Abstract
Sjogren's syndrome (SS) is a chronic autoimmune connective tissue disease. Varying rates of system involvements may be seen in the course of the disease. Semaphorins has multifunctions in several physiological and pathological processes such as immune system regulation. The association of Semaphorin 3A (Sema3A) and Semaphorin 7A (Sema7A), which are immune semaphorins, with autoimmune diseases is interesting for researchers. We aimed to compare serum Sema3A and Sema7A levels between primary SS and control subjects, and investigated Sema3A and Sema7A levels in disease subgroups and associated system involvements. 50 consecutive primary SS patients and 40 healthy subjects followed in the Rheumatology clinic of Cumhuriyet University Medical Faculty between 2017 and 2018 were included in the study. Inclusion criteria of patients were diagnosis of primary SS according to the 2016 ACR/EULAR classification criteria. Serum Sema3A and Sema7A levels were measured by commercial ELISA kit. Both groups were similar in terms of age, gender, and body mass index. Serum Sema3A and Sema7A levels were significantly lower in SS than in the controls (p = 0.001 and p = 0.005, respectively). Serum Sema3A levels were significantly lower in patients with renal involvement than in patients without (p = 0.03). Sema3A and Sema7A may play a role in the etiopathogenesis of SS and may be a potential serological marker for the diagnosis of SS and may be a target for treatment.
Similar content being viewed by others
Data availability
All data have been included into the manuscript.
References
Negrini S, Emmi G, Greco M et al (2022) Sjögren’s syndrome: a systemic autoimmune disease. Clin Exp Med 22:9–25. https://doi.org/10.1007/s10238-021-00728-6
Christodoulou MI, Kapsogeorgou EK, Moutsopoulos HM (2010) Characteristics of the minor salivary gland infiltrates in Sjögren’s syndrome. J Autoimmun 34:400–407. https://doi.org/10.1016/j.jaut.2009.10.004
Brito-Zeron P, Baldini C, Bootsma H et al (2016) Sjögren syndrome. Nat Rev Dis Prim 2:16047. https://doi.org/10.1038/nrdp.2016.47
Callegher SZ, Giovannini I, Zenz S et al (2022) Sjögren syndrome: looking forward to the future. Ther Adv Musculoskelet Dis. https://doi.org/10.1177/1759720X221100295
Ferro F, Vagelli R, Bruni C et al (2016) One year in review 2016: Sjögren’s syndrome. Clin Exp Rheumatol 34:161–171
Stojan G, Baer AN, Danoff SK (2013) Pulmonary manifestations of Sjögren’s syndrome. Curr Allergy Asthma Rep 13:354–360. https://doi.org/10.1007/s11882-013-0357-9
Tobn GJ, Pers JO, Devauchelle-Pensec V, Youinou P (2012) Neurological disorders in primary Sjögren’s syndrome. Autoimmune Dis 2012:645967. https://doi.org/10.1155/2012/645967
Baimpa E, Dahabreh IJ, Voulgarelis M, Moutsopoulos HM (2009) Hematologic manifestations and predictors of lymphoma development in primary Sjögren syndrome: clinical and pathophysiologic aspects. Medicine (Baltimore) 88:284–293. https://doi.org/10.1097/MD.0b013e3181b76ab5
Popov Y, Salomon-Escoto K (2018) Gastrointestinal and hepatic disease in Sjogren syndrome. Rheum Dis Clin North Am 44:143–151. https://doi.org/10.1016/j.rdc.2017.09.010
Baldini C, Pepe P, Quartuccio L et al (2014) Primary Sjogren’s syndrome as a multi-organ disease: impact of the serological profile on the clinical presentation of the disease in a large cohort of Italian patients. Rheumatology (Oxford) 53:839–844. https://doi.org/10.1093/rheumatology/ket427
Yazdani U, Terman JR (2006) The semaphorins. Genome Biol 7:211. https://doi.org/10.1186/gb-2006-7-3-211
Suzuki K, Kumanogoh A, Kikutani H (2008) Semaphorins and their receptors in immune cell interactions. Nat Immunol 9:17–23. https://doi.org/10.1038/ni1553
Lepelletier Y, Moura IC, Hadj-Slimane R et al (2006) Immunosuppressive role of semaphorin-3A on T cell proliferation is mediated by inhibition of actin cytoskeleton reorganization. Eur J Immunol 36:1782–1793. https://doi.org/10.1002/eji.200535601
Rezaeepoor M, Shapoori S, Ganjalikhani-hakemi M et al (2017) Decreased expression of Sema3A, an immune modulator, in blood sample of multiple sclerosis patients. Gene 610:59–63. https://doi.org/10.1016/j.gene.2017.02.013
Rimar D, Nov Y, Rosner I et al (2015) Semaphorin 3A: an immunoregulator in systemic sclerosis. Rheumatol Int 35:1625–1630. https://doi.org/10.1007/s00296-015-3269-2
Vadasz Z, Toubi E (2012) Semaphorin 3A – a marker for disease activity and a potential putative disease-modifying treatment in systemic lupus erythematosus. Lupus 21:1266–1270. https://doi.org/10.1177/0961203312456753
Vadasz Z, Haj T, Halasz K et al (2012) Semaphorin 3A is a marker for disease activity and a potential immunoregulator in systemic lupus erythematosus. Arthritis Res Ther 14:146
Takagawa S, Nakamura F, Kumagai K et al (2013) Decreased Semaphorin3A expression correlates with disease activity and histological features of rheumatoid arthritis. BMC Musculoskelet Disord 14:40
Liao HT, Lin YF, Chou CT, Tsai CY (2019) Semaphorin 3A in ankylosing spondylitis. J Microbiol Immunol Infect 52:151–157. https://doi.org/10.1016/j.jmii.2017.07.001
Suzuki K, Okuno T, Yamamoto M et al (2007) Semaphorin 7A initiates T-cell-mediated inflammatory responses through alpha1beta1 integrin. Nature 446:680–684. https://doi.org/10.1038/nature05652
Wang P, Mao YM, Liu LN et al (2020) Decreased expression of semaphorin 3A and semaphorin 7A levels and ıts association with systemic lupus erythematosus. Immunol Invest 49:69–80. https://doi.org/10.1080/08820139.2019.1649280
Shiboski CH, Shiboski SC, Seror R et al (2017) 2016 American college of rheumatology/European league against rheumatism classification criteria for primary Sjögren’s syndrome: a consensus and data-driven methodology ınvolving three ınternational patient cohorts. Arthritis Rheumatol 69:35–45. https://doi.org/10.1002/art.39859
Ramos-Casals M, Font J (2005) Primary Sjögren’s syndrome: current and emergent aetiopathogenic concepts. Rheumatology (Oxford) 44:1354–1367. https://doi.org/10.1093/rheumatology/keh714
Yoshida Y, Kang S, Morishima A et al (2013) AB0114 semaphorin3a and semaphorin4d in rheumatoid arthritis. Ann Rheum Dis 72:A820.2. https://doi.org/10.1136/annrheumdis-2013-eular.2437
Daoussis D, Melissaropoulos K, Sakellaropoulos G et al (2017) A multicenter, open-label, comparative study of B-cell depletion therapy with rituximab for systemic sclerosis-associated interstitial lung disease. Semin Arthritis Rheum 46:625–631. https://doi.org/10.1016/j.semarthrit.2016.10.003
Holmes S, Downs AM, Fosberry A et al (2002) Sema7A is a potent monocyte stimulator. Scand J Immunol 56:270–275. https://doi.org/10.1046/j.1365-3083.2002.01129.x
Xie J, Wang H (2017) Semaphorin 7A as a potential immune regulator and promising therapeutic target in rheumatoid arthritis. Arthritis Res Ther 19:10. https://doi.org/10.1186/s13075-016-1217-5
Aiyegbusi O, McGregor L, McGeoch L et al (2021) Renal disease in primary Sjögren’s syndrome. Rheumatol Ther 8:63–80. https://doi.org/10.1007/s40744-020-00264-x
Evans R, Zdebik A, Ciurtin C, Walsh SB (2015) Renal involvement in primary Sjögren’s syndrome. Rheumatol (United Kingdom) 54:1541–1548. https://doi.org/10.1093/rheumatology/kev223
Ramos-Casals M, Brito-Zeron P, Solans R et al (2014) Systemic involvement in primary Sjogren’s syndrome evaluated by the EULAR-SS disease activity index: analysis of 921 Spanish patients (GEAS-SS Registry). Rheumatology 53:321–331. https://doi.org/10.1093/rheumatology/ket349
Abrol E, Gonzalez-Pulido C, Praena-Fernandez JM, Isenberg DA (2014) A retrospective study of long-term outcomes in 152 patients with primary Sjogren’s syndrome: 25-year experience. Clin Med 14:157–164. https://doi.org/10.7861/clinmedicine.14-2-157
Funding
None.
Author information
Authors and Affiliations
Contributions
EU performed the design of the study, data collection and interpretation, and all statistical analysis and ACU contributed. HOD performed biochemical analyses of the study. AS checked the final version of the manuscript. All authors read and approved the final manuscript.
Corresponding author
Ethics declarations
Conflict of interest
There is no conflict of interest.
Ethical approval
The study approval was obtained from the ethics committee of Cumhuriyet University Medical Faculty (date: 11th July 2017, approval number: 2017-07/08).
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Urhan, E., Urhan, A.C., Dogan, H.O. et al. Assessment of semaphorin 3A and semaphorin 7A levels in primary Sjogren's syndrome. Rheumatol Int 43, 1087–1092 (2023). https://doi.org/10.1007/s00296-022-05197-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00296-022-05197-y