sequence data to show that beta-2-miproglobulin was a subunit protein present in amyloid isolated from the carpal tunnel of a patient on chronic dialysis, thus providing independent corroboration of our findings.…”

Carpal-tunnel syndrome in hemodialysis: Syndrome diagnosed in 8 of 60 patients

“…Compromise of the median nerve in the carpal-tunnel in this patient might have occurred subclinically as a result of severe peripheral uremic neuropathy, even after adequate decompression. There was no difference between the values for serum R-2 microglobulin of CTS patients and those of non-CTS patients in our series, which is in accordance with the past report by Gejyo et al (1986b). They suggested that some factors other than the level of serum 8-2 microglobulin, such as calcium or sulfated glucose of aluminum, might play an important role in the mechanism where amyloid is deposited in human tissues, though amyloid deposits in hemodialyzed patients consist mainly of 8-2 microglobulin itself, In half of the specimens derived from the transverse carpal ligaments of our operated patients, amyloid deposits were identified.…”

Involvement of beta 2-microglobulin modified with advanced glycation end products in the pathogenesis of hemodialysis-associated amyloidosis. Induction of human monocyte chemotaxis and macrophage secretion of tumor necrosis factor-alpha and interleukin-1.

“…The serum f2M level is markedly higher (usually > 30-fold) in these patients as compared with healthy individuals (5). However, there is no statistical correlation between the serum concentration of ,32M and the occurrence of HAA (5), thereby suggesting that the pathogenesis of HAA is not accounted for merely by an increase in the serum f2M level.…”