Primer Sjögren Sendromunda Ekstra-glandüler Bulguların Oto-antikorlarla İlişkisi

Öz

Primer Sjögren sendromunda (pSS) serumdaki oto-antikorların varlığı hem daha şiddetli glandüler tutulum hem de daha fazla extra-glandüler bulgu prevalansı ile ilişkilendirilmektedir. Bu çalışmanın amacı pSS hastalarındaki extra-glandüler bulguların sıklığının saptanması ve oto-antikorların varlığı ve sayısı ile ilişkisinin belirlenmesidir. Bu retrospektif kesitsel çalışmaya 2018-2023 tarihleri arasında Mersin Üniversitesi Tıp Fakültesi Hastanesi Romatoloji polikliniğinde pSS tanısı ile takip edilmiş olan 209 hasta dahil edildi. Hastaların demografik ve klinik verileri, extra-glandüler bulguları ve serum oto-antikor profili analiz edildi. Hastaların 92’sinde (%44) ekstra-glandüler bulgu mevcuttu. En sık olarak artrit görülürken, bunu interstisyel akciğer hastalığı takip etmekteydi. Erkeklerde ekstra-glandüler tutulum sıklığı kadınlardan daha fazla bulundu (p=0.050). Anti-SSB pozitifliği olanlarda interstisyel akciğer hastalığı (İAH) ve polinöropati (PNP) daha sık saptanmıştır (sırasıyla p=0.002, p=0.050). RF pozitifliği olanlarda ise artrit ve lenfomanın daha sık görüldüğü gözlenmiştir (sırasıyla p=0.031, p=0.011). Tüm oto-antikorları negatif hastalarda extra-glandüler tutulum daha az saptandı (p=0.005). Anti-SSA ve SSB’nin birlikte pozitif olduğu hastalarda İAH ve PNP daha sıktı (p=0.004 ve p=0.043, sırasıyla). pSS’unda hastaların yaklaşık yarısında extra-glandüler bulgular eşlik etmekte olup, otoantikor oluşumu ve bunların birlikte pozitifliği daha fazla sistemik tutuluma neden olmaktadır. Anti-SSB antikor pozitifliği PNP ve İAH gelişimi riski ile ilişkili iken RF pozitifliği ise artrit ve lenfoma riski ile ilişkilidir.

Anahtar Kelimeler

• Anti-SSA
• Anti-SSB
• Extra-glandüler bulgular
• Otoantikor
• Primer Sjögren sendromu

Relationship between Extra-glandular Manifestations and Auto-antibodies in Primary Sjögren's Syndrome

Öz

The presence of serum autoantibodies in primary Sjögren's syndrome (pSS) is associated with more severe glandular disease and a higher incidence of extra-glandular manifestations. This study aims to establish the prevalence of extra glandular symptoms in patients with pSS and their relationship to the existence and number of autoantibodies. This retrospective cross-sectional study comprised 209 patients diagnosed with pSS in the Rheumatology outpatient clinic at Mersin University Faculty of Medicine Hospital between 2018 and 2023. The patient's demographic and clinical data, extra glandular manifestations, and serum autoantibody profiles were analyzed. Extra glandular symptoms were identified in 92 patients (44%). The most common manifestation was arthritis, followed by interstitial lung disease (ILD). Extra-glandular involvement was found to be more common in men than in women (p=0.050). Extra glandular involvement was less prevalent in patients who were negative for all autoantibodies (p=0.005). Patients who were positive for Anti-SSB had higher frequencies of interstitial lung disease (ILD) and polyneuropathy (PNP) (p=0.002 and p=0.050, respectively). Additionally, those who were positive for rheumatoid factor (RF) showed a higher prevalence of arthritis and lymphoma (p=0.031 and p=0.011, respectively). Patients who were seropositive for both anti-SSA and anti-SSB also had a greater risk of interstitial lung disease (ILD) and polyneuropathy (PNP) (p=0.004 and p=0.043, respectively). Approximately half of pSS patients have extra glandular symptoms, and the production of autoantibodies and their concomitant positivity result in increasing systemic involvement. Anti-SSB antibody positivity increases the likelihood of developing PNP and ILD, whereas RF positivity increases the risk of developing arthritis and lymphoma.

Anahtar Kelimeler

• Anti-SSA
• Anti-SSB
• Extra-glandular manifestations
• Autoantibody
• Primary Sjögren

Kaynakça

1. 1. Mavragani CP, Moutsopoulos HM. The geoepidemiology of Sjögren's syndrome. Autoimmun Rev 2010;9(5):A305-10.
2. 2. Flores-Chávez A, Kostov B, Solans R, et al. Severe, life-threatening phenotype of primary Sjögren's syndrome: clinical characterization and outcomes in 1580 patients (GEAS-SS Registry). Clin Exp Rheumatol 2018;36 Suppl 112(3):121-9.
3. 3. 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(6):554-8.
4. 4. Routsias JG, Tzioufas AG. Sjogren’s syndrome study of autoantigens and autoantibodies. Clin Rev Allergy Immunol 2007;32(3):238-51.
5. 5. Bournia VK, Vlachoyiannopoulos PG. Subgroups of Sjögren syndrome patients according to serological profiles. J Autoimmun 2012;39(1-2):15-26.
6. 6. ter Borg EJ, Risselada AP, Kelder JC. Relation of systemic autoantibodies to the number of extra glandular manifestations in primary Sjögren's Syndrome: a retrospective analysis of 65 patients in the Netherlands. Semin Arthritis Rheum 2011;40(6):547-51.
7. 7. Singh AG, Singh S, Matteson EL. Rate, risk factors and causes of mortality in patients with Sjögren's syndrome: a systematic review and meta-analysis of cohort studies. Rheumatology (Oxford) 2016;55(3):450-60.
8. 8. Shiboski SC, Shiboski CH, Criswell L, et al. 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(4):475-87.

9. 9. Shiboski CH, Shiboski SC, Seror R, et al. 2016 American College of Rheumatology/European League Against Rheumatism classification criteria for primary Sjögren's syndrome: A consensus and data-driven methodology involving three international patient cohorts. Ann Rheum Dis 2017;76(1):9-16.
10. 10. Jorkjend L, Johansson A, Johansson AK. Prevalence of Extraglandular Manifestations in Patients With Primary Sjögren’s Syndrome in Southern Norway: A Comparison to the Literature. Arch Rheumatol 2015;30(3):263-70.
11. 11. Zhang Y, Li M, Zhang L, et al. Association between comorbidities and extra glandular manifestations in primary Sjögren's syndrome: a multicenter cross-sectional study. Clin Rheumatol 2020;39(9):2677-88.
12. 12. Scofield RH, Fayyaz A, Kurien BT, Koelsch KA. Prognostic value of Sjögren's syndrome autoantibodies. J Lab Precis Med 2018;3:10.21037/jlpm.2018.08.05.
13. 13. Nakamura H, Kawakami A, Eguchi K. Mechanisms of autoantibody production and the relationship between autoantibodies and the clinical manifestations in Sjögren's syndrome. Transl Res 2006;148(6):281-8.
14. 14. Tzioufas AG, Wassmuth R, Dafni UG, et al. Clinical, immunological, and immunogenetic aspects of autoantibody production against Ro/SSA, La/SSB and their linear epitopes in primary Sjögren's syndrome (pSS): a European multicentre study. Ann Rheum Dis 2002;61(5):398-404.
15. 15. Toker E, Yavuz S, Direskeneli H. Anti-Ro/SSA and anti-La/SSB autoantibodies in the tear fluid of patients with Sjögren's syndrome. Br J Ophthalmol 2004;88(3):384-7.
16. 16. Routsias JG, Tzioufas AG. Sjögren's syndrome–study of autoantigens and autoantibodies. Clin Rev Allergy Immunol 2007;32:238–51.
17. 17. Papageorgiou A, Voulgarelis M, Tzioufas AG. Clinical picture, outcome and predictive factors of lymphoma in Sjogren syndrome. Autoimmun Rev 2015;14:641–9.
18. 18. Fragkioudaki S, Mavragani CP, Moutsopoulos HM. Predicting the risk for lymphoma development in Sjogren syndrome: An easy tool for clinical use. Medicine (Baltimore) 2016;95:e3766.
19. 19. Ramírez Sepúlveda JI, Kvarnström M, Brauner S, Baldini C, Wahren-Herlenius M. Difference in clinical presentation between women and men in incident primary Sjögren's syndrome. Biol Sex Differ 2017;8:16.
20. 20. Ramírez Sepúlveda JI, Kvarnström M, Eriksson P, et al. Long-term follow-up in primary Sjögren's syndrome reveals differences in clinical presentation between female and male patients. Biol Sex Differ 2017;8(1):25.