THE POSSIBLE RELATIONSHIPS BETWEEN SOME GENE POLYMORPHISMS AND SJOGREN’S SYNDROME

Yıl 2023, Cilt: 47 Sayı: 3, 1141 - 1154, 20.09.2023

Ülkü Terzi , İlker Ateş

https://doi.org/10.33483/jfpau.1328811

Öz

Objective: Sjögren’s syndrome is a complex and widespread autoimmune disease whose pathogenesis is not fully elucidated and environmental and genetic factors affect the development of the disease. In order to reveal the effect of genetic contribution, studies have been conducted on the genes previously shown to play a role in other autoimmune diseases such as systemic lupus erythromatosus. In addition, two GWAS studies were conducted to investigate the role of more genes in the disease by screening the entire genome and the relationship of previously unknown genes with SS was shown.
Result and Discussion: Studies are being conducted with spontaneous and genetically modified animal models in order to better reveal the relationship between SS and genes and to reinforce the data obtained from humans. In this study, the relationship between the genes previously studied in other autoimmune diseases and the genes associated with SS in GWAS studies and the possible pathways that may contribute to the pathogenesis of the disease through related genes were investigated.

Anahtar Kelimeler

Autoiımmune disease, gene polymorphisms, genetic toxic effects, genotoxicity, Sjögren’s syndrome

SJÖGREN SENDROMU İLE BAZI GEN POLİMORFİZMLERİ ARASINDAKİ OLASI BAĞLANTILAR

Öz

Amaç: Sjögren sendromu hala patogenezisi tam olarak aydınlatılamamış, hastalık gelişimini çevresel ve genetik faktörlerin etkilediği kompleks ve yaygın bir otoimmün hastalıktır. Genetik katkının etkisini ortaya koymak için daha önce sistemik lupus eritromatozus gibi diğer otoimmün hastalıklarda rolü gösterilen genler üzerinde bu genlerin SS ile ilişkisini ortaya koymak için çalışmalar yapılmıştır. Ayrıca iki GWAS çalışmasıyla da tüm genom taranarak daha fazla genin hastalıkta rolü incelenmiş ve daha önce SS ile ilişkisi bilinmeyen genlerin SS ile ilişkisi gösterilmiştir.
Sonuç ve Tartışma: SS’in genlerle ilişkisini daha iyi ortaya koymak ve insanlardan elde edilen verilerin pekiştirilmesi için spontan ve genetiği modifiye edilmiş hayvan modelleriyle de çalışmalar yürütülmektedir. Bu çalışmada daha önce diğer otoimmün hastalıklarda incelenen genler ile GWAS çalışmalarında ilişkili bulunan genlerin SS ile ilişkisi, ilişkili bulunan genler üzerinden hastalığın patogenezisine katkısı olabilecek olası yolaklar irdelenmiştir.

Anahtar Kelimeler

Gen polimorfizmi, genetik toksik etkiler, genotoksisite, otoimmün hastalık, Sjögren sendromu

Kaynakça

• 1. Mackay, F., Woodcock, S.A., Lawton, P., Ambrose, C., Baetscher, M., Schneider, P., Tschopp, J., Browning, J.L. (1999). Mice transgenic for BAFF develop lymphocytic disorders along with autoimmune manifestations. Journal of Experimental Medicine, 190(11), 1697-1710. [CrossRef]
• 2. Pers, J.O., Daridon, C., Devauchelle, V., Jousse, S., Saraux, A., Jamin, C., Youinou, P. (2005). BAFF overexpression is associated with autoantibody production in autoimmune diseases. Annals of the New York Academy of Sciences, 1050, 34-39. [CrossRef]
• 3. Ittah, M., Miceli-Richard, C., Eric, G.J., Lavie, F., Lazure, T., Ba, N., Sellam, J., Lepajolec, C., Mariette, X. (2006). B cell-activating factor of the tumor necrosis factor family (BAFF) is expressed under stimulation by interferon in salivary gland epithelial cells in primary Sjögren’s syndrome. Arthritis Research & Therapy, 8(2), R51. [CrossRef]
• 4. Sarigul, M., Yazisiz, V., Bassorgun, C.I., Ulker, M., Avci, A.B., Erbasan, F., Gelen, T., Gorczynski, R.M., Terzioglu, E. (2010). The numbers of Foxp3 + Treg cells are positively correlated with higher grade of infiltration at the salivary glands in primary Sjogren’s syndrome. Lupus, 19(2), 138-145. [CrossRef]
• 5. Higgs, R., Gabhann, J.N., Larbi, N.B., Breen, E.P., Fitzgerald, K.A., Jefferies, C.A. (2008). The E3 ubiquitin ligase Ro52 negatively regulates IFN-beta production post-pathogen recognition by polyubiquitin-mediated degradation of IRF3. Journal of Immunology, 181(3), 1780-1786. [CrossRef]
• 6. Higgs, R., Lazzari, E., Wynne, C., Gabhann, J.N., Espinosa, A., Wahren-Herlenius, M., Jefferies, C.A. (2010). Self protection from anti-viral responses-Ro52 promotes degradation of the transcription factor IRF7 downstream of the viral Toll-Like receptors. PloS One, 5(7), e11776. [CrossRef]
• 7. Oke, V., Wahren-Herlenius, M. (2012). The immunobiology of Ro52 (TRIM21) in autoimmunity: A critical review. Journal of Autoimmunity, 39(1-2), 77-82. [CrossRef]
• 8. Yoshimi, R., Chang, T.H., Wang, H., Atsumi, T., Morse, H.C., Ozato, K. (2009). Gene disruption study reveals a nonredundant role for TRIM21/Ro52 in NF-kappaB-dependent cytokine expression in fibroblasts. Jornal of Immunology, 182(12), 7527-7538. [CrossRef]
• 9. Mallery, D.L., McEwan, W.A., Bidgood, S.R., Towers, G.J., Johnson, C.M., James, L.C. (2010). Antibodies mediate intracellular immunity through tripartite motif-containing 21 (TRIM21). Proceedings of the National Academy of Sciences of the United States of America, 107(46), 19985-19990. [CrossRef]
• 10. Jauharoh, S.N.A., Saegusa, J., Sugimoto, T., Ardianto, B., Kasagi, S., Sugiyama, D., Kurimoto, C., Tokuno, O., Nakamachi, Y., Kumagai, S., Kawano, S. (2012). SS-A/Ro52 promotes apoptosis by regulating Bcl-2 production. Biochemical and Biophysical Research Communications, 417(1), 582-587. [CrossRef]
• 11. Espinosa, A., Zhou, W., Ek, M., Hedlund, M., Brauner, S., Popovic, K., Horvath, L., Wallerskog, T., Oukka, M., Nyberg, F., Kuchroo, V.K., Wahren-Herlenius, M. (2006). The Sjogren’s syndrome-associated autoantigen Ro52 is an E3 ligase that regulates proliferation and cell death. Journal of Immunology, 176(10), 6277-6285. [CrossRef]
• 12. Seror, R., Ravaud, P., Bowman, S.J., Baron, G., Tzioufas, A., Theander, E., Gottenberg, J.E., Bootsma, H., Mariette, X., Vitali, C., EULAR Sjögren’s Task Force. (2010). EULAR Sjogren’s syndrome disease activity index: Development of a consensus systemic disease activity index for primary Sjogren’s syndrome. Annals of the Rheumatic Diseases, 69(6), 1103-1109. [CrossRef]
• 13. Espinosa, A., Dardalhon, V., Brauner, S., Ambrosi, A., Higgs, R., Quintana, F.J., Sjöstrand, M., Eloranta, M.L., Gabhann, J.N., Winqvist, O., Sundelin, B., Jefferies, C.A., Rozell, B., Kuchroo, V.K., Wahren-Herlenius, M. (2009). Loss of the lupus autoantigen Ro52/Trim21 induces tissue inflammation and systemic autoimmunity by disregulating the IL-23-Th17 pathway. Journal of Experimental Medicine, 206(8), 1661-1671. [CrossRef]
• 14. Verhagen, A.P.M., Pruijn, G.J.M. (2011). Are the Ro RNP-associated Y RNAs concealing microRNAs? Y RNA-derived miRNAs may be involved in autoimmunity. BioEssays, 33(9), 674-682. [CrossRef]
• 15. Sandhya, P., Kurien, B.T., Danda, D., Scofield, R.H. (2017). Update on pathogenesis of Sjögren’s syndrome. Current Rheumatology Reviews, 13(1), 5-22. [CrossRef]
• 16. Bolstad, A.I., Wassmuth, R., Haga, H.J., Jonsson, R. (2001). HLA markers and clinical characteristics in Caucasians with primary Sjogren’s syndrome. The Journal of Rheumatology, 28(7), 1554-1562.
• 17. Perez, P., Anaya, J.M., Aguilera, S., Urzúa, U., Munroe, D., Molina, C., Hermoso, M.A., Cherry, J.M., Alliende, C., Olea, N., Ruiz-Narvaez, E., Gonzalez, M.J. (2009). Gene expression and chromosomal location for susceptibility to Sjogren’s syndrome. Journal of Autoimmunity, 33(2), 99-108. [CrossRef]
• 18. Bogdanos, D.P., Smyk, D.S., Rigopoulou, E.I., Mytilinaiou, M.G., Heneghan, M.A., Selmi, C., Gershwin, M.E. (2012). Twin studies in autoimmune disease: Genetics, gender and environment. Journal of Autoimmunity, 38(2-3), J156-J169. [CrossRef]
• 19. Besana, C., Salmaggi, C., Pellegrino, C., Pierro, L., Vergani, S., Faravelli, A., Rugarli, C. (1991). Chronic bilateral dacryo-adenitis in identical twins: A possible incomplete form of Sjögren syndrome. European Journal of Pediatrics, 150(9), 652-655. [CrossRef]
• 20. Bolstad, A.I., Haga, H.J., Wassmuth, R., Jonsson, R. (2000). Monozygotic twins with primary Sjogren’s syndrome. The Journal of Rheumatology, 27(9), 2264-2266.
• 21. Houghton, K.M., Cabral, D.A., Petty, R.E., Tucker, L.B. (2005). Primary Sjögren’s syndrome in dizygotic adolescent twins: One case with lymphocytic interstitial pneumonia. The Journal of Rheumatology, 32(8), 1603-1606.
• 22. Reveille, J.D., Wilson, R.W., Provost, T.T., Bias, W.B., Arnett, F.C. (1984). Primary Sjögren’s syndrome and other autoimmune diseases in families. Prevalence and immunogenetic studies in six kindreds. Annals of Internal Medicine, 101(6), 748-756. [CrossRef]
• 23. Anaya, J.M., Tobon, G.J., Vega, P., Castiblanco, J. (2006) Autoimmune disease aggregation in families with primary Sjögren’s syndrome. The Journal of Rheumatology, 33(11), 2227-2234.
• 24. Chused, T.M., Kassan, S.S., Opelz, G., Moutsopoulos, H.M., Terasaki, P.I. (1977). Sjögren’s syndrome association with HLA-Dw3. The New England Journal of Medicine, 296(16), 895-897. [CrossRef]
• 25. Klein, J., Sato, A. (2000). The HLA system. First of two parts. The New England Journal of Medicine, 343(10), 702-709.
• 26. Sumitran-Holgersson, S. (2008). Beyond ABO and human histocompatibility antigen: Other histocompatibility antigens with a role in transplantation. Current Opinion in Organ Transplantation, 13(4), 425-429. [CrossRef]
• 27. Howell, W.M., Carter, V., Clark, B. (2010). The HLA system: Immunobiology, HLA typing, antibody screening and crossmatching techniques. Journal of Clinical Pathology, 63(5), 387-390. [CrossRef]
• 28. Guggenbuhl, P., Jean, S., Jego, P., Grosbois, B., Chalès, G., Semana, G., Lancien, G., Veillard, E., Pawlotsky, P.Y., Perdriger, A. (1998). Primary Sjögren’s syndrome: Role of the HLA-DRB1*0301-*1501 heterozygotes. The Journal of Rheumatology, 25(5), 900-905.
• 29. Jean, S., Quelvennec, E., Alizadeh, M., Guggenbuhl, P., Birebent, B., Perdriger, A., Grosbois, B., Pawlotsky, P.Y., Semana, G. (1998) DRB1*15 and DRB1*03 extended haplotype interaction in primary Sjögren’s syndrome genetic susceptibility. Clinical and Experimental Rheumatology, 16, 725-728.
• 30. Loiseau, P., Lepage, V., Djelal, F., Busson, M., Tamouza, R., Raffoux, C., Menkes, C.J., Meyer, O., Charron, D., Goldberg, D. (2001). HLA class I and class II are both associated with the genetic predisposition to primary Sjögren syndrome. Human Immunology, 62(7), 725-731. [CrossRef]
• 31. Anaya, J.M., Correa, P.A., Mantilla, R.D., Arcos-Burgos, M. (2002). TAP, HLA-DQB1, and HLA-DRB1 polymorphism in Colombian patients with primary Sjögren’s syndrome. Seminars in Arthritis and Rheumatism, 31(6), 396-405. [CrossRef]
• 32. Gottenberg, J.E., Busson, M., Loiseau, P., Cohen-Solal, J., Lepage, V., Charron, D., Sibilia, J., Mariette, X. (2003). In primary Sjögren’s syndrome, HLA class II is associated exclusively with autoantibody production and spreading of the autoimmune response. Arthritis and Rheumatism, 48(8), 2240-2245. [CrossRef]
• 33. Nakken, B., Jonsson, R., Brokstad, K.A., Omholt, K., Nerland, A.H., Haga, H.J., Halse, A.K. (2008). Associations of MHC class II alleles in Norwegian primary Sjögren’s syndrome patients: Implications for development of autoantibodies to the Ro52 autoantigen. Scandinavian Journal of Immunology, 54, 428-433. [CrossRef]
• 34. Hernández Molina, G., Vargas Alarcón, G., Rodríguez Pérez, J., Martínez-Rodríguez, N., Lima, G., Sánchez-Guerrero, J. (2015). High resolution HLA analysis of primary and secondary Sjögren’s syndrome: A common immunogenetic background in Mexican patients. Rheumatology International, 35(4), 643-649. [CrossRef]
• 35. Huang, R., Yin, J., Chen, Y., Deng, F., Chen, J., Gao, X., Liu, Z., Yu, X., Zheng, J. (2015). The amino acid variation within the binding pocket 7 and 9 of HLA-DRB1 molecules are associated with primary Sjögren’s syndrome. Journal of Autoimmunity, 57, 53-59. [CrossRef]
• 36. Lagha, A., Messadi, A., Boussaidi, S., Kochbati, S., Tazeghdenti, A., Ghazouani, E., Almawi, W.Y., Yacoubi-Loueslati, B. (2016). HLA DRB1/DQB1 alleles and DRB1-DQB1 haplotypes and the risk of rheumatoid arthritis in Tunisians: A population-based case-control study. HLA, 88, 100-109. [CrossRef]
• 37. Cruz-Tapias, P., Rojas-Villarraga, A., Maier-Moore, S., Anaya, J.M. (2012). HLA and Sjögren’s syndrome susceptibility. A meta-analysis of worldwide studies. Autoimmunity Reviews, 11(4), 281-287. [CrossRef]
• 38. Lessard, C.J., Li, H., Adrianto, I., Ice, J.A., Rasmussen, A., Grundahl, K.M., Kelly, J.A., Dozmorov, M.G., Miceli-Richard, C., Bowman, S., Lester, S., Eriksson, P., Eloranta, M.L., Brun, J.G., Goransson, L.G., Harboe, E., Guthridge, J.M., Kaufman, K.M., Kvarnström, M., Jazebi, H., Graham, D.S.C., Grandits, M.E., Nazmul-Hossain, A.N.M., Patel, K., Adler, A.J., Maier-Moore, J.S., Farris, A.D., Brennan, M.T., Lessard, J.A., Chodosh, J., Gopalakrishnan, R., Hefner, K.S., Houston, G.D., Huang, A.J.W., Hughes, P.J., Lewis, D.M., Radfar, L., Rohrer, M.D., Stone, D.U., Wren, J.D., Vyse, T.J., Gaffney, P.M., James, J.A., Omdal, R., Wahren-Herlenius, M., Illei, G.G., Witte T., Jonsson, R., Rischmueller, M., Rönnblom, L., Nordmark, G., Ng, W.F., UK Primary Sjögren’s Syndrome Registry, Mariette, X., Anaya, J.M., Rhodus, N.L., Segal, B.M., Scofield, R.H., Montgomery, C.G., Harley, J.B., Sivils, K.L. (2013). Variants at multiple loci implicated in both innate and adaptive immune responses are associated with Sjögren’s syndrome. Nature Genetics, 45(11), 1284-1292. [CrossRef]
• 39. Li, Y., Zhang, K., Chen, H., Sun, F., Xu, J., Wu, Z., Li, P., Zhang, L., Du, Y., Luan, H., Li, X., Wu, L., Li, H., Wu, H., Li, X., Li, X., Zhang, X., Gong, L., Dai, L., Sun, L., Zuo, X., Xu, J., Gong, H., Li, Z., Tong, S., Wu, M., Li, X., Xiao, W., Wang, G., Zhu, P., Shen, M., Liu, S., Zhao, D., Liu, W., Wang, Y., Huang, C., Jiang, Q., Liu, G., Liu, B., Hu, S., Zhang, W., Zhang, Z., You, X., Li, M., Hao, W., Zhao, C., Leng, X., Bi, L., Wang, Y., Zhang, F., Shi, Q., Qi, W., Zhang, X., Jia, Y., Su, J., Li, Q., Hou, Y., Wu, Q., Xu, D., Zheng, W., Zhang, M., Wang, Q., Fei, Y., Zhang, X., Li, J., Jiang, Y., Tian, X., Zhao, L., Wang, L., Zhou, B., Li, Y., Zhao, Y., Zeng, X., Ott, J., Wang, J., Zhang, F. (2013). A genome-wide association study in Han Chinese identifies a susceptibility locus for primary Sjögren’s syndrome at 7q11.23. Nature Genetics, 45(11), 1361-1365. [CrossRef]
• 40. Fernando, M.M.A., Stevens, C.R., Walsh, E.C., De Jager, P.L., Goyette, P., Plenge, R.M., Vyse, T.J., Rioux, J.D. (2008). Defining the role of the MHC in autoimmunity: A review and pooled analysis. PLoS Genetics, 4(4), e1000024. [CrossRef]
• 41. Harley, J.B., Reichlin, M., Arnett, F.C., Alexander, E.L., Bias, W.B., Provost, T.T. (1986). Gene interaction at HLA-DQ enhances auto-antibody production in primary Sjögren’s syndrome. Science, 232(4754), 1145-1147. [CrossRef]
• 42. Mohammed, K., Pope, J., Le Riche, N., Brintnell, W., Cairns, E., Coles, R., Bell, D.A. (2009). Association of severe inflammatory polyarthritis in primary Sjögren’s syndrome: Clinical, serologic, and HLA analysis. The Journal of Rheumatology, 36(9), 1937-1942. [CrossRef]
• 43. Mathur, A.N., Chang, H.C., Zisoulis, D.G., Stritesky, G.L., Yu, Q., O’Malley, J.T., Kapur, R., Levy, D.E., Kansas, G.S., Kaplan, M.H. (2007). Stat3 and Stat4 direct development of IL-17-secreting Th cells. Journal of Immunology, 178(8), 4901-4907. [CrossRef]
• 44. Korman, B.D., Kastner, D.L., Gregersen, P.K., Remmers, E.F. (2008). STAT4: Genetics, mechanisms, and implications for autoimmunity. Current Allergy and Asthma Reports, 8(5), 398-403. [CrossRef]
• 45. Liu, Q.F., Li, Y., Zhao, Q.H., Wang, Z.Y., Hu, S., Yang, C.Q., Ye, K., Li, L. (2015). Association of STAT4 rs7574865 polymorphism with susceptibility to inflammatory bowel disease: A systematic review and meta-analysis. Clinics and Research in Hepatology and Gastroenterology, 39(5), 627-636. [CrossRef]
• 46. Korman, B.D., Alba, M.I., Le, J.M., Alevizos, I., Smith, J.A., Nikolov, N.P., Kastner, D.L., Remmers, E.F., Illei, G.G. (2008b). Variant form of STAT4 is associated with primary Sjögren’s syndrome. Genes and Immunity, 9(3), 267-270. [CrossRef]
• 47. Palomino-Morales, R.J., Diaz-Gallo, L.M., Witte, T., Anaya, J.M., Martin, J. (2010). Influence of STAT4 polymorphism in primary Sjogren’s syndrome. The Journal of Rheumatology, 37(5), 1016-1019. [CrossRef]
• 48. Gestermann, N., Mekinian, A., Comets, E., Loiseau, P., Puechal, X., Hachulla, E., Gottenberg, J.E., Mariette, X., Miceli-Richard, C. (2010). STAT4 is a confirmed genetic risk factor for Sjögren’s syndrome and could be involved in type 1 interferon pathway signaling. Genes and Immunity, 11(5), 432-438. [CrossRef]
• 49. Novak, A.J., Slager, S.L., Fredericksen, Z.S., Wang, A.H., Manske, M.M., Ziesmer, S., Liebow, M., Macon, W.R., Dillon, S.R., Witzig, T.E., Cerhan, J.R., Ansell, S.M. (2009). Genetic variation in B-cell-activating factor is associated with an increased risk of developing B-cell non-Hodgkin lymphoma. Cancer Research, 69 (10), 4217-4224. [CrossRef]
• 50. Lavie, F., Miceli-Richard, C., Quillard, J., Roux, S., Leclerc, P., Mariette X. (2004). Expression of BAFF (BLyS) in T cells infiltrating labial salivary glands from patients with Sjogren’s syndrome. The Journal of Pathology, 202(4), 496-502. [CrossRef]
• 51. Nossent, J.C., Lester, S., Zahra, D., Mackay, C.R., Rischmueller, M. (2008). Polymorphism in the 5´regulatory region of the B-lymphocyte activating factor gene is associated with the Ro/La autoantibody response and serum BAFF levels in primary Sjogren’s syndrome. Rheumatology, 47(9), 1311-1316. [CrossRef]
• 52. Hildebrand, J.M., Luo, Z., Manske, M.K., Price-Troska, T., Ziesmer, S.C., Lin, W., Hostager, B.S., Slager, S.L., Witzig, T.E., Ansell, S.M., Cerhan, J.R., Bishop, G.A., Novak, A.J. (2010). A BAFF-R mutation associated with non-Hodgkin lymphoma alters TRAF recruitment and reveals new insights into BAFF-R signaling. Journal of Experimental Medicine, 207(12), 2569-2579. [CrossRef]
• 53. Baek, A., Park, H.J., Na, S.J., Shim, D.S., Moon, J.S., Yang, Y., Choi, Y.C. (2012) The expression of BAFF in the muscles of patients with dermatomyositis. Journal of Neuroimmunology, 249(1-2), 96-100. [CrossRef]
• 54. Ohmatsu, H., Sugaya, M., Miyagaki, T., Suga, H., Fujita, H., Asano, Y., Sato, S. (2012). BAFF levels are increased in lesional skin and sera in patients with cutaneous T-cell lymphoma. The British Journal of Dermatology, 167(2), 359-367. [CrossRef]
• 55. Zhai, K., Tian, X., Wu, C., Lu, N., Chang, J., Huang, L., Zhang, T., Zhou, Y., Qiao, Y., Yu, D., Tan, W., Chen, J., Lin, D. (2012). Cytokine BAFF gene variation is associated with survival of patients with T-cell lymphomas. Clinical Cancer Research, 18(8), 2250-2256. [CrossRef]
• 56. Mackay, F., Browning, J.L. (2002). BAFF: A fundamental survival factor for B cells. Nature Reviews Immunology, 2(7), 465-475. [CrossRef]
• 57. Vincent, F.B., Saulep-Easton, D., Figgett, W.A., Fairfax, K.A., Mackay, F. (2013). The BAFF/APRIL system: emerging functions beyond B cell biology and autoimmunity. Cytokine & Growth Factor Reviews, 24(3), 203-215. [CrossRef]
• 58. Novak, A.J., Grote, D.M., Ziesmer, S.C., Kline, M.P., Manske, M.K., Slager, S., Witzig, T.E., Shanafelt, T., Call, T.G., Kay, N.E., Jelinek, D.F., Cerhan, J.R., Gross, J.A., Harder, B., Dillon, S.R., Ansell, S.M. (2006). Elevated serum B-lymphocyte stimulator levels in patients with familial lymphoproliferative disorders. Journal of Clinical Oncology, 24(6), 983-987. [CrossRef]
• 59. Mackay, F., Schneider, P. (2009). Cracking the BAFF code. Nature Reviews Immunology, 9(7), 491-502. [CrossRef]
• 60. Manetta, J., Bina, H., Ryan, P., Fox, N., Witcher, D.R., Kikly, K. (2014). Generation and characterization of tabalumab, a human monoclonal antibody that neutralizes both soluble and membrane-bound B-cell activating factor. Journal of Inflammation Research, 2014(7), 121-131. [CrossRef]
• 61. Schneider, P. (2005). The role of APRIL and BAFF in lymphocyte activation. Current Opinion in Immunology, 17(3), 282-289. [CrossRef]
• 62. Gross, J.A., Johnston, J., Mudri, S., Enselman, R., Dillon, S.R., Madden, K., Xu, W., Parrish-Novak, J., Foster, D., Lofton-Day, C., Moore, M., Littau, A., Grossman, A., Haugen, H., Foley, K., Blumberg, H., Harrison, K., Kindsvogel, W, Clegg, C.H. (2000). TACI and BCMA are receptors for a TNF homologue implicated in B-cell autoimmune disease. Nature, 404(6781), 995-999. [CrossRef]
• 63. Nezos, A., Gravani, F., Tassidou, A., Kapsogeorgou, E.K., Voulgarelis, M., Koutsilieris, M., Crow, M.K., Mavragani, C.P. (2015). Type I and II interferon signatures in Sjögren’s syndrome pathogenesis: Contributions in distinct clinical phenotypes and Sjögren’s related lymphomagenesis. Journal of Autoimmunity, 63, 47-58. [CrossRef]
• 64. Thompson, N., Isenberg, D., Jury, E.C., Ciurtin, C. (2016). Exploring BAFF: Its expression, receptors and contribution to the immunopathogenesis of Sjögren’s syndrome. Rheumatology, 55, 15. [CrossRef]
• 65. Novak, A.J., Bram, R.J., Kay, N.E., Jelinek, D.F. (2002). Aberrant expression of B-lymphocyte stimulator by B chronic lymphocytic leukemia cells: a mechanism for survival. Blood, 100(8), 2973-2979. [CrossRef]
• 66. Graham, R.R., Cotsapas, C., Davies, L., Hackett, R., Lessard, C.J., Leon, J.M., Burtt, N.P., Guiducci, C., Parkin, M., Gates, C., Plenge, R.M., Behrens, T.W., Wither, J.E., Rioux, J.D., Fortin, P.R., Graham, D.C., Wong, A.K., Vyse, T.J., Daly, M.J., Altshuler, D., Moser, K.L., Gaffney, P.M. (2008). Genetic variants near TNFAIP3 on 6q23 are associated with systemic lupus erythematosus. Nature Genetics, 40(9), 1059-1061. [CrossRef]
• 67. Thomson, W., Barton, A., Ke, X., Eyre, S., Hinks, A., Bowes, J., Donn, R., Symmons, D., Hider, S., Bruce, I.N., Wellcome Trust Case Control Consortium, Wilson, A.G., Marinou, I., Morgan, A., Emery, P., YEAR Consortium, Carter, A., Steer, S., Hocking, L., Reid, D.M., Wordsworth, P., Harrison, P., Strachan, D., Worthington, J. (2007). Rheumatoid arthritis association at 6q23. Nature Genetics, 39(12), 1431-1433. [CrossRef]
• 68. Wellcome Trust Case Control Consortium (2007). Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature, 447, 661-678. [CrossRef]
• 69. Musone, S.L., Taylor, K.E., Lu, T.T., Nititham, J., Ferreira, R.C., Ortmann, W., Shifrin, N., Petri, M.A., Kamboh, M.I., Manzi S., Seldin, M.F., Gregersen, P.K., Behrens, T.W., Ma, A., Kwok, P.Y., Criswell, L.A. (2008). Multiple polymorphisms in the TNFAIP3 region are independently associated with systemic lupus erythematosus. Nature Genetics, 40(9), 1062-1064. [CrossRef]
• 70. Fung, E.Y.M.G., Smyth, D.J., Howson, J.M.M, Cooper, J.D., Walker, N.M., Stevens, H., Wicker, L.S., Todd, J.A. (2009). Analysis of 17 autoimmune disease-associated variants in type 1 diabetes identifies 6q23/TNFAIP3 as a susceptibility locus. Genes and Immunity, 10(2), 188-191. [CrossRef]
• 71. Gateva, V., Sandling, J.K., Hom, G., Taylor, K.E., Chung, S.A., Sun, X., Ortmann, W., Kosoy, R., Ferreira, R.C., Nordmark, G., Gunnarsson, I., Svenungsson, E., Padyukov, L., Sturfelt, G., Jönsen, A., Bengtsson, A.A., Rantapaa-Dahlqvist, S., Baechler, E.C., Brown, E.E., Alarcon, G.S., Edberg, J.C., Ramsey-Gaoldman, R., McGwin Jr, G., Reveille, J.D., Vila, L.M., Kimberly, R.P., Manzi, S., Petri, M.A., Lee, A., Gregersen, P.K., Seldin, M.F., Rönnblom, L., Criswell, L.A., Syvanen, A.-C., Behrens, T.W., Graham, R.R. (2009). A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus. Nature Genetics, 41(11), 1228-1233. [CrossRef]
• 72. Nair, R.P., Duffin, K.C., Helms, C., Ding, J., Stuart, P.E., Goldgar, D., Gudjonsson, J.E., Li, Y., Tejasvi, T., Feng, B.J., Ruether, A., Schreiber, S., Weichenthal, M., Gladman, D., Rahman, P., Schrodi, S.J., Prahalad, S., Guthery, S.L., Fischer, J., Liao, W., Kwok, P.-Y., Menter, A., Lathrop, G.M., Wise, C.A., Begovich, A.B., Voorhees, J.J., Elder, J.T., Krueger, G.G., Bowcock, A.M., Abecasis, G.R., Collaborative Association Study of Psoriasis. (2009) Genome-wide scan reveals association of psoriasis with IL-23 and NF-kappa B pathways. Nature Genetics, 41(2), 199-204. [CrossRef]
• 73. Dieude, P., Guedj, M., Wipff, J., Ruiz, B., Riemekasten, G., Matucci-Cerinic, M., Melchers, I., Hachulla, E., Airo, P., Diot, E., Hunzelmann, N., Cabane, J., Mouthon, L., Cracowski, J.L., Riccieri, V., Distler, J., Meyer, O., Kahan, A., Boileau, C., Allanore, Y. (2010). Association of the TNFAIP3 rs5029939 variant with systemic sclerosis in the European Caucasian population. Annals of the Rheumatic Diseases, 69(11), 1958-1964. [CrossRef]
• 74. Allanore, Y., Saad, M., Dieude, P., Avouac, J., Distler, J.H., Amouyel, P., Matucci-Cerinic, M., Riemekasten, G., Airo, P., Melchers, I., Hachulla, E., Cusi, D., Wichmann, H.E., Wipff, J., Lambert, J.C.,Hunzelmann, N., Tiev, K., Caramaschi, P., Diot, E., Kowal-Bielecka, O., Valentini, G., Mouthon, L., Czirjak, L., Damjanov, N., Salvi, E., Conti, C., Müller, M., Müller-Ladner, U., Riccieri, V., Ruiz, B., Cracowski, J.L., Letenneur, L., Dupuy, A.M., Meyer, O., Kahan, A., Munnich, A., Boileau, C., Martinez, M. (2011). Genome-wide scan identifies TNIP1, PSORS1C1, and RHOB as novel risk loci for systemic sclerosis. PLoS Genetics, 7(7), e1002091. [CrossRef]
• 75. Musone, S.L., Taylor, K.E., Nititham, J., Chu, C., Poon, A., Liao, W., Lam, E.T., Ma, A., Kwok, P.Y., Criswell, L.A. (2011). Sequencing of TNFAIP3 and association of variants with multiple autoimmune diseases. Genes and Immunity, 12(3), 176-182. [CrossRef]
• 76. Nordmark, G., Wang, C., Vasaitis, L., Eriksson, P., Theander, E., Kvarnström, M., Forsblad-d’Elia, H., Jazebi, H., Sjöwall, C., Reksten, T.R., Brun, J.G., Jonsson, M.V., Johnsen, S.J., Wahren-Herlenius, M., Omdal, R., Jonsson, R., Bowman, S., Ng, W.F., Eloramta, M.L., Syvanen, A.C., UK Primary Sjögren’s Syndrome Registry. (2013). Association of genes in the NF-κB pathway with antibody-positive Primary Sjögren’s Syndrome. Scandinavian Journal of Immunology, 78(5), 447-454. [CrossRef]
• 77. Shimane, K., Kochi, Y., Horita, T., Ikari, K., Amano, H., Hirakata, M., Okamoto, A., Yamada, R., Myouzen, K., Suzuki, A., Kubo, M., Atsumi, T., Koike, T., Takasaki, Y., Momohara, S., Yamanaka, H., Nakamura, Y., Yamamoto, K. (2010). The association of a nonsynonymous single-nucleotide polymorphism in TNFAIP3 with systemic lupus erythematosus and rheumatoid arthritis in the Japanese population. Arthritis and Rheumatism, 62(2), 574-579. [CrosssRef]
• 78. Ramos, P.S., Criswell, L.S., Moser, K.L., Comeau, M.E., Williams, A.H., Pajewski, N.M. Chung, S.A., Graham, R.R., Zidovetzki, R., Kelly, J.A., Kaufman, K.M., Jacob, C.O., Vyse, T.J., Tsao, B.P., Kimberly, R.P., Gaffney, P.M., Alarcon-Riquelme, M.E., Harley, J.B., Langefeld, C.B., The International Consortium on the Genetics of Systemic Erythematosus. (2011). A comprehensive analysis of shared loci between systemic lupus erythematosus (SLE) and sixteen autoimmune diseases reveals limited genetic overlap. PLoS Genetics, 7(12), e1002406. [CrossRef]
• 79. Zhou, X.J., Lu, X.I., Nath, S.K., Lv, J.C, Zhu, S.N., Yang, H.Z., Qin, L.X., Zhao, M.H., Su, Y., Shen, N., Li, Z.G., Zhang, H. (2012). International Consortium on the Genetics of Systemic Lupus Erythematosus. (2012). Gene-gene interaction of BLK, TNFSF4, TRAF1, TNFAIP3, and REL in systemic lupus erythematosus. Arthritis and Rheumatism, 64(1), 222-231. [CrossRef]
• 80. Nezos, A., Gkioka, E., Koutsilieris, M., Voulgarelis, M., Tzioufas, A.G., Mavragani, P.M. (2018). TNFAIP3 F127C coding variation in Greek Primary Sjogren’s Syndrome patients. Journal of Immunology Research, 2018, 6923213. [CrossRef]
• 81. Ciccacci, C., Latini, A., Perricone, C., Conigliaro, P., Colafrancesco, S., Ceccarelli, F., Priori, R., Conti, F., Perricone, R., Novelli, G., Borgiani, P. (2019). TNFAIP3 gene polymorphisms in three common autoimmune diseases: Systemic lupus erythematosus, rheumatoid arthritis, and primary Sjogren Syndrome-association with disease susceptibility and clinical phenotypes in Italian patients. Journal of Immunology Research, 2019, 6728694. [CrossRef]
• 82. Safonova, T.N., Surnina, Z.V., Zaitseva, G.V., Burdennyi, A.M., Loginov, V.I. (2020). The role of polymorphic markers rs1478604, rs2292305, and rs2228262 in THBS1 gene in the development of autoimmune dry eye syndrome. Bulletin of Experimental Biology and Medicine, 169(5), 707-709. [CrossRef]
• 83. Burbelo, P.D., Ambatipudi, K., Alevizos, I. (2014). Genome-wide association studies in Sjögren’s syndrome: What do the genes tell us about disease pathogenesis? Autoimmunity Reviews, 13(7), 756-761. [CrossRef]
• 84. Markeljevic, J., Sarac, H., Bozina, N., Henigsberg, N., Simic, M., Cicin Sain, L. (2015). Serotonin transporter gene polymorphisms: Relation with platelet serotonin level in patients with primary Sjogren’s syndrome. Journal of Neuroimmunology, 282, 104-109. [CrossRef]
• 85. Soto-Cárdenas, M.J., Gandía, M., Brito-Zerón, P., Arias, M.T., Armiger, N., Bové, A., Bosch, X., Retamozo, S., Akasbi, M., Perez-De-Lis, M., Gueitasi, H., Kostov, B., Perez-Alvarez, R., Siso-Almirall, A., Lozano, F., Ramos-Casals, M. (2015). Etiopathogenic role of surfactant protein D in the clinical and immunological expression of Primary Sjögren Syndrome. The Journal of Rheumatology, 42(1), 111-118. [CrossRef]
• 86. Burn, G.L., Svensson, L., Sanchez-Blanco, C., Saini, M., Cope, A.P. (2011). Why is PTPN22 a good candidate susceptibility gene for autoimmune disease? Why is PTPN22 a good candidate susceptibility gene for autoimmune disease? FEBS Letters, 585(23), 3689-3698. [CrossRef]
• 87. Ivashkiv, L.B. (2013). PTPN22 in autoimmunity: Different cell and different way. Immunity, 39(1), 91-93. [CrossRef]
• 88. Wang, Y., Shaked, I., Stanford, S.M., Zhou, W, Curtsinger, J.M., Mikulski, Z., Shaheen, Z.R., Cheng, G., Sawatzke, K., Campbell, A.M., Auger, J.L., Bilgic, H., Shoyama, F.M., Schmeling, D.O., Balfour Jr, H.H., Hasegawa, K., Chan, A.C., Corbett, J.A., Binstadt, B.A., Mescher, M.F., Ley, K., Bottini, N., Peterson, E.J. (2013). The autoimmunity-associated gene PTPN22 potentiates toll-like receptor-driven, type 1 interferon-dependent immunity. Immunity, 39(1), 111-122. [CrossRef]
• 89. Zheng, J., Ibrahim, S., Petersen, F., Yu, X. (2012). Meta-analysis reveals an association of PTPN22 C1858T with autoimmune diseases, which depends on the localization of the affected tissue. Genes and Immunity, 13(8), 641-652. [CrossRef]
• 90. Koutsilieris, M., Moutsopoulos, H.M., Mavragani, C.P. (2016). Increased frequency of the PTPN22W* variant in primary Sjögren’s Syndrome: Association with low type I IFN scores. Clinical Immunology, 173, 157-160. [CrossRef]
• 91. Lavoie, T.N., Lee, B.H., Nguyen, C.Q. (2011) Current concepts: mouse models of Sjögren’s syndrome. Journal of Biomedicine and Biotechnology, 2011, 549107. [CrossRef]
• 92. Fang, T.J., Li, R.N., Lin, Y.Z., Lin, C.H., Tseng, C.C., Sung, W.Y., Qu, T.T., Wu, C.C., Yen, J.H. (2021). Association of F11R polymorphisms and gene expression with primary Sjögren’s syndrome patients. International Journal of Rheumatic Diseases, 24(5), 681-686. [CrossRef]
• 93. Gibbs, R.A., Weinstock, G.M., Metzker, M.L., Muzny, D.M., Sodergren, E.J., Scherer, S., Scott, G., Steffen, D., Worley, K.C., Burch, P.E., Okwuonu, G., Hines, S., Lewis, L., DeRamo, C., Delgado, O., Dugan-Rocha, S., Miner, G., Morgan, M., Hawes, A., Gill, R., Celera, Holt, R.A., Adams, M.D., Amanatides, P.G., Baden-Tillson, H., Barnstead, M., Chin, S., Evans, C.A., Ferriera, S., Fosler, C., Glodek, A., Gu, Z., Jennings, D., Kraft, C.L., Nguyen, T., Pfannkoch, C.M., Sitter, C., Sutton, G.G., Venter, J.C., Woodage, T., Smith, D., lee, h.-M., Gustafson, E., Cahill, P., Kana, A., Doucette-Stamm, L., Weinstock, K., Fechtel, K., Weiss, R.B., Dunn, D.M., Green, E.D., Blakesley, R.W., Bouffard, G.G., De Jong, P.J., Osoegawa, K., Zhu, B., Marra, M., Schein, J., Bosdet, I., Fjell, C., Jones, S., Krzywinski, M., Mathewson, C., Siddiqui, A., Wye, N., McPherson, J., Zhao, S., Fraser, C.M., Shetty, J., Shatsman, S., Geer, K., Chen, Y., Abramzon, S., Nierman, W.C., Havlak, P.H., Chen, R., Durbin, K.J., Egan, A., Ren, Y., Song, X.-Z., Li, B., Liu, Y., Qin, X., Cawley, S., Worley, K.C., Cooney, A.J., D’Souza, L.M., Martin, K., Wu, J.Q., Gonzalez-Garay, M.L., Jackson, A.R., Kalafus, K.J., McLeod, M.P., Milosavljevic, A., Virk, D., Volkov, A., Wheeler, D.A., Zhang, Z., Bailey, J.A., Eichler, E.E., Tuzun, E., Birney, E., Mongin, E., Ureta-Vidal, A., Woodwark, C., Zdobnov, E., Bork, P., Suyama, M., Torrents, D., Alexandersson, M., Trask, B.J., Young, J.M., Huang, H., Wang, H., Xing, H., Daniels, S., Gietzen, D, Schmidt, J., Stevens, K., Vitt, U., Wingrove, J., Camara, F., Alba, M.M., Abril, J.F., Guigo, R., Smit, A., Dubchak, I., Rubin, E.M., Couronne, O., Poliakov, A., Hübner, N., Ganten, D., Goesele, C., Hummel, O., Kreitler, T., Lee, Y.-A., Monti, J., Schulz, H., Zimdahl, H., Himmelbauer, H., Lehrach, H., Jacob, H.J., Bromberg, S., Gullings-Handley, J., Jensen-Seaman, M.I., Kwitek, A.E., Lazar, J., Pasko, D., Tonellato, P.J., Twigger, S.M., Ponting, C.P., Duarte, J.M., Rice, S., Goodstadt, L., Beatson, S.A., Emes, R.D., Winter, E.E., Webber, C., Brandt, P., Nyakatura, G., Adetobi, M., Chiaromonte, F., Elnitski, L., Eswara, P., Hardison, R.C., Hou, M., Kolbe, D., Makova, K., Miller, W., Nekrutenko, A., Riemer, C., Schwartz, S., Taylor, J., Yang, S., Zhang, Y., Lindpaitner, K., Andrews, T.D., Caccamo, M., Clamp, M., Clarke, L., Curwen, V., Durbin, R., Eyras, E., Searle, S.M., Cooper, G.M., Batzoglou, S., Brudno, M., Sidow, A., Stone, E.A., Venter, J.C., Payseur, B.A., Bourque, G., Lopez-Otin, C., Puente, X.S., Chakrabarti, K., Chatterji, S., Dewey, C., Pachter, L., Bray, N., Yap, V.B., Caspi, A., Tesler, G., Pevzner, P.A., Haussler, D., Roskin, K.M., Baertsch, R., Clawson, H., Furey, T.S., Hinrichs, A.S., Karolchik, D., Kent, W.J., Rosenbloom, K.R., Trumbower, H., Weirauch, M., Cooper, D.N., Stenson, P.D., Ma, B., Brent, M., Arumugam, M., Shteynberg, D., Copley, R.R., Taylor, M.S., Riethman, H., Mudunuri, U., Peterson, J., Guyer, M., Felsenfeld, A., Old, S., Mockrin, S., Collins, F., Rat Genome Sequencing Project Consortium. (2004). Genome sequence of the Brown Norway rat yields insights into mammalian evolution. Nature, 428(6982), 493-521. [CrossRef]
• 94. Delaleu, N., Nguyen, C.Q., Peck, A.B., Jonsson, R. (2011). Sjögren’s syndrome: Studying the disease in mice. Arthritis Research & Therapy, 13(3), 217. [CrossRef]
• 95. Konttinen, Y.T., Tensing, E.K., Laine, M., Porola, P., Tornwall, J., Hukkanen, M. (2005). Abnormal distribution of aquaporin-5 in salivary glands in the NOD mouse model for Sjögren’s syndrome. The Journal of Rheumatology, 32(6), 1071-1075.
• 96. Winer, S., Astsaturov, I., Cheung, R., Tsui, H., Song, A., Gaedigk, R., Winer, D., Sampson, A., McKerlie, C., Bookman, A., Dosch, H.M. (2002). Primary Sjögren’s syndrome and deficiency of ICA69. Lancet, 360(9339), 1063-1069. [CrossRef]
• 97. Cha, S., Nagashima, H., Brown, V.B., Peck, A.B., Humphreys-Beher, M.G. (2002). Two NOD Idd-associated intervals contribute synergistically to the development of autoimmune exocrinopathy (Sjögren’s syndrome) on a healthy murine background. Arthritis and Rheumatism, 46(5), 1390-1398. [CrossRef]
• 98. Park, Y.S., Gauna, A.E., Cha, S. (2015). Mouse models of primary Sjögren’s syndrome. Current Pharmaceutical Design, 21(18), 2350-2364. [CrossRef]
• 99. Vosters, J.L., Landek-Salgado, M.A., Yin, H., Swaim, W.D., Kimura, H., Tak, P.P., Caturegli, P., Chiorini, J.A. (2009). Interleukin-12 induces salivary gland dysfunction in transgenic mice, providing a new model of Sjögren's syndrome. Arthritis and Rheumatism, 60(12), 3633-3641. [CrossRef]