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Experimental Therapies in Sjögren’s Syndrome

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Sjögren’s Syndrome

Abstract

Sjögren’s syndrome (SjS) is an autoimmune inflammatory disorder of exocrine glands that has a particular predilection for the lacrimal and salivary glands. Dry mouth and dry eyes are frequently proffered as presenting symptoms [1, 2]. These are in many cases accompanied by several nonspecific symptoms, such as malaise and fatigue [3]. In addition, extraglandular manifestations such as purpura, polyneuropathy, and arthritis can be present even as presenting signs of the disease [2]. The occurrence of lymphomas is another important issue in SjS that requires timely diagnosis and treatment [4]. This enlarges the possibilities for therapies aimed to slow down, stop, or even reverse the further development of SjS. This chapter describes experimental therapies that are aimed at reducing disease activity or reversing the progression of SjS [5].

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References

  1. Kalk WW, Mansour K, Vissink A, et al. Oral and ocular manifestations in Sjögren’s syndrome. J Rheumatol. 2002;29:924–30.

    PubMed  Google Scholar 

  2. Fox RI. Sjögren’s syndrome. Lancet. 2005;366(9482):321–31.

    Article  PubMed  CAS  Google Scholar 

  3. Meijer JM, Meiners PM, Huddleston Slater JJ, et al. Health-related quality of life, employment and disability in patients with Sjögren’s syndrome. Rheumatology (Oxford). 2009;48:1077–82.

    Article  Google Scholar 

  4. Zintzaras E, Voulgarelis M, Moutsopoulos HM. The risk of lymphoma development in autoimmune diseases: a meta-analysis. Arch Intern Med. 2005;165:2337–44.

    Article  PubMed  Google Scholar 

  5. Vissink A, Bootsma H, Spijkervet FKL, Hu S, Wong DT, Kallenberg CGM. Current and future challenges in primary Sjögren’s syndrome. Curr Pharm Biotechnol Rev. 2010; (in press).

    Google Scholar 

  6. Mignogna MD, Fedele S, Lo RL, Lo ML, Wolff A. Sjögren’s syndrome: the diagnostic potential of early oral manifestations preceding hyposalivation/xerostomia. J Oral Pathol Med. 2005;34:1–6.

    Article  PubMed  CAS  Google Scholar 

  7. Kalk WW, Vissink A, Spijkervet FK, Bootsma H, Kallenberg CG, Nieuw-Amerongen AV. Sialometry and sialochemistry: diagnostic tools for Sjögren’s syndrome. Ann Rheum Dis. 2001;60:1110–6.

    Article  PubMed  CAS  Google Scholar 

  8. Higashi K, Yoshida M, Igarashi A, et al. Intense correlation between protein-conjugated acrolein and primary Sjögren’s syndrome. Clin Chim Acta. 2010;411(5–6):359–63.

    Article  PubMed  CAS  Google Scholar 

  9. 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;61:554–8.

    Article  PubMed  CAS  Google Scholar 

  10. Kalk WW, Vissink A, Stegenga B, Bootsma H, Nieuw Amerongen AV, Kallenberg CG. Sialometry and sialochemistry: a non-invasive approach for diagnosing Sjögren’s syndrome. Ann Rheum Dis. 2002;61:137–44.

    Article  PubMed  CAS  Google Scholar 

  11. Kalk WW, Vissink A, Spijkervet FK, Möller JM, Roodenburg JL. Morbidity from parotid sialography. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2001;92:572–5.

    Article  PubMed  CAS  Google Scholar 

  12. Pijpe J, Kalk WW, Bootsma H, Spijkervet FK, Kallenberg CG, Vissink A. Progression of salivary gland dysfunction in patients with Sjögren’s syndrome. Ann Rheum Dis. 2007;66:107–12.

    Article  PubMed  CAS  Google Scholar 

  13. Pedersen AM, Bardow A, Nauntofte B. Salivary changes and dental caries as potential oral markers of autoimmune salivary gland dysfunction in primary Sjögren’s syndrome. BMC Clin Pathol. 2005;5:4.

    Article  PubMed  Google Scholar 

  14. Pedersen AM, Reibel J, Nordgarden H, Bergem HO, Jensen JL, Nauntofte B. Primary Sjögren’s syndrome: salivary gland function and clinical oral findings. Oral Dis. 1999;5:128–38.

    Article  PubMed  CAS  Google Scholar 

  15. Pijpe J, van Imhoff GW, Spijkervet FK, et al. Rituximab treatment in patients with primary Sjögren’s syndrome: an open-label phase II study. Arthritis Rheum. 2005;52:2740–50.

    Article  PubMed  CAS  Google Scholar 

  16. Pijpe J, Meijer JM, Bootsma H, et al. Clinical and histologic evidence of salivary gland restoration supports the efficacy of rituximab treatment in Sjögren’s syndrome. Arthritis Rheum. 2009;60:3251–6.

    Article  PubMed  CAS  Google Scholar 

  17. Meijer JM, Meiners PM, Vissink A, et al. Effective rituximab treatment in primary Sjögren’s syndrome: a randomised, double-blind, placebo-controlled trial. Arthritis Rheum. 2010;62:960–8.

    Article  PubMed  CAS  Google Scholar 

  18. Meiners PM, Vissink A, Kallenberg CG, Kroese FG, Bootsma H. Treatment of primary Sjögren’s syndrome with anti-CD20 therapy (rituximab). A feasible approach or just a starting point? Expert Opin Biol Ther. 2011 Aug 7. [Epub ahead of print].

    Google Scholar 

  19. Pijpe J, Kalk WW, van der Wal JE, et al. Parotid gland biopsy compared with labial biopsy in the diagnosis of patients with primary Sjögren’s syndrome. Rheumatology (Oxford). 2007;46:335–41.

    Article  CAS  Google Scholar 

  20. Meijer JM, Pijpe J, Vissink A, Kallenberg CG, Bootsma H. Treatment of primary Sjögren syndrome with rituximab: extended follow-up, safety and efficacy of retreatment. Ann Rheum Dis. 2009;68:284–5.

    Article  PubMed  CAS  Google Scholar 

  21. Kourbeti IS, Boumpas DT. Biological therapies of autoimmune diseases. Curr Drug Targets Inflamm Allergy. 2005;4:41–6.

    Article  PubMed  CAS  Google Scholar 

  22. Meijer JM, Pijpe J, Bootsma H, Vissink A, Kallenberg CG. The future of biologic agents in the treatment of Sjögren’s syndrome. Clin Rev Allergy Immunol. 2007;32:292–7.

    Article  PubMed  CAS  Google Scholar 

  23. Roescher N, Tak PP, Illei GG. Cytokines in Sjögren’s syndrome. Oral Dis. 2009;15:519–26.

    Article  PubMed  CAS  Google Scholar 

  24. Roescher N, Tak PP, Illei GG. Cytokines in Sjögren’s syndrome: potential therapeutic targets. Ann Rheum Dis. 2010;69(6):945–8.

    Article  PubMed  CAS  Google Scholar 

  25. Tobón GJ, Saraux A, Pers JO, Youinou P. Emerging biotherapies for Sjögren’s syndrome. Expert Opin Emerg Drugs. 2010;5:269–82.

    Article  Google Scholar 

  26. d’Arbonneau F, Pers JO, Devauchelle V, Pennec Y, Saraux A, Youinou P. BAFF-induced changes in B cell antigen receptor-containing lipid rafts in Sjögren’s syndrome. Arthritis Rheum. 2006;54:115–26.

    Article  PubMed  Google Scholar 

  27. Båve U, Nordmark G, Lövgren T, et al. Activation of the type I interferon system in primary Sjögren’s syndrome: a possible etiopathogenic mechanism. Arthritis Rheum. 2005;52:1185–95.

    Article  PubMed  Google Scholar 

  28. Cummins MJ, Papas A, Kammer GM, Fox PC. Treatment of primary Sjögren’s syndrome with low-dose human interferon alfa administered by the oromucosal route: combined phase III results. Arthritis Rheum. 2003;49:585–93.

    Article  PubMed  CAS  Google Scholar 

  29. Shiozawa S, Tanaka Y, Shiozawa K. Single-blinded controlled trial of low-dose oral IFN-alpha for the treatment of xerostomia in patients with Sjögren’s syndrome. J Interferon Cytokine Res. 1998;18:255–62.

    Article  PubMed  CAS  Google Scholar 

  30. Ferraccioli GF, Salaffi F, De Vita S, et al. Interferon alpha-2 (IFN alpha 2) increases lacrimal and salivary function in Sjögren’s syndrome patients. Preliminary results of an open pilot trial versus OH-chloroquine. Clin Exp Rheumatol. 1996;14:367–71.

    PubMed  CAS  Google Scholar 

  31. Ship JA, Fox PC, Michalek JE, Cummins MJ, Richards AB. Treatment of primary Sjögren’s syndrome with low-dose natural human interferon-alpha administered by the oral mucosal route: a phase II clinical trial. J Interferon Cytokine Res. 1999;19:943–51.

    Article  PubMed  CAS  Google Scholar 

  32. Khurshudian AVA. A pilot study to test the efficacy of oral administration of interferon-alpha lozenges to patients with Sjögren’s syndrome. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2003;95:38–44.

    Article  PubMed  Google Scholar 

  33. Willeke P, Schlüter B, Schotte H, Domschke W, Gaubitz M, Becker H. Interferon-gamma is increased in patients with primary Sjögren’s syndrome and Raynaud’s phenomenon. Semin Arthritis Rheum. 2009;39:197–202.

    Article  PubMed  CAS  Google Scholar 

  34. Oxholm P, Daniels TE, Bendtzen K. Cytokine expression in labial salivary glands from patients with primary Sjögren’s syndrome. Autoimmunity. 1992;12:185–91.

    Article  PubMed  CAS  Google Scholar 

  35. Wu AJ, Kurrasch RH, Katz J, Fox PC, Baum BJ, Atkinson JC. Effect of tumor necrosis factor-alpha and interferon-gamma on the growth of a human salivary gland cell line. J Cell Physiol. 1994;161:217–26.

    Article  PubMed  CAS  Google Scholar 

  36. Daniels PJ, Gustafson SA, French D, Wang Y, DePond W, McArthur CP. Interferon-mediated block in cell cycle and altered integrin expression in a differentiated salivary gland cell line (HSG) cultured on Matrigel. J Interferon Cytokine Res. 2000;20:1101–9.

    Article  PubMed  CAS  Google Scholar 

  37. Smolen JS, Beaulieu A, Rubbert-Roth A, OPTION Investigators, et al. Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial. Lancet. 2008;371(9617):987–97.

    Article  PubMed  CAS  Google Scholar 

  38. Illei GG, Shirota Y, Yarboro CH, et al. Tocilizumab in systemic lupus erythematosus: data on safety, preliminary efficacy, and impact on circulating plasma cells from an open-label phase I dosage-escalation study. Arthritis Rheum. 2010;62:542–52.

    Article  PubMed  CAS  Google Scholar 

  39. Bikker A, van Woerkom JM, Kruize AA, et al. Increased expression of interleukin-7 in labial salivary glands of patients with primary Sjögren’s syndrome correlates with increased inflammation. Arthritis Rheum. 2010;62:969–77.

    Article  PubMed  CAS  Google Scholar 

  40. Tak PP, Bacchi M, Bertolino M. Pharmacokinetics of IL-18 binding protein in healthy volunteers and subjects with rheumatoid arthritis or plaque psoriasis. Eur J Drug Metab Pharmacokinet. 2006;31:109–16.

    Article  PubMed  CAS  Google Scholar 

  41. Ding C, Xu J, Li J. ABT-874, a fully human monoclonal anti-IL-12/IL-23 antibody for the potential treatment of autoimmune diseases. Curr Opin Investig Drugs. 2008;9:515–22.

    PubMed  CAS  Google Scholar 

  42. Oppmann B, Lesley R, Blom B, et al. Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity. 2000;13:715–25.

    Article  PubMed  CAS  Google Scholar 

  43. Kikly K, Liu L, Na S, Sedgwick JD. The IL-23/Th(17) axis: therapeutic targets for ­autoimmune inflammation. Curr Opin Immunol. 2006;8:670–5.

    Article  Google Scholar 

  44. Katsifis GE, Rekka S, Moutsopoulos NM, Pillemer S, Wahl SM. Systemic and local ­interleukin-17 and linked cytokines associated with Sjögren’s syndrome immunopathogenesis. Am J Pathol. 2009;175:1167–77.

    Article  PubMed  CAS  Google Scholar 

  45. Nguyen CQ, Hu MH, Li Y, Stewart C, Peck AB. Salivary gland tissue expression of interleukin-23 and interleukin-17 in Sjögren’s syndrome: findings in humans and mice. Arthritis Rheum. 2008;58:734–43.

    Article  PubMed  CAS  Google Scholar 

  46. Sakai A, Sugawara Y, Kuroishi T, Sasano T, Sugawara S. Identification of IL-18 and Th17 cells in salivary glands of patients with Sjögren’s syndrome, and amplification of IL-17-mediated secretion of inflammatory cytokines from salivary gland cells by IL-18. J Immunol. 2008;181:2898–906.

    PubMed  CAS  Google Scholar 

  47. Kok MR, Baum BJ, Tak PP, Pillemer SR. Use of localised gene transfer to develop new treatment strategies for the salivary component of Sjögren’s syndrome. Ann Rheum Dis. 2003;62:1038–46.

    Article  PubMed  CAS  Google Scholar 

  48. Lodde BM, Baum BJ, Tak PP, Illei G. Experience with experimental biological treatment and local gene therapy in Sjögren’s syndrome: implications for exocrine pathogenesis and treatment. Ann Rheum Dis. 2006;65:1406–13.

    Article  PubMed  CAS  Google Scholar 

  49. Le Pottier L, Bendaoud B, Renaudineau Y, Youinou P, Pers JO, Daridon C. New ELISA for B cell-activating factor. Clin Chem. 2009;55:1843–51.

    Article  PubMed  Google Scholar 

  50. Pers JO, d’Arbonneau F, Devauchelle-Pensec V, Saraux A, Pennec YL, Youinou P. Is periodontal disease mediated by salivary BAFF in Sjögren’s syndrome? Arthritis Rheum. 2005;52:2411–4.

    Article  PubMed  Google Scholar 

  51. Szodoray P, Jellestad S, Alex P, et al. Programmed cell death of peripheral blood B cells determined by laser scanning cytometry in Sjögren’s syndrome with a special emphasis on BAFF. J Clin Immunol. 2004;24:600–11.

    Article  PubMed  Google Scholar 

  52. Baker KP, Edwards BM, Main SH, et al. Generation and characterization of LymphoStat-B, a human monoclonal antibody that antagonizes the bioactivities of B lymphocyte stimulator. Arthritis Rheum. 2003;48:3253–65.

    Article  PubMed  CAS  Google Scholar 

  53. Ramanujam M, Davidson A. The current status of targeting BAFF/BLyS for autoimmune diseases. Arthritis Res Ther. 2004;6:197–202.

    Article  PubMed  CAS  Google Scholar 

  54. Szodoray P, Jonsson R. The BAFF/APRIL system in systemic autoimmune diseases with a special emphasis on Sjögren’s syndrome. Scand J Immunol. 2005;62:421–8.

    Article  PubMed  CAS  Google Scholar 

  55. Jacobi AM, Huang W, Wang T, et al. Effect of long-term belimumab treatment on B cells in systemic lupus erythematosus: extension of a phase II, double-blind, placebo-controlled, dose-ranging study. Arthritis Rheum. 2010;62(1):201–10.

    Article  PubMed  CAS  Google Scholar 

  56. Navarra SV, Guzman RM, Gallacher AE, BLISS-52 Study Group. Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial. Lancet. 2011;377(9767):721–31. doi:10.1016/S0140-6736(10)61354-62. Published online Feb 7.

    Article  PubMed  CAS  Google Scholar 

  57. Stone JH. BLISS! Lupus learns its lessons. Lancet. 2011;377(9767):693–4. Published online Feb 7.

    Article  PubMed  Google Scholar 

  58. Seror R, Sordet C, Guillevin L, et al. Tolerance and efficacy of rituximab and changes in serum B cell biomarkers in patients with systemic complications of primary Sjögren’s syndrome. Ann Rheum Dis. 2007;66:351–7.

    Article  PubMed  CAS  Google Scholar 

  59. Gottenberg JE, Guillevin L, Lambotte O, et al. Tolerance and short term efficacy of rituximab in 43 patients with systemic autoimmune diseases. Ann Rheum Dis. 2005;64(6):913–20.

    Article  PubMed  CAS  Google Scholar 

  60. Devauchelle-Pensec V, Pennec Y, Morvan J, et al. Improvement of Sjögren’s syndrome after two infusions of rituximab (anti-CD20). Arthritis Rheum. 2007;57:310–7.

    Article  PubMed  CAS  Google Scholar 

  61. Dass S, Bowman SJ, Vital EM, Ikeda K, Pease CT, Hamburger J, et al. Reduction of fatigue in Sjögren syndrome with rituximab: results of a randomised, double-blind, placebo-controlled pilot study. Ann Rheum Dis. 2008;67(11):1541–4.

    Article  PubMed  CAS  Google Scholar 

  62. Pers JO, Devauchelle V, Daridon C, et al. BAFF-modulated repopulation of B lymphocytes in the blood and salivary glands of rituximab-treated patients with Sjögren’s syndrome. Arthritis Rheum. 2007;56:1464–77.

    Article  PubMed  Google Scholar 

  63. Daridon C, Devauchelle V, Hutin P, et al. Aberrant expression of BAFF by B lymphocytes infiltrating the salivary glands of patients with primary Sjögren’s syndrome. Arthritis Rheum. 2007;56:1134–44.

    Article  PubMed  CAS  Google Scholar 

  64. Carnahan J, Wang P, Kendall R, et al. Epratuzumab, a humanized monoclonal antibody targeting CD22: characterization of in vitro properties. Clin Cancer Res. 2003;9(10 Pt 2):3982S–90S.

    PubMed  CAS  Google Scholar 

  65. Steinfeld SD, Tant L, Burmester GR, et al. Epratuzumab (humanized anti-CD22 antibody) in primary Sjögren’s syndrome: an open-label Phase I/II study. Arthritis Res Ther. 2006;8:R129.

    Article  PubMed  Google Scholar 

  66. Genovese MC, Schiff M, Luggen M, et al. Efficacy and safety of the selective co-stimulation modulator abatacept following 2 years of treatment in patients with rheumatoid arthritis and an inadequate response to anti-tumour necrosis factor therapy. Ann Rheum Dis. 2008;67:547–54.

    Article  PubMed  CAS  Google Scholar 

  67. Choy EH. Selective modulation of T cell co-stimulation: a novel mode of action for the treatment of rheumatoid arthritis. Clin Exp Rheumatol. 2009;27(3):510–8.

    PubMed  CAS  Google Scholar 

  68. Kagami H, Wang S, Hai B. Restoring the function of salivary glands. Oral Dis. 2008;14:15–24.

    PubMed  CAS  Google Scholar 

  69. Kok MR, Yamano S, Lodde BM, et al. Local adeno-associated virus-mediated interleukin 10 gene transfer has disease-modifying effects in a murine model of Sjögren’s syndrome. Hum Gene Ther. 2003;14:1605–18.

    Article  PubMed  CAS  Google Scholar 

  70. Lodde BM, Mineshiba F, Wang J, et al. Effect of human vasoactive intestinal peptide gene transfer in a murine model of Sjögren’s syndrome. Ann Rheum Dis. 2006;65:195–200.

    Article  PubMed  CAS  Google Scholar 

  71. Vosters JL, Yin H, Roescher N, Kok MR, Tak PP, Chiorini JA. Local expression of tumor necrosis factor-receptor 1: immunoglobulin G can induce salivary gland dysfunction in a murine model of Sjögren’s syndrome. Arthritis Res Ther. 2009;11:R189.

    Article  PubMed  Google Scholar 

  72. Coppes RP, Stokman MA. Stem cells and the repair of radiation-induced salivary gland damage. Oral Dis. 2010;17(2):143–53.

    Article  PubMed  Google Scholar 

  73. Lombaert IM, Brunsting JF, Wierenga PK, et al. Rescue of salivary gland function after stem cell transplantation in irradiated glands. PLoS One. 2008;3:e2063.

    Article  PubMed  Google Scholar 

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Vissink, A., Bootsma, H., Spijkervet, F.K.L., Kallenberg, C.G.M. (2011). Experimental Therapies in Sjögren’s Syndrome. In: Ramos-Casals, M., Stone, J., Moutsopoulos, H. (eds) Sjögren’s Syndrome. Springer, London. https://doi.org/10.1007/978-0-85729-947-5_42

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