β2-Microglobulin Binding to Collagen : An Amyloidogenic Factor in Chronic Hemodialysis Patients

  • Noriyuki Homma
  • Fumitake Gejyo
  • Mamoru Isemura
  • Masaaki Arakawa


Recently, the increased incidence of systemic amyloidosis seen frequently in chronic hemodialysis patients has been received increasing attention. In particular, hemodialysis-associated amyloidosis has been osteoarthropathic symptoms such as carpal tunnel syndrome, trigger finger, joint pain in the shoulder and knee, and pathologic fracture of femoral head and neck. Gejyo et al.1 performed biochemical analysis of the tendosynovial amyloid causing carpal tunnel syndrome and first reported in 1985 that β2-microglobulin (B2M) is the structural protein of this amyloid. Subsequently, amyloid deposits in the synovia and in bone cysts of other joints in hemodialysis patients were proven to consist of B2M2. Clinically hemodialysis-related amyloid deposition characteristically occurs in tissues with abundant collagen fibers, such as joint and bone, and histologically, collagen fibers are in close proximity to the amyloid fibers on electron microscopy3.4.5. These finding led us to attempt to determine whether an affinity exists between B2M and collagen. Joint and bone tissues do not only contain collagens, but GAG chains such as proteoglycan and heparan sulfate as well. To establish a specific affinity of B2M for collagen, we compared the binding activity of B2M to collagen with the binding affinities of B2M to proteoglycan and heparan sulfate. Additionally, since hemodialysis-associated amyloidosis occurs in ectopic calcified tissue, such as the cardiac wall (unpublished finding), and urinary stone6, we also investigated the influence of calcium ion on binding activity of B2M to collagen.


Binding Activity Heparan Sulfate Carpal Tunnel Syndrome Systemic Amyloidosis Chronic Hemodialysis Patient 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    F. Gejyo, T. Yamada, S. Odani, Y. Nakagawa, M. Arakawa, T. Kunitomo, H. Kataoka, M. Suzuki, and K. Schmid, A new form of amyloid protein associated with chronic hemodialysis was identified as β2-microglobulin, Biochem. Biophys. Res. Commun. 129:701 (1985).CrossRefGoogle Scholar
  2. 2.
    P. D. Gorevic, T. T. Casey, W. J. Stone, C. R. DiRaimondo, F. C. Prelli, and B. Fragione, Beta-2 Microglobulin is an amyloidogenic protein in man, J. Clin. Invest. 76:2425 (1985).CrossRefGoogle Scholar
  3. 3.
    T. Bardin, D. Kuntz, J. Zingraff, M. C. Voisin, A. Zelmar, and J. Lansaman, Synovial amyloidosis in patients undergoing long-term hemodialysis, Arthritis Rheum. 28:1052 (1985).CrossRefGoogle Scholar
  4. 4.
    C. Ladefoged, O. Fedders, and O. F. Petersen, Amyloid in interverteveral discs: a histopathological investigation of surgical material from 100 consecutive operation on herniated discs, Ann. Rheum. Dis. 45:239 (1986).CrossRefGoogle Scholar
  5. 5.
    A. Z. Fenves, M. Emmett, M. G. White, G. Greenway, and D. B. Michaels, Carpal tunnel syndrome with cystic bone lesions secondary to amyloidosis in chronic hemodialysis patients, Am. J. Kidney Dis. VII:130 (1986).Google Scholar
  6. 6.
    J. Bommer, R. Waldherr and E. Ritz, Kidney lesions in uraemic patients and β2-microglobulin derived amyloid, The Lancet Dec. 21/28:1437 (1985).CrossRefGoogle Scholar
  7. 7.
    F. Gejyo, N. Homma, Y. Suzuki, and M. Arakawa, Serum levels of β2-microglobulin as a new form of amyloid protein in patients undergoing long-term hemodialysis, N. Engl. J. Med. 314:585 (1986).CrossRefGoogle Scholar
  8. 8.
    P. Ericson, Agglutination of Streptococcus mutans by Low-Molecular-Weight Salivary Components: Effect of β2-Microglobulin, Infect. Immun. 46:526 (1984).Google Scholar
  9. 9.
    L. Fesüs, A. Falus, A. Erdei, and K. Laki, Human β2-microglobulin is a substrate of tissue transglutaminase: Polymerization in solution and on the cell surface, J. Cell Biol. 89:706 (1981).CrossRefGoogle Scholar
  10. 10.
    D. Ericson, D. Bratthall, L. Björck, E. Myhre, and G. Kronvall, Interactions between human serum proteins and oral streptococci reveal occurence of receptors for aggregated β2-microglobulin, Infect. Immun. 25:279 (1979).Google Scholar
  11. 11.
    L. Lögdberg, L. Björck, Binding of mammalian β2-microglobulin by glycoproteins in fish serum, Mol. Immunol. 20:885 (1983).CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1988

Authors and Affiliations

  • Noriyuki Homma
    • 1
  • Fumitake Gejyo
    • 1
  • Mamoru Isemura
    • 2
  • Masaaki Arakawa
    • 1
  1. 1.Department of Medicine(II)Niigata University School of MedicineNiigata 951Japan
  2. 2.Laboratory of Biochemistry, School of Food and Nutritional SciencesThe University of ShizuokaShizuoka 422Japan

Personalised recommendations