Abstract
Sjögren's syndrome (SS) is an autoimmune disease, and some patients have been found to have SS complicated with rheumatoid arthritis (RA), in which IgG is known to carry abnormal N-linked oligosaccharides. In order to investigate the relationship between SS and RA, the structures of N-linked oligosaccharides of IgG from 12 primary SS patients without RA, 9 RA patients, and 8 healthy individuals were analyzed using reversed-phase high-performance liquid chromatography, in combination with sequential exoglycosidase treatment and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. All of the IgG samples obtained from primary SS patients, RA patients, and healthy individuals contained the same series of biantennary complex-type oligosaccharides, but the ratio of each oligosaccharide differed among these 3 groups. The incidence of galactose-lacking N-linked oligosaccharides obtained from the IgG of RA patients was significantly higher than that from healthy individuals, but that from the serum IgG of primary SS patients varied among individuals. The patients with primary SS were classified into two groups based on the galactosylation levels of IgG oligosaccharides; one group exhibits galactosylation levels as low as those of RA patients and another exhibits levels similar to those of healthy individuals. Measurement of levels of rheumatoid factor (RF) revealed that primary SS patients with a high incidence of RF belonged to the low galactosylation group, as did RA patients. These results suggest that appearance of IgG carrying abnormal N-linked oligosaccharides in primary SS may be related to future complication with RA.
Similar content being viewed by others
References
Mizuochi T, Taniguchi T, Simizu A, Kobata A, Structural and numerical variations of the carbohydrate moiety of immunoglobulin G, J Immunol 129, 2016–20 (1982).
Barker RN, Leader KA, Elson CJ, Serial changes in the galactosylation of autoantibodies and serum IgG in autoimmune haemolytic anaemia, Autoimmunity 31, 103–8 (1999).
Bond A, Alavi A, Axford JS, Youinou P, Hay FC, The relationship between exposed galactose and N-acetylglucosamine residues on IgG in rheumatoid arthritis (RA), juvenile chronic arthritis (JCA) and Sjogren's syndrome (SS), Clin Exp Immunol 105, 99–103 (1996).
Bond A, Alavi A, Axford JS, Bourke BE, Bruckner FE, Kerr MA, Maxwell JD, Tweed KJ, Weldon MJ, Youinou P, Hay FC, A detailed lectin analysis of IgG glycosylation, demonstrating disease specific changes in terminal galactose and N-acetylglucosamine, J Autoimmun 10, 77–85 (1997).
Mizuochi T, Hamako J, Nose M, Titani K, Structural changes in the oligosaccharide chains of IgG in autoimmune MRL/Mp-lpr/lpr mice, J Immunol 145, 1794–8 (1990).
Parekh RB, Roitt IM, Isenberg DA, Dwek RA, Ansell BM, Rademacher TW, Galactosylation of IgG associated oligosaccharides: Reduction in patients with adult and juvenile onset rheumatoid arthritis and relation to disease activity, Lancet i, 966–9 (1988).
Parekh R, Isenberg D, Rook G, Roitt I, Dwek R, Rademacher T, A comparative analysis of disease-associated changes in the galactosylation of serum IgG, J Autoimmun 2, 101–14 (1989).
Tang W, Matsumoto A, Shikata K, Takeuchi F, Konishi T, Nakata M, Mizuochi T, Detection of disease-specific augmentation of abnormal immunoglobulin G in sera of patients with rheumatoid arthritis, Glycoconjugate J 15, 929–34 (1998).
Watson M, Rudd PM, Bland M, Dwek RA, Axford JS, Sugar printing rheumatic diseases: A potential method for disease differentiation using immunoglobulin G oligosaccharides, Arthritis Rheum 42, 1682–90 (1999).
Youinou P, Pennec YL, Casburn-Budd R, Dueymes M, Letoux G, Lamour A, Galactose terminating oligosaccharides of IgG in patients with primary Sjogren's syndrome, J Autoimmun 5, 393–400 (1992).
Mizuochi T, Taniguchi T, Nagano Y, Takeuchi F, Matsuta K, Miyamoto T, Kobata A, Abnormal patterns of the sugar chains of immunoglobulin G from patients with RA, Ryumachi 24, 581 (1984).
Parekh RB, Dwek RA, Sutton BJ, Fernandes DL, Leung A, Stanworth D, Rademacher TW, Mizuochi T, Taniguchi T, Matsuta K, Takeuchi F, Nagano Y, Miyamoto T, Kobata A, Association of rheumatoid arthritis and primary osteoarthritis with changes in the glycosylation pattern of total serum IgG, Nature 316, 452–7 (1985).
Tomana M, Schrohenloher RE, Koopman WJ, Alarcon GS, Paul WA, Abnormal glycosylation of serum IgG from patients with chronic inflammatory diseases, Arthritis Rheum 31, 333–8 (1988).
Fox RI, Sjogren's syndrome. In Textbook of Rheumatology, 5th edn. edited by Kelley WN, Harris ED Jr, Ruddy S, Sledge CB (WB Saunders Company, Philadelphia, 1997), pp. 955–71.
Jonsson R, Haga HJ, Gordon TP, Sjogren's syndrome. In Arthritis and Allied Conditions, edited by Koopman WJ (Lippincott Williams & Wilkins, Philadelphia, 2001), pp. 1736–59.
Arnett FC, Edworthy SM, Bioch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kalplan SR, Liang MH, Luthar HS, Medsger TA Jr, Mitchell DM, Neustadt DH, Pinals RS, Schaller JG, Sharp JT, Wilder RL, Hunder GG, The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis, Arthritis Rheum 31, 315–24 (1988).
Vitali C, Bombardieri S, Moutsopoulos HM, Balestrieri G, Bencivelli W, Bernstein RM, Bjerrum KB, Braga B, Coll J, Vita S, Drosos AA, Herenfeld M, Hatron PY, Hay EM, Isenberg DA, Janin A, Kalden JR, Kater L, Konttinen Y, Maddison PJ, Maini, RN, Manthorpe R, Meyer O, Ostuni P, Penned Y, Prause JU, Richards A, Sauvezie B, Schiodt M, Sciuto M, Scully C, Shoenfeld Y, Skopouli FN, Smolen JS, Snaith ML, Tishler M, Todesco S, Valensini G, Venables PJW, Wattiaux MJ, Youinou P, Preliminary criteria for the classification of Sjogren's syndrome. Results of a prospective concerned action supported by European Community, Arthritis Rheum 36, 340–7 (1993).
Mizuochi T, Taniguchi T, Asami Y, Takamatsu J, Okuda M, Iwanaga S, Kobata A, Comparative studies on structures of the carbohydrate moieties of human fibrinogen and abnormal fibrinogen Nagoya, J Biochem (Tokyo) 92, 283–93 (1982).
Matsumoto A, Shikata K, Takeuchi F, Kojima N, Mizuochi T, Autoantibody activity in IgG rheumatoid factor increases with decreasing levels of galactosylation and sialylation, J Biochem (Tokyo) 128, 621–8 (2000).
Shikata K, Yasuda T, Takeuchi F, Konishi T, Nakata M, Mizuochi T, Structural changes in oligosaccharide moiety of human IgG with aging, Glycoconjugate J 15, 683–9 (1998).
Mizuochi T, Hamako J, Titani K, Structures of the sugar chains of mouse immunoglobulin G, Arch Biochem Biophys 257, 387–94 (1987).
Li YT, Li SC, α-Mannosidase, β-N-acetylhexosaminidase and β-galactosidase from jack bean meal, Methods Enzymol 28, 702–13 (1972).
Matsui T, Titani K, Mizuochi T, Structures of the asparagine-linked oligosaccharide chains of human von Willebrand factor, J Biol Chem 267, 8723–31 (1992).
Kuroda Y, Nakata M, Hirose S, Shirai T, Iwamoto M, Izui S, Kojima N, Mizuochi T, Abnormal IgG galactosylation in MRL-lpr/lpr mice: Pathogenic roles on the development of arthritis, Pathol Int 51, 909–15 (2001).
Mizuochi T, Microscale sequencing of N-linked oligosaccharides of glycoproteins using hydrazinolysis, Bio-Gel P-4, and sequential exoglycosidase digestion, in Method in Molecular Biology Vol. 14: Glycoprotein Analysis in Biomedicine, edited by Hounsell E (Humana Press, Totowa, 1993), pp. 55–68.
Laemmli UK, Cleavage of structural proteins during the assembly of the head of bacteriophage T4, Nature 227, 680–5 (1970).
Shimizu Y, Nakata M, Kuroda Y, Tsutsumi F, Kojima N, Mizuochi T, Rapid and simple preparation of N-linked oligosaccharides by cellulose chromatography, Carbohydrate Res 332, 381–8 (2001).
Ichikawa Y, Yamada C, Horiki T, Hoshina Y, Uchiyama M, Yamada Y, Toumatu J, Anti-agalactosyl IgG antibodies and isotype profiles of rheumatoid factors in Sjogren's syndrome and rheumatoid arthritis, Clin Exp Rheumatol 16, 709–15 (1998).
Mizuochi T, Reactant to rheumatoid factor: Abnormality in the sugar chains of IgG in patients with rheumatoid arthritis (in Japanese), Rinshomeneki 17, 977–84 (1985).
Davidson KS, Kelley CA, Griffiths ID, Primary Sjogren's syndrome in the north east of England: A long-term follow-up study, Rheumatology 38, 245–53 (1999).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kuroda, Y., Nakata, M., Makino, A. et al. Structural studies on IgG oligosaccharides of patients with primary Sjögren's syndrome. Glycoconj J 19, 23–31 (2002). https://doi.org/10.1023/A:1022528829799
Issue Date:
DOI: https://doi.org/10.1023/A:1022528829799