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Recent advances in understanding molecular mechanisms in the pathogenesis and antibody profile of Sjögren’s syndrome

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Abstract

Sjögren’s syndrome is a chronic autoimmune and rheu-matic disorder of the mucous membranes caused by a lack of proper exocrine secretions, with prominent sicca complaints. The molecular mechanisms of the pathogene-sis are virtually unknown, although progress has been made with regard to chemokines, B cell activating factor, and apoptosis. A large number of autoantibodies have been reported in Sjögren’s syndrome, some of which relate to impairment of glandular function. Sjögren’s syn-drome is a female-dominant disease with a late age of onset; most patients contract the disease at the age of 40 to 50 years. Lately, attention has been drawn to the effects of adrenopause in Sjögren’s syndrome and on dehydroepiandrosterone and its intracrine metabolism in target tissues. This can influence the maintenance and remodeling of exocrine glands and may explain, in part, another important disease symptom—fatigue.

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References and Recommended Reading

  1. Jonsson R, Haga H-J, Gordon T: Sjögren’s syndrome. In Arthri-tis and Allied Conditions: A Textbook of Rheumatology, edn 14. Edited by Koopman WJ. Philadelphia: Lippincott Williams & Wilkins; 2001:1736–1759.

    Google Scholar 

  2. Bolstad AI, Jonsson R: Genetic aspects of Sjögren’s syndrome. Arthritis Res 2002, 4:353–359.

    Article  PubMed  Google Scholar 

  3. Cha S, Peck AB, Humphreys-Beher MG: Progress in understand-ing autoimmune exocrinopathy using the non-obese diabetic mouse: an update. Crit Rev Oral Biol Med 2002, 13:5–16.

    Article  PubMed  CAS  Google Scholar 

  4. James JA, Harley JB, Scofield RH: Role of viruses in systemic lupus erythematosus and Sjögren’s syndrome. Curr Opin Rheumatol 2001, 13:370–376.

    Article  PubMed  CAS  Google Scholar 

  5. Vitali C, Bombardieri S, Jonsson R, et al.: Classification criteria for Sjögren’s syndrome: a revised version of the European criteria proposed by the American-European consensus group. Ann Rheum Dis 2002, 61:554–558.

    Article  PubMed  CAS  Google Scholar 

  6. Kapsogeorgou EK, Moutsopoulos HM, Manoussakis MN: Func-tional expression of a costimulatory B7.2 (CD86) protein on human salivary gland epithelial cells that interacts with the CD28 receptor, but has reduced binding to CTLA4. J Immunol 2001, 166:3107–3113. This paper presents further evidence for a local antigen-presenting mechanism is SS, a process often designated autoimmune epithelitis by this group. Epithelial cells may play a critical role in the regulation of local immune responses.

    PubMed  CAS  Google Scholar 

  7. Magnusson V, Nakken B, Bolstad AI, Alarcón-Riquelme M: Cytokinepolymorphisms in systemic lupus erythematosus and Sjögren’s syndrome. Scand J Immunol 2001, 54:55–61.

    Article  PubMed  CAS  Google Scholar 

  8. Ma J, Chen T, Mandelin J, et al.: Regulation of macrophage activation. Cell Mol Life Sci 2003, In press.

  9. Koski H, Janin A, Humphreys-Beher MG, et al.: Tumor necrosis factor-alpha and receptors for it in labial salivary glands in Sjögren’s syndrome. Clin Exp Rheumatol 2001, 19:131–137.

    PubMed  CAS  Google Scholar 

  10. Steinfeld SD, Demols P, Salmon I, et al.: Infliximab in patients with primary Sjögren’s syndrome: a pilot study. Arthritis Rheum 2001, 44:2371–2375. This is the first study using biologic treatment by modulating TNF production in SS.

    Article  PubMed  CAS  Google Scholar 

  11. Steinfeld SD, Appelboom T, Delporte C: Treatment with inflix-imab restores normal aquaporin 5 distribution in minor sal-ivary glands of patients wih Sjögren’s syndrome. Arthrisis Rheum 2002, 46:2249–2251.

    Article  Google Scholar 

  12. Amft N, Curnow S, Scheel-Toellner D, et al.: Ectopic expression of the B cell-attracting chemokine BCA-1 (CXCL13) on endothelial cells and within lymphoid follicles contributes to the establishment of germinal center-like structures in Sjögren’s syndrome. Arthritis Rheum 2001, 44:2633–2641.

    Article  PubMed  CAS  Google Scholar 

  13. Xanthou G, Polihronis M, Tzioufas A, et al.: "Lymphoid" chemokine messenger RNA expression by epithelial cells in the chronic inflammatory lesion of the salivary glands of Sjögren’s syndrome patients: possible participation in lym-phoid structure formation. Arthritis Rheum 2001, 44:408–418.

    Article  PubMed  CAS  Google Scholar 

  14. Salomonsson S, Larsson P, Tengner P, et al.: Expression of the B cell-attracting chemokine CXCL13 in the target organ and autoantibody production in ectopic lymphoid tissue in the chronic inflammatory disease Sjögren’s syndrome. Scand J Immunol 2002, 55:336–342.

    Article  PubMed  CAS  Google Scholar 

  15. Ogawa N, Ping L, Zhenjun L, et al.: Involvement of the inter-feron- gamma-induced T cell-attracting chemokines, inter-feron- gamma-inducible 10-kd protein (CXCL10) and monokine induced by interferon-gamma (CXCL9), in the sal-ivary glands of patients with Sjögren’s syndrome. Arthritis Rheum 2002, 46:2730–2741.

    Article  PubMed  CAS  Google Scholar 

  16. Salomonsson S, Jonsson MV, Skarstein K, et al.: Cellular basis of ectopic germinal center formation and autoantibody pro-duction in the target organ of patients with Sjögren’s syn-drome. Arthritis Rheum 2003, In press. This study has identified germinal center-like structures in a cohort of unselected labial salivary gland biopsies combined with the pattern of chemokine expression and autoantibody production.

  17. Törnwall J, Konttinen YT, Tuominen RK, Törnwall M: Protein kinase C expression in salivary gland acinar epithelial cells in Sjögren’s syndrome. Lancet 1997, 349:1814–1815.

    Article  PubMed  Google Scholar 

  18. Groom J, Kalled SL, Cutler AH, et al.: Association of BAFF/BlyS overexpression and altered B cell differentiation with Sjögren’s syndrome. J Clin Invest 2002, 109:59–68. The first study drawing attention to the potential role of BAFF in SS, which has been further studied by Szodoray et al. [20], where it was shown that BAFF directs the life span of infiltrating B cells.

    Article  PubMed  CAS  Google Scholar 

  19. Mariette X, Roux S, Zhang J, et al.: The level of BlyS (BAFF) cor-relates with the titer of autoantibodies in Sjögren’s syn-drome. Ann Rheum Dis 2003, 62:168–171.

    Article  PubMed  CAS  Google Scholar 

  20. Szodoray P, Jellestad S, Ohlsson M, Jonsson R: Attenuated apo-ptosis of B cell activating factor (BAFF) expressing cells in Sjögren’s syndrome. Lab Invest 2003, 83:357–365.

    Article  PubMed  CAS  Google Scholar 

  21. Ohlsson M, Skarstein K, Bolstad AI, et al.: Fas-induced apopto-sis is a rare event in Sjögren’s syndrome. Lab Invest 2001, 81:95–105.

    PubMed  CAS  Google Scholar 

  22. Ohlsson M, Szodoray P, Lako Loro L, et al.: CD40, CD154, bax and bcl-2 expression in Sjögren’s syndrome salivary glands: a putative anti-apoptotic role during its effector phases. Scand J Immunol 2002, 56:561–571.

    Article  PubMed  CAS  Google Scholar 

  23. Bolstad AI, Eiken HG, Rosenlund B, et al.: Increased salivary gland tissue expression of Fas, Fas ligand, cytotoxic T-lympho-cyte antigen 4, and programmed cell death 1 protein in pri-mary Sjögren’s syndrome. Arthritis Rheum 2003, 48:174–185. This is the first study presented that has used real-time polymerase chain reaction technology for quantification of central molecules in the apoptotic process and immune reaction in SS. It demonstrates a substantial increase in negative regulator molecules: programmed cell death-1 and cytokine T lymphocyte antigen-4.

    Article  PubMed  CAS  Google Scholar 

  24. Ohlsson M, Jonsson R, Brokstad KA: Subcellular redistribu-tion and surface exposure of the Ro52, Ro60 and La48 autoantigens during apoptosis in human ductal epithelial cells: a possible mechanism in the pathogenesis of Sjögren’s syndrome. Scand J Immunol 2002, 56:456–469. This study presents evidence for surface exposure of autoantigens on cultured ductal epithelial cells during induced apoptosis. Such redis-tribution could make autoantigens more accessible for immune cells and antigen presentation.

    Article  PubMed  CAS  Google Scholar 

  25. McArthur C, Wang Y, Veno P, et al.: Intracellular trafficking and surface expression of SS-A (Ro), SS-B (La), poly (ADP-ribose) polymerase and a-fodrin autoantigens during apop-tosis in human salivary gland cells induced by tumor necro-sis factor-a. Arch Oral Biol 2002, 47:443–448.

    Article  PubMed  CAS  Google Scholar 

  26. Dörner T, Lipksy PE: Immunoglobulin variable-region gene usage in systemic autoimmune diseases. Arthritis Rheum 2001, 44:2715–2727.

    Article  PubMed  Google Scholar 

  27. Nakken B, Jonsson R, Brokstad K, et al.: Associations of MHC class II alleles in Norwegian primary Sjögren’s syndrome patients: Implications for development of autoantibodies to the Ro52 autoantigen. Scand J Immunol 2001, 54:428–433.

    Article  PubMed  CAS  Google Scholar 

  28. Jonsson R, Brokstad KA, Lipsky PE, Zouali M: B lymphocyte selection and autoimmunity. Tre nds I mmunol 2001, 22:653–654.

    CAS  Google Scholar 

  29. Bohnhorst JØ, Bjørgan MB, Thoen JE, et al.: Abnormal B cell differentiation in primary Sjögren’s syndrome results in a depressed percentage of circulating memory B cells and ele-vated levels of soluble CD27 that correlate with serum IgG concentration. Clin Immunol 2002, 103:79–88. The abnormal differentiation of B cells to plasma cells is common in the glandular lesions of patients with SS. In this study, it is shown a depression of the circulating memory B cell pool and release of signif-icant amounts of soluble CD27.

    Article  PubMed  CAS  Google Scholar 

  30. Hansen A, Odendahl M, Reiter K, et al.: Diminished peripheral blood memory B cells and accumulation of memory B cells in the salivary glands of patients with Sjögren’s syndrome. Arthritis Rheum 2002, 46:2160–2171.

    Article  PubMed  CAS  Google Scholar 

  31. Dörner T, Lipsky PE: Abnormalities of B cell phenotype, immunoglobulin gene expression and the emergence of autoimmunity in Sjögren’s syndrome. Arthritis Res 2002, 4:360–371.

    Article  PubMed  Google Scholar 

  32. Gordon TP, Bolstad AI, Rischmueller M, et al.: Autoantibodies in primary Sjögren’s syndrome: new insights into mecha-nisms of autoantibody diversification and disease pathogen-esis. Autoimmunity 2001, 34:123–132.

    Article  PubMed  CAS  Google Scholar 

  33. Goldblatt F, Gordon TP, Waterman SA: Autoantibody-mediated gastrointestinal dysmotility in scleroderma. Gastroenterology 2002, 123:1144–1150.

    Article  PubMed  CAS  Google Scholar 

  34. Berra A, Sterin-Borda L: Role of salivary IgA in the pathogene-sis of Sjögren’s syndrome. Clinical Immunol 2002, 104:49–57.

    Article  CAS  Google Scholar 

  35. Beroukas D, Goodfellow R, Hiscock J, et al.: Up-regulation of M3-muscarinic receptors in labial salivary gland acini in pri-mary Sjögren’s syndrome. Lab Invest 2002, 82:203–210.

    PubMed  CAS  Google Scholar 

  36. Bacman S, Berra A, Sterin-Borda L, et al.: Muscarinic acetylcho-line receptor antibodies as a new marker of dry eye Sjögren’s syndrome. Invest Ophthalmol Vis Sci 2001, 42:321–327.

    PubMed  CAS  Google Scholar 

  37. Cavill D, Waterman SA, Gordon TP: Failure to detect antibod-ies to extracellular loop peptides of the musccarinic M3 receptor in primary Sjögren’s syndrome. J Rheumatol 2002, 29:1342–1344.

    PubMed  Google Scholar 

  38. Steinfeld S, Cogan E, King LS, et al.: Abnormal distribution of aquaporin-5 water channel protein in salivary glands from Sjögren’s syndrome patients. Lab Invest 2001, 81:143–148.

    PubMed  CAS  Google Scholar 

  39. Tsubota K, Hirai S, King LS, et al.: Defective cellular trafficking of lacrimal gland aquaporin-5 in Sjögren’s syndrome. Lancet 2001, 357:688–689.

    Article  PubMed  CAS  Google Scholar 

  40. Beroukas D, Hiscock J, Jonsson R, et al.: Subcellular distribu-tion of aquaporin 5 in salivary glands in primary Sjögren’s syndrome. Lancet 2001, 358:1875–1876.

    Article  PubMed  CAS  Google Scholar 

  41. Beroukas D, Hiscock J, Gannon J, et al.: Selective down regula-tion of aquaporin-1 in salivary glands in primary Sjögren’s syndrome. Lab Invest 2002, 82:1547–1552. The aquaporin studies in SS have previously presented some conflict-ing results. In this paper, it is shown for the first time that maybe the most important change in the distribution of these proteins is related to aquaporin-1, which is downregulated. This may give some clues to the deranged physiology of the exocrine glands in SS.

    PubMed  CAS  Google Scholar 

  42. Dawson LJ, Field EA, Harmer AR, et al.: Acetylcholine -evoked calcium mobilization and ion channel activation in human labial gland acinar cells from patients with primary Sjögren’s syndrome. Clin Exp Immunol 2001, 124:480–485.

    Article  PubMed  CAS  Google Scholar 

  43. Konttinen YT, Käsnä-Ronkainen L: Sjögren’s syndrome: view-point on pathogenesis. Scand J Rheumatol Suppl 2002, 116:15–22.

    Article  PubMed  Google Scholar 

  44. Cutolo M, Wilder RL: Different roles for androgens and estro-gens in the susceptibility to autoimmune rheumatic diseases. Rheum Dis Clin North Am 2000, 6:825–839.

    Article  Google Scholar 

  45. Valtysdottir ST, Wide L, Hällgren R: Low serum dehydroepi- and rosterone sulfate in women with primary Sjögren’s syn-drome as an isolated sign of impaired HPA axis function. J Rheumatol 2001, 28:1259–1265.

    PubMed  CAS  Google Scholar 

  46. Lwin CTT, Bishay M, Platts RG, et al.: The assessment of fatigue in primary Sjögren’s syndrome. Scand J Rheumatol 2003, 32:33–37.

    Article  PubMed  Google Scholar 

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  1. Broegelmann Research Laboratory, The Gade Institute, University of Bergen, Armauer Hansen Building, NO-5021, Bergen, Norway

    Roland Jonsson DMD, PhD

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  2. Tom P. Gordon MD
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  3. Yrjö T. Konttinen MD
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Jonsson, R., Gordon, T.P. & Konttinen, Y.T. Recent advances in understanding molecular mechanisms in the pathogenesis and antibody profile of Sjögren’s syndrome. Curr Rheumatol Rep 5, 311–316 (2003). https://doi.org/10.1007/s11926-003-0010-z

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  • DOI: https://doi.org/10.1007/s11926-003-0010-z

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