J Rheum Dis.  2015 Jun;22(3):146-153. 10.4078/jrd.2015.22.3.146.

Update of Sjogren's Syndrome

• Jung JY
• Suh CH

• KMID: 2222880
• DOI: http://doi.org/10.4078/jrd.2015.22.3.146

Abstract

We reviewed the recent findings in diagnosis, pathogenesis and management of Sjogren's syndrome. New diagnostic classification criteria for Sjogren's syndrome were published by the American College of Rheumatology in 2012, and validation was completed. Salivary gland ultrasonography has been examined as a diagnostic and prognostic marker for Sjogren's syndrome, and the results have revealed that it has high specificity and low sensitivity. Disease activity assessment tools for Sjogren's syndrome have been developed and validated for upcoming clinical trials. Several associated genes were identified by genome-wide association studies, with large cohorts in Europe and China. Several single nucleotide polymorphisms of Sjogren's syndrome are related to germinal center formation and lymphoma development. New treatment modalities, including interleukin-1 receptor antagonist, anti-CD20, anti-BAFF/Blys, and CTLA4-immunoglobulin were investigated, but the optimal therapeutic compounds have yet to be found.

Keyword

Sjogren's Syndrome; Classification; Ultrasonography; Genes; Therapy

MeSH Terms

China
Classification
Cohort Studies
Diagnosis
Europe
Genome-Wide Association Study
Germinal Center
Interleukin-1
Lymphoma
Polymorphism, Single Nucleotide
Rheumatology
Salivary Glands
Sensitivity and Specificity
Sjogren's Syndrome*
Ultrasonography
Interleukin-1

Reference

1. Patel R, Shahane A. The epidemiology of Sjögren's syndrome. Clin Epidemiol. 2014; 6:247–55.

2. Liang Y, Yang Z, Qin B, Zhong R. Primary Sjögren's syndrome and malignancy risk: a systematic review and meta-analysis. Ann Rheum Dis. 2014; 73:1151–6.

3. Nordmark G, Kristjansdottir G, Theander E, Eriksson P, Brun JG, Wang C, et al. Additive effects of the major risk alleles of IRF5 and STAT4 in primary Sjögren's syndrome. Genes Immun. 2009; 10:68–76.

4. Mariette X, Roux S, Zhang J, Bengoufa D, Lavie F, Zhou T, et al. The level of BLyS (BAFF) correlates with the titre of autoantibodies in human Sjögren's syndrome. Ann Rheum Dis. 2003; 62:168–71.

5. Roescher N, Tak PP, Illei GG. Cytokines in Sjögren's syndrome: potential therapeutic targets. Ann Rheum Dis. 2010; 69:945–8.

6. Nocturne G, Mariette X. Advances in understanding the pathogenesis of primary Sjögren's syndrome. Nat Rev Rheumatol. 2013; 9:544–56.

7. Vitali C, Bombardieri S, Jonsson R, Moutsopoulos HM, Alexander EL, Carsons SE, et al. European Study Group on Classification Criteria for Sjögren's Syndrome. 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.

8. Sankar V, Noll JL, Brennan MT. Diagnosis of Sjögren's syndrome: American-European and the American College of Rheumatology classification criteria. Oral Maxillofac Surg Clin North Am. 2014; 26:13–22.

9. Shiboski SC, Shiboski CH, Criswell L, Baer A, Challacombe S, Lanfranchi H, et al. Sjögren's International Collaborative Clinical Alliance (SICCA) Research Groups. American College of Rheumatology classification criteria for Sjögren's syndrome: a data-driven, expert consensus approach in the Sjögren's International Collaborative Clinical Alliance cohort. Arthritis Care Res (Hoboken). 2012; 64:475–87.

10. Rasmussen A, Ice JA, Li H, Grundahl K, Kelly JA, Radfar L, et al. Comparison of the American-European Consensus Group Sjögren's syndrome classification criteria to newly proposed American College of Rheumatology criteria in a large, carefully characterised sicca cohort. Ann Rheum Dis. 2014; 73:31–8.

11. Lee YH, Song GG. A meta-analysis of the diagnostic value of minor salivary gland biopsy for primary Sjögren's syndrome. J Rheum Dis. 2014; 21:303–10.

12. Wernicke D, Hess H, Gromnica-Ihle E, Krause A, Schmidt WA. Ultrasonography of salivary glands: a highly specific imaging procedure for diagnosis of Sjögren's syndrome. J Rheumatol. 2008; 35:285–93.

13. Takagi Y, Kimura Y, Nakamura H, Sasaki M, Eguchi K, Nakamura T. Salivary gland ultrasonography: can it be an alternative to sialography as an imaging modality for Sjögren's syndrome? Ann Rheum Dis. 2010; 69:1321–4.

14. Cornec D, Jousse-Joulin S, Pers JO, Marhadour T, Cochener B, Boisramé-Gastrin S, et al. Contribution of salivary gland ultrasonography to the diagnosis of Sjögren's syndrome: toward new diagnostic criteria? Arthritis Rheum. 2013; 65:216–25.

15. Obinata K, Sato T, Ohmori K, Shindo M, Nakamura M. A comparison of diagnostic tools for Sjögren syndrome, with emphasis on sialography, histopathology, and ultrasonography. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010; 109:129–34.

16. Theander E, Mandl T. Primary Sjögren's syndrome: diagnostic and prognostic value of salivary gland ultrasonography using a simplified scoring system. Arthritis Care Res (Hoboken). 2014; 66:1102–7.

17. Goules AV, Tzioufas AG. Imaging: diagnostic value of ultrasonography in Sjögren's syndrome. Nat Rev Rheumatol. 2014; 10:450–2.

18. Cornec D, Jousse-Joulin S, Saraux A, Devauchelle-Pensec V. Salivary gland ultrasound to diagnose Sjögren's syndrome: a claim to standardize the procedure. Rheumatology (Oxford). 2015; 54:199–200.

19. Deng C, Hu C, Chen S, Li J, Wen X, Wu Z, et al. Meta-analysis of anti-muscarinic receptor type 3 antibodies for the diagnosis of Sjögren syndrome. PLoS One. 2015; 10:e0116744.

20. Delaleu N, Mydel P, Kwee I, Brun JG, Jonsson MV, Jonsson R. High fidelity between saliva proteomics and the biologic state of salivary glands defines biomarker signatures for primary Sjögren's syndrome. Arthritis Rheumatol. 2015; 67:1084–95.

21. Tzioufas AG, Kapsogeorgou EK. Biomarkers. Saliva proteomics is a promising tool to study Sjögren syndrome. Nat Rev Rheumatol. 2015; 11:202–3.

22. Seror R, Bootsma H, Bowman SJ, Dörner T, Gottenberg JE, Mariette X, et al. Outcome measures for primary Sjögren's syndrome. J Autoimmun. 2012; 39:97–102.

23. Seror R, Ravaud P, Bowman SJ, Baron G, Tzioufas A, Theander E, et al. EULAR Sjögren's Task Force. EULAR Sjögren's syndrome disease activity index: development of a consensus systemic disease activity index for primary Sjögren's syndrome. Ann Rheum Dis. 2010; 69:1103–9.

24. Seror R, Ravaud P, Mariette X, Bootsma H, Theander E, Hansen A, et al. EULAR Sjögren's Task Force. EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI): development of a consensus patient index for primary Sjogren's syndrome. Ann Rheum Dis. 2011; 70:968–72.

25. Seror R, Theander E, Brun JG, Ramos-Casals M, Valim V, Dörner T, et al. EULAR Sjögren's Task Force. Validation of EULAR primary Sjögren's syndrome disease activity (ESSDAI) and patient indexes (ESSPRI). Ann Rheum Dis. 2015; 74:859–66.

26. Seror R, Bootsma H, Saraux A, Bowman SJ, Theander E, Brun JG, et al. on behalf of the EULAR Sjögren's Task Force. Defining disease activity states and clinically meaningful improvement in primary Sjögren's syndrome with EULAR primary Sjögren's syndrome disease activity (ESSDAI) and patient-reported indexes (ESSPRI). Ann Rheum Dis. 2014; Dec 5 [Epub].DOI: DOI: 10.1136/annrheum-dis-2014-206008.

27. Burbelo PD, Ambatipudi K, Alevizos I. Genomewide association studies in Sjögren's syndrome: What do the genes tell us about disease pathogenesis? Autoimmun Rev. 2014; 13:756–61.

28. Nordmark G, Kristjansdottir G, Theander E, Appel S, Eriksson P, Vasaitis L, et al. Association of EBF1, FAM167A(C8orf13)-BLK and TNFSF4 gene variants with primary Sjögren's syndrome. Genes Immun. 2011; 12:100–9.

29. Li Y, Zhang K, Chen H, Sun F, Xu J, Wu Z, et al. A genomewide association study in Han Chinese identifies a susceptibility locus for primary Sjögren's syndrome at 7q11.23. Nat Genet. 2013; 45:1361–5.

30. Lessard CJ, Li H, Adrianto I, Ice JA, Rasmussen A, Grundahl KM, et al. Variants at multiple loci implicated in both innate and adaptive immune responses are associated with Sjögren's syndrome. Nat Genet. 2013; 45:1284–92.

31. Reksten TR, Johnsen SJ, Jonsson MV, Omdal R, Brun JG, Theander E, et al. Genetic associations to germinal centre formation in primary Sjögren's syndrome. Ann Rheum Dis. 2014; 73:1253–8.

32. Nocturne G, Boudaoud S, Miceli-Richard C, Viengchareun S, Lazure T, Nititham J, et al. Germline and somatic genetic variations of TNFAIP3 in lymphoma complicating primary Sjögren's syndrome. Blood. 2013; 122:4068–76.

33. Jonsson R, Theander E, Sjöström B, Brokstad K, Henriksson G. Autoantibodies present before symptom onset in primary Sjögren syndrome. JAMA. 2013; 6(310):1854–5.

34. Kwok SK, Lee J, Yu D, Kang KY, Cho M, Kim HR, et al. A pathogenetic role for IL-21 in primary Sjögren syndrome. Nat Rev Rheumatol. 2015; 11:368–74.

35. Kang KY, Kim HO, Kwok SK, Ju JH, Park KS, Sun DI, et al. Impact of interleukin-21 in the pathogenesis of primary Sjögren's syndrome: increased serum levels of interleukin-21 and its expression in the labial salivary glands. Arthritis Res Ther. 2011; 13:R179.

36. Liu H, Liu G, Gong L, Zhang Y, Jiang G. Local suppression of IL-21 in submandibular glands retards the development of Sjögren's syndrome in non-obese diabetic mice. J Oral Pathol Med. 2012; 41:728–35.

37. Mavragani CP, Schini M, Gravani F, Kaltsas G, Moutsopoulos HM. Brief report: adrenal autoimmunity in primary Sjögren's syndrome. Arthritis Rheum. 2012; 64:4066–71.

38. Gottenberg JE, Ravaud P, Puéchal X, Le Guern V, Sibilia J, Goeb V, et al. Effects of hydroxychloroquine on symptomatic improvement in primary Sjögren syndrome: the JOQUER randomized clinical trial. JAMA. 2014; 312:249–58.

39. Sada PR, Isenberg D, Ciurtin C. Biologic treatment in Sjögren's syndrome. Rheumatology (Oxford). 2015; 54:219–30.

40. Jousse-Joulin S, Devauchelle-Pensec V, Cornec D, Marhadour T, Bressollette L, Gestin S, et al. Brief report: ultrasonographic assessment of salivary gland response to rituximab in primary Sjögren's syndrome. Arthritis Rheumatol. 2015; 67:1623–8.

41. Mariette X, Seror R, Quartuccio L, Baron G, Salvin S, Fabris M, et al. Efficacy and safety of belimumab in primary Sjögren's syndrome: results of the BELISS open-label phase II study. Ann Rheum Dis. 2015; 74:526–31.

42. Meiners PM, Vissink A, Kroese FG, Spijkervet FK, Smitt-Kamminga NS, Abdulahad WH, et al. Abatacept treatment reduces disease activity in early primary Sjögren's syndrome (open-label proof of concept ASAP study). Ann Rheum Dis. 2014; 73:1393–6.

43. ClinicalTraials.gov. A service of the U.S. National Institutes of Health [Internet]. Bethesda (MD): the NIH National Library of Medicine;c2015. [cited 2015 May 7]. Avaliable from:. http://clinicaltrials.gov.