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Proteoglycans in haemodialysis-related amyloidosis

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Changes in extracellular matrices of articular tissue, intervertebral discs and systemic organs in patients with haemodialysis-related amyloidosis were investigated by immunohistochemical and biochemical examination of proteoglycans. Increased staining for chondroitin sulfate (CS) was detected in the amyloid deposits of all patients, ranging from early to advanced stages. Degenerative tissue changes around early-stage amyloid deposits in the intervertebral discs also showed positive staining for CS. Heparan sulfate (HS) was detected in amyloid deposits, especially in the synovial membrane. Biochemical analysis of connective tissues containing amyloid supported the immunohistochemical studies; CS was the major glycosaminoglycan species in these tissues, accounting for 55–81% of the total glycosaminoglycans. Although previous studies have stressed the importance of HS in amyloidogenesis, the present study showed that CS, which increased significantly in articular tissues associated with mechanical stress, also has a close relationship with amyloidogenesis.

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  1. 1.

    Aruga E, Ozawa H, Teraoka S, Ota K (1993) Macromolecules that are colocalized with deposits of beta2-microglobulin in haemodialysis-associated amyloidosis. Lab Invest 69: 223–230

  2. 2.

    Avnur Z, Geiger B (1984) Immunocytochemical localization of native chondroitin-sulfate in tissues and cultured cells using specific monoclonal antibody. Cell 38: 811–822

  3. 3.

    Binette P, Matsuzaki M, Calkins E, Alper R, Winzler R (1971) Carbohydrate composition of amyloid components. 137: 165–167

  4. 4.

    Bitter T, Muir H (1966) Mucopolysaccharide of whole human spleens in generalized amyloidosis. J Clin Invest 45: 963–975

  5. 5.

    Brandt KD, Skinner M, Cohen AS (1974) Characterization of the mucopolysaccharides associated with fractions of guanidine-denatured amyloid fibrils. Clin Chim Acta 55: 295–305

  6. 6.

    Campistol JM, Cases A, Torras A, Solar M, Muñoz-Gómez J, Montoliu J, López-Pedret J, Revert L (1987) Visceral involvement of dialysis amyloidosis. Am J Nephrol 7: 390–393

  7. 7.

    Caterson B, Lowther DA (1978) Changes in the metabolism of the proteoglycans from sheep articular cartilage in response to mechanical stress. Biochim Biophys Acta 540: 412–422

  8. 8.

    Caterson B, Christner JE, Baker JR (1983) Identification of a monoclonal antibody that specifically recognizes corneal and skeletal keratan sulfate. J Biol Chem 258: 8848–8854

  9. 9.

    Couchman JR, Caterson B, Christner JE, Baker JR (1984) Mapping by monoclonal antibody detection of glycosaminoglycans in connective tissues. Nature 308: 650–652

  10. 10.

    Dalferes ER, Radhakrishnamurthy B, Berenson GS (1967) Acid mucopolysaccharides of amyloid tissue. Arch Biochem Biophys 118: 284–291

  11. 11.

    Gejyo F, Odani S, Yamada T, Honma N, Saito H, Suzuki Y, Nakagawa OY, Kobayashi H, Maruyama Y, Hirasawa Y, Suzuki M, Arakawa M (1986) Beta2-microglobulin: a new form of amyloid protein associated with chronic haemodialysis. Kidney Int 30: 385–390

  12. 12.

    Gen H (1990) A clinicopathological study of cervical intervertebral discs. 1. On histopathological findings (in Japanese with English summary). J Jpn Orthop Assoc 64: 560–571

  13. 13.

    Hemingsen L, Skaarup P (1975) Beta2-microglobulin in urine and serum determined by ELISA technique. Scand J Clin Lab Invest 45: 367–371

  14. 14.

    Honma N, Gejyo F, Isemura M, Arakawa M (1988) Beta2-microglobulin binding to collagen: an amyloidogenic factor in chronic haemodialysis patients. In: Isobe, Araki, Uchino, Kito, Tsubura (eds) Amyloid and amyloidosis. Plenum Press, New York, pp 623–627

  15. 15.

    Horiguchi Y, Couchman JR, Ljubimov AV, Yamasaki H, Fine JD (1989) Distribution, ultrastructual localization, and ontogeny of the core protein of a heparan sulfate proteoglycan in human skin and other basement membranes. J Histochem Cytochem 37: 961–970

  16. 16.

    Kim IC, Franzblau C, Shirahama T, Cohen AS (1969) The effect of papain, pronase, nagarse and trypsin on isolated amyloid fibrils. Biochem Biophys Acta 181: 465–467

  17. 17.

    Kisilevsky R (1983) Amyloidosis: a familiar problem in the light of current pathogenetic developments. Lab Invest 49: 381–390

  18. 18.

    Kisilevsky R (1990) Heparan sulfate proteoglycans in amyloidogenesis: an epiphenomenon, a unique factor, or the tip of a more fundamental process? Lab Invest 63: 589–591

  19. 19.

    Kleinman KS, Coburn JW (1989) Amyloid syndromes associated with haemodialysis. Kidney Int 35: 567–575

  20. 20.

    Kure S, Yoshie O (1986) A syngeneic monoclonal antibody to murine meth-A sarcoma (HepSS-1) recognizes heparan sulfate glycosaminoglycan (HS-GAG): cell density and transformation dependent alteration in cell surface HS-GAG defined by HepSS-1. J Immunol 137: 3900–3908

  21. 21.

    Lammi M, Tammi M (1988) Densitometric assay of nanogram quantities of proteoglycans precipitated on nitrocellulose membrane with Safranin O. Anal Biochem 168: 352–357

  22. 22.

    Lyon AW, Narindrasorasak S, Young ID, Anastassiades T, Couchman JR, McCarthy KJ, Kisilevsky R (1991) Co-deposition of basement membrane components during the induction of murine splenic AA amyloid. Lab Invest 64: 785–790

  23. 23.

    Nishi S, Ogino S, Maruyama Y, Honma N, Gejyo F, Morita T, Arakawa M (1990) Electron-microscopic and immunohistochemical study of β2-microglobulin-related amyloidosis. Nephron 56: 357–363

  24. 24.

    Ohashi K, Hara M, Kawai R, Ogura Y, Honda K, Nihei H, Mimura N (1992) Cervical discs are most susceptible to beta2-microglobulin amyloid deposition in the vertebral column. Kidney Int 41: 1646–1652

  25. 25.

    Ohishi H, Skinner M, Sato-Araki N, Okuyama T, Gejyo F, Kimura A, Cohen AS, Schmid K (1990) Glycosaminoglycans of the haemodialysis-associated carpal synovial amyloid and amyloid-rich tissues and fibrils of heart, liver and spleen. Clin Chem 36: 88–91

  26. 26.

    Okayama T, Turumi K (1963) Acid mucopolysaccharide from a spleen of primary amyloidosis. Clin Chim Acta 8: 137–140

  27. 27.

    Pras M, Nevo Z, Schubert M, Rotman J, Matalon R (1971) The significance of mucopolysaccharides in amyloid. J Histochem Cytochem 19: 443–448

  28. 28.

    Puchtler H, Sweat F, Levine M (1962) On the binding of Congo red by amyloid. J Histochem Cytochem 10: 355–364

  29. 29.

    Roughley PJ, White RJ (1980) Age-related changes in the structure of the proteoglycan subunits from the human articular cartilage. J Biol Chem 255: 217–224

  30. 30.

    Shinoi J, Anderson JP, Ripellino JA, Robakis NK (1992) Chondroitin sulfate proteoglycan form of the Alzheimer's beta-amyloid precursor. J Biol Chem 267: 13819–13822

  31. 31.

    Snow AD, Kisilevsky R (1985) Temporal relationship between glycosaminoglycan accumulation and amyloid deposition during experimental amyloidosis — a histochemical study. Lab Invest 53: 37–44

  32. 32.

    Snow AD, Willmer J, Kisilevsky R (1987) A close ultrastructural relationship between sulfated proteoglycans and AA amyloid fibrils. Lab Invest 57: 687–698

  33. 33.

    Snow AD, Mar H, Nicolin D, Sekiguchi RT, Kimata K, Koike Y, Wright TN (1990) Early accumulation of heparan sulfate in neurons and in the β-amyloid protein-containing lesions of Alzheimer's disease and Dawn's syndrome. Am J Pathol 137: 1253–1270

  34. 34.

    Snow AD, Wright TN, Nochlin D, Koike Y, Kimata K, Dearmond SJ, Prusiner SB (1990) Immunolocalization of heparan sulfate proteoglycans to the prion protein amyloid plaques of Gerstmann-Straussler syndrome, Creutzfeldt-Jacob disease and scrapie. Lab Invest 63: 601–611

  35. 35.

    Sobue M, Nakashima N, Fukatsu T, Nagasaka T, Kato T, Ogura T, Takeuchi J (1988) Production and characterization of monoclonal antibody to dermatan sulfate proteoglycan. J Histochem Cytochem 36: 479–485

  36. 36.

    Stein K, Störkel W, Linke RP, Goebel HH (1987) Chemical heterogeneity of amyloid in the carpal tunnel syndrome. Virchow Arch A 412: 37–45

  37. 37.

    Sugahara K, Ohi Y, Harada T, Waard P de, Vliegenthart JFG (1992) Structural studies on sulfated oligosaccharides derived from the carbohydrate-protein linkage region of chondroitin 6-sulfate proteoglycans of shark cartilage. I. Six compounds containing 0 or 1 sulfate and /or phosphate residues. J Biol Chem 267: 6027–6035

  38. 38.

    Sunderland CA, Redman CWG, Stirrat GM (1981) Monoclonal antibodies to human syncytiotrophoblast. Immunology 43: 541–546

  39. 39.

    Sunderland CA, Bulmer JN, Lunscombe M, Redman CWG, Stirrat GM (1985) Immunohistological and biochemical evidence for a role for hyaluronic acid in the growth and development of the placenta. J Reprod Immunol 8: 197–212

  40. 40.

    Van Ypersele de Strihou C, Honhon B, Vandenbroucke JM, Huaux JP, Noël H, Maldague B (1988) Dialysis amyloidosis. Adv Nephrology 17:401–422

  41. 41.

    White AA, Panjabi MM (1978) The basic kinematics of the human spine — a review of past and current knowledge. Spine 3: 12–20

  42. 42.

    Yamagata M, Kimata K, Oike Y, Tani K, Maeda N, Yoshida K, Shinomura Y, Yoneda M, Suzuki S (1987) A monoclonal antibody that specifically recognizes a glucuronic acid 2-sulfatecontainig determinant in intact chondroitin sulfate chain. J Biol Chem 262: 4146–4152

  43. 43.

    Yanagishita M, Midura RJ and Hascall VC (1987) Proteoglycans: isolation and purification from tissue cultures. Methods in Enzymology 138: 279–289

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Correspondence to K. Ohashi.

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Ohashi, K., Hara, M., Kawai, R. et al. Proteoglycans in haemodialysis-related amyloidosis. Vichows Archiv A Pathol Anat 427, 49–59 (1995). https://doi.org/10.1007/BF00203737

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Key words

  • Amyloidosis
  • Haemodialysis
  • β2-Microglobulin
  • Proteoglycans
  • Chondroitin sulfate
  • Heparan sulfate