Targeting primary Sjögren’s syndrome

References

• Fox RI. Sjögren's syndrome. Lancet. 2005;366(9482):321–31.
   PubMed Web of Science ®Google Scholar
• Tsuboi H, Asashima H, Takai C, Hagiwara S, Hagiya C, Yokosawa M, et al. Primary and secondary surveys on epidemiology of Sjögren's syndrome in Japan. Mod Rheumatol. 2014;24(3):464–70.
   PubMed Web of Science ®Google Scholar
• Qin B, Wang J, Yang Z, Yang M, Ma N, Huang F, et al. Epidemiology of primary Sjögren's syndrome: a systematic review and meta-analysis. Ann Rheum Dis. 2015;74(11):1983–9.
   PubMed Web of Science ®Google Scholar
• Skopouli FN, Dafni U, Ioannidis JP, Moutsopoulos HM. Clinical evolution, and morbidity and mortality of primary Sjogren's syndrome. Semin Arthritis Rheum. 2000;29(5):296–304.
   PubMed Web of Science ®Google Scholar
• Voulgarelis M, Dafni UG, Isenberg DA, Moutsopoulos HM. Malignant lymphoma in primary Sjogren's syndrome: a multicenter, retrospective, clinical study by the European Concerted Action on Sjogren's Syndrome. Arthritis Rheum. 1999;42(8):1765–72.
   PubMed Web of Science ®Google Scholar
• Theander E, Henriksson G, Ljungberg O, Mandl T, Manthorpe R, Jacobsson LT. Lymphoma and other malignancies in primary Sjogren's syndrome: a cohort study on cancer incidence and lymphoma predictors. Ann Rheum Dis. 2006;65(6):796–803.
   PubMed Web of Science ®Google Scholar
• Wen S, Shimizu N, Yoshiyama H, Mizugaki Y, Shinozaki F, Takada K. Association of Epstein-Barr virus (EBV) with Sjogren's syndrome: differential EBV expression between epithelial cells and lymphocytes in salivary glands. Am J Pathol 1996;149(5):1511–7.
   PubMed Web of Science ®Google Scholar
• Triantafyllopoulou A, Moutsopoulos H. Persistent viral infection in primary Sjogren's syndrome: review and perspectives. Clinic Rev Allerg Immunol. 2007;32(3):210–4.
   PubMed Web of Science ®Google Scholar
• Weller ML, Gardener MR, Bogus ZC, Smith MA, Astorri E, Michael DG, et al. Hepatitis delta virus detected in salivary glands of Sjogren's syndrome patients and recapitulates a Sjogren's syndrome-like phenotype in vivo. Pathog Immun. 2016;1(1):12–40.
   PubMedGoogle Scholar
• Vitali C, Bombardieri S, Jonsson R, Moutsopoulos HM, Alexander EL, Carsons SE, et al. Classification criteria for Sjogren's syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. Ann Rheum Dis. 2002;61(6):554–8.
   PubMed Web of Science ®Google Scholar
• Shiboski SC, Shiboski CH, Criswell L, Baer A, Challacombe S, Lanfranchi H, et al. American College of Rheumatology classification criteria for Sjogren's syndrome: a data-driven, expert consensus approach in the Sjogren's International Collaborative Clinical Alliance cohort. Arthritis Care Res. 2012;64(4):475–87.
   PubMed Web of Science ®Google Scholar
• Shiboski CH, Shiboski SC, Seror R, Criswell LA, Labetoulle M, Lietman TM, et al. 2016 American College of Rheumatology/European League against rheumatism classification criteria for primary Sjogren's syndrome: a consensus and data-driven methodology involving three international patient cohorts. Ann Rheum Dis. 2017;76(1):9–16.
   PubMed Web of Science ®Google Scholar
• Shiboski CH, Shiboski SC, Seror R, Criswell LA, Labetoulle M, Lietman TM, et al. 2016 American College of Rheumatology/European league against rheumatism classification criteria for primary Sjogren's syndrome: a consensus and data-driven methodology involving three international patient cohorts. Arthritis Rheumatol. 2017;69(1):35–45.
   PubMed Web of Science ®Google Scholar
• Sumida T, Azuma N, Moriyama M, Takahashi H, Asashima H, Honda F, et al. Clinical practice guideline for Sjogren's syndrome 2017. Mod Rheumatol. 2018;28(3):383–408.
   PubMed Web of Science ®Google Scholar
• Sumida T, Tsuboi H, Iizuka M, Asashima H, Matsumoto I. Anti-M3 muscarinic acetylcholine receptor antibodies in patients with Sjogren's syndrome. Mod Rheumatol. 2013;23(5):841–5.
   PubMed Web of Science ®Google Scholar
• Qin Q, Wang H, Wang HZ, Huang YL, Li H, Zhang WW, et al. Diagnostic accuracy of anti-alpha-fodrin antibodies for primary Sjogren's syndrome. Mod Rheumatol. 2014;24(5):793–7.
   PubMed Web of Science ®Google Scholar
• Fayyaz A, Kurien BT, Scofield RH. Autoantibodies in Sjögren's Syndrome. Rheum Dis Clin North Am. 2016;42(3):419–34.
   PubMed Web of Science ®Google Scholar
• Suzuki Y, Fujii H, Nomura H, Mizushima I, Yamada K, Yamagishi M, et al. Impact of double positive for anti-centromere and anti-SS-a/Ro antibodies on clinicopathological characteristics of primary Sjogren's syndrome: a retrospective cohort study. Mod Rheumatol 2018;1–7.
   Web of Science ®Google Scholar
• Birnbaum J, Hoke A, Lalji A, Calabresi P, Bhargava P, Casciola-Rosen L. Anti-calponin-3 autoantibodies: a new specificity in patients with Sjogren's syndrome. Arthritis Rheumatol 2018;70(10):1610–6.
   PubMed Web of Science ®Google Scholar
• Miyasato-Isoda M, Waguri M, Yamada Y, Miyano A, Wada Y. Anti-Ro52 antibody level is an important marker of fetal congenital heart block risk in anti-Ro/SSA antibody positive pregnancy. Mod Rheumatol. 2018;28(4):690–6.
   PubMed Web of Science ®Google Scholar
• Ramos-Casals M, Tzioufas AG, Stone JH, Siso A, Bosch X. Treatment of primary Sjögren syndrome: a systematic review. JAMA. 2010;304(4):452–60.
   PubMed Web of Science ®Google Scholar
• Deveci H, Kobak S. The efficacy of topical 0.05 % cyclosporine A in patients with dry eye disease associated with Sjögren's syndrome. Int Ophthalmol. 2014;34(5):1043–8.
   PubMed Web of Science ®Google Scholar
• Tauber J, Karpecki P, Latkany R, Luchs J, Martel J, Sall K, et al. Lifitegrast ophthalmic solution 5.0% versus placebo for treatment of dry eye disease: results of the randomized phase III OPUS-2 study. Ophthalmology 2015;122(12):2423–31.
   PubMed Web of Science ®Google Scholar
• Nakayamada S, Saito K, Nakatsuka K, Nakano K, Tokunaga M, Sawamukai N, et al. Efficacy of mizoribine treatment in patients with Sjögren's syndrome: an open pilot trial. Mod Rheumatol. 2003;13(4):339–45.
   PubMedGoogle Scholar
• Nakayamada S, Saito K, Umehara H, Ogawa N, Sumida T, Ito S, et al. Efficacy and safety of mizoribine for the treatment of Sjögren's syndrome: a multicenter open-label clinical trial . Mod Rheumatol. 2007;17(6):464–9.
   PubMedGoogle Scholar
• Sugai S, Takahashi H, Ohta S, Nishinarita M, Takei M, Sawada S, et al. Efficacy and safety of rebamipide for the treatment of dry mouth symptoms in patients with Sjogren's syndrome: a double-blind placebo-controlled multicenter trial. Mod Rheumatol. 2009;19(2):114–24.
   PubMed Web of Science ®Google Scholar
• Hamad AA, Lodi G, Porter S, Fedele S, Mercadante V. Interventions for dry mouth and hyposalivation in Sjogren's syndrome: a systematic review and meta-analysis. Oral Dis 2018.
   PubMedGoogle Scholar
• Mariette X, Criswell LA. Primary Sjögren's Syndrome. N Engl J Med. 2018;378(10):931–9.
   PubMed Web of Science ®Google Scholar
• Christodoulou MI, Kapsogeorgou EK, Moutsopoulos HM. Characteristics of the minor salivary gland infiltrates in Sjögren's syndrome. J Autoimmun. 2010;34(4):400–7.
   PubMed Web of Science ®Google Scholar
• Gottenberg JE, Seror R, Miceli-Richard C, Benessiano J, Devauchelle-Pensec V, Dieude P, et al. Serum levels of beta2-microglobulin and free light chains of immunoglobulins are associated with systemic disease activity in primary Sjogren's syndrome. Data at enrollment in the prospective ASSESS cohort. PLoS One. 2013;8(5):e59868.
   PubMed Web of Science ®Google Scholar
• Theander E, Jonsson R, Sjostrom B, Brokstad K, Olsson P, Henriksson G. Prediction of Sjogren's syndrome years before diagnosis and identification of patients with early onset and severe disease course by autoantibody profiling. Arthritis Rheumatol. 2015;67(9):2427–36.
   PubMed Web of Science ®Google Scholar
• 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(2):100–9.
   PubMed Web of Science ®Google Scholar
• 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(11):1284–92.
   PubMed Web of Science ®Google Scholar
• Theander E, Vasaitis L, Baecklund E, Nordmark G, Warfvinge G, Liedholm R, et al. Lymphoid organisation in labial salivary gland biopsies is a possible predictor for the development of malignant lymphoma in primary Sjogren's syndrome. Ann Rheum Dis. 2011;70(8):1363–8.
   PubMed Web of Science ®Google Scholar
• Risselada AP, Looije MF, Kruize AA, Bijlsma JW, van Roon JA. The role of ectopic germinal centers in the immunopathology of primary Sjogren's syndrome: a systematic review. Semin Arthritis Rheum. 2013;42(4):368–76.
   PubMed Web of Science ®Google Scholar
• Daridon C, Pers JO, Devauchelle V, Martins-Carvalho C, Hutin P, Pennec YL, et al. Identification of transitional type II B cells in the salivary glands of patients with Sjogren's syndrome. Arthritis Rheum. 2006;54(7):2280–8.
   PubMed Web of Science ®Google Scholar
• Vossenkamper A, Lutalo PM, Spencer J. Translational Mini-Review Series on B cell subsets in disease. Transitional B cells in systemic lupus erythematosus and Sjogren's syndrome: clinical implications and effects of B cell-targeted therapies. Clin Exp Immunol. 2012;167(1):7–14.
   PubMed Web of Science ®Google Scholar
• Nguyen CQ, Kim H, Cornelius JG, Peck AB. Development of Sjogren's syndrome in nonobese diabetic-derived autoimmune-prone C57BL/6.NOD-Aec1Aec2 mice is dependent on complement component-3. J Immunol. 2007;179(4):2318–29.
   PubMed Web of Science ®Google Scholar
• Shen L, Gao C, Suresh L, Xian Z, Song N, Chaves LD, et al. Central role for marginal zone B cells in an animal model of Sjogren's syndrome. Clin Immunol. 2016;168:30–6.
   PubMed Web of Science ®Google Scholar
• Bohnhorst JO, Bjorgan MB, Thoen JE, Natvig JB, Thompson KM. Bm1-Bm5 classification of peripheral blood B cells reveals circulating germinal center founder cells in healthy individuals and disturbance in the B cell subpopulations in patients with primary Sjogren's syndrome. J Immunol. 2001;167(7):3610–8.
   PubMed Web of Science ®Google Scholar
• Hansen A, Gosemann M, Pruss A, Reiter K, Ruzickova S, Lipsky PE, et al. Abnormalities in peripheral B cell memory of patients with primary Sjogren's syndrome. Arthritis Rheum. 2004;50(6):1897–908.
   PubMed Web of Science ®Google Scholar
• Roberts ME, Kaminski D, Jenks SA, Maguire C, Ching K, Burbelo PD, et al. Primary Sjogren's syndrome is characterized by distinct phenotypic and transcriptional profiles of IgD + unswitched memory B cells. Arthritis Rheumatol. 2014;66(9):2558–69.
   PubMed Web of Science ®Google Scholar
• Ishioka-Takei E, Yoshimoto K, Suzuki K, Nishikawa A, Yasuoka H, Yamaoka K, et al. Increased proportion of a CD38(high)IgD(+) B cell subset in peripheral blood is associated with clinical and immunological features in patients with primary Sjogren's syndrome. Clin Immunol. 2018;187:85–91.
   PubMed Web of Science ®Google Scholar
• Mauri C, Menon M. Human regulatory B cells in health and disease: therapeutic potential. J Clin Invest. 2017;127(3):772–9.
   PubMed Web of Science ®Google Scholar
• Wang RX, Yu CR, Dambuza IM, Mahdi RM, Dolinska MB, Sergeev YV, et al. Interleukin-35 induces regulatory B cells that suppress autoimmune disease. Nat Med. 2014;20(6):633–41.
   PubMed Web of Science ®Google Scholar
• Fogel O, Riviere E, Seror R, Nocturne G, Boudaoud S, Ly B, et al. Role of the IL-12/IL-35 balance in patients with Sjögren syndrome. J Allergy Clin Immunol. 2018;142(1):258–68 e5.
   PubMed Web of Science ®Google Scholar
• Kong L, Ogawa N, Nakabayashi T, Liu GT, D'Souza E, McGuff HS, et al. Fas and Fas ligand expression in the salivary glands of patients with primary Sjogren's syndrome. Arthritis Rheum. 1997;40(1):87–97.
   PubMedGoogle Scholar
• Varin MM, Guerrier T, Devauchelle-Pensec V, Jamin C, Youinou P, Pers JO. In Sjogren's syndrome, B lymphocytes induce epithelial cells of salivary glands into apoptosis through protein kinase C delta activation. Autoimmun Rev. 2012;11(4):252–8.
   PubMed Web of Science ®Google Scholar
• Kong L, Robinson CP, Peck AB, Vela-Roch N, Sakata KM, Dang H, et al. Inappropriate apoptosis of salivary and lacrimal gland epithelium of immunodeficient NOD-scid mice. Clin Exp Rheumatol. 1998;16(6):675–81.
   PubMed Web of Science ®Google Scholar
• Ping L, Ogawa N, Sugai S. Novel role of CD40 in Fas-dependent apoptosis of cultured salivary epithelial cells from patients with Sjogren's syndrome. Arthritis Rheum. 2005;52(2):573–81.
   PubMed Web of Science ®Google Scholar
• Dimitriou ID, Kapsogeorgou EK, Moutsopoulos HM, Manoussakis MN. CD40 on salivary gland epithelial cells: high constitutive expression by cultured cells from Sjogren's syndrome patients indicating their intrinsic activation. Clin Exp Immunol. 2002;127(2):386–92.
   PubMed Web of Science ®Google Scholar
• Nakamura H, Kawakami A, Tominaga M, Migita K, Kawabe Y, Nakamura T, et al. Expression of CD40/CD40 ligand and Bcl-2 family proteins in labial salivary glands of patients with Sjögren's syndrome. Lab Invest. 1999;79(3):261–9.
   PubMed Web of Science ®Google Scholar
• Kawakami A, Nakashima K, Tamai M, Nakamura H, Iwanaga N, Fujikawa K, et al. Toll-like receptor in salivary glands from patients with Sjogren's syndrome: functional analysis by human salivary gland cell line. J Rheumatol. 2007;34(5):1019–26.
   PubMed Web of Science ®Google Scholar
• Spachidou MP, Bourazopoulou E, Maratheftis CI, Kapsogeorgou EK, Moutsopoulos HM, Tzioufas AG, et al. Expression of functional Toll-like receptors by salivary gland epithelial cells: increased mRNA expression in cells derived from patients with primary Sjogren's syndrome. Clin Exp Immunol. 2007;147(3):497–503.
   PubMed Web of Science ®Google Scholar
• Manoussakis MN, Dimitriou ID, Kapsogeorgou EK, Xanthou G, Paikos S, Polihronis M, et al. Expression of B7 costimulatory molecules by salivary gland epithelial cells in patients with Sjogren's syndrome. Arthritis Rheum. 1999;42(2):229–39.
   PubMedGoogle Scholar
• Kapsogeorgou EK, Moutsopoulos HM, Manoussakis MN. Functional expression of a costimulatory B7.2 (CD86) protein on human salivary gland epithelial cells that interacts with the CD28 receptor, but has reduced binding to CTLA4. J Immunol. 2001;166(5):3107–13.
   PubMed Web of Science ®Google Scholar
• Thabet Y, Le Dantec C, Ghedira I, Devauchelle V, Cornec D, Pers JO, et al. Epigenetic dysregulation in salivary glands from patients with primary Sjogren's syndrome may be ascribed to infiltrating B cells. J Autoimmun. 2013;41:175–81.
   PubMed Web of Science ®Google Scholar
• Fox RI, Bumol T, Fantozzi R, Bone R, Schreiber R. Expression of histocompatibility antigen HLA-DR by salivary gland epithelial cells in Sjogren's syndrome. Arthritis Rheum. 1986;29(9):1105–11.
   PubMedGoogle Scholar
• Kawanami T, Sawaki T, Sakai T, Miki M, Iwao H, Nakajima A, et al. Skewed production of IL-6 and TGFbeta by cultured salivary gland epithelial cells from patients with Sjogren's syndrome. PLoS One. 2012;7(10):e45689.
   PubMed Web of Science ®Google Scholar
• Baldini C, Santini E, Rossi C, Donati V, Solini A. The P2X7 receptor-NLRP3 inflammasome complex predicts the development of non-Hodgkin's lymphoma in Sjogren's syndrome: a prospective, observational, single-centre study. J Intern Med. 2017;282(2):175–86.
   PubMed Web of Science ®Google Scholar
• Xanthou G, Polihronis M, Tzioufas AG, Paikos S, Sideras P, Moutsopoulos HM. "Lymphoid" chemokine messenger RNA expression by epithelial cells in the chronic inflammatory lesion of the salivary glands of Sjogren's syndrome patients: possible participation in lymphoid structure formation. Arthritis Rheum. 2001;44(2):408–18.
   PubMed Web of Science ®Google Scholar
• Barone F, Bombardieri M, Rosado MM, Morgan PR, Challacombe SJ, De Vita S, et al. CXCL13, CCL21, and CXCL12 expression in salivary glands of patients with Sjogren's syndrome and MALT lymphoma: association with reactive and malignant areas of lymphoid organization. J Immunol. 2008;180(7):5130–40.
   PubMed Web of Science ®Google Scholar
• Sumida T, Tsuboi H, Iizuka M, Nakamura Y, Matsumoto I. Functional role of M3 muscarinic acetylcholine receptor (M3R) reactive T cells and anti-M3R autoantibodies in patients with Sjogren's syndrome. Autoimmun Rev. 2010;9(9):615–7.
   PubMed Web of Science ®Google Scholar
• Joachims ML, Leehan KM, Lawrence C, Pelikan RC, Moore JS, Pan Z, et al. Single-cell analysis of glandular T cell receptors in Sjogren's syndrome. JCI Insight. 2016;1(8).
   PubMed Web of Science ®Google Scholar
• Haneji N, Nakamura T, Takio K, Yanagi K, Higashiyama H, Saito I, et al. Identification of alpha-fodrin as a candidate autoantigen in primary Sjogren's syndrome. Science. 1997;276(5312):604–7.
   PubMed Web of Science ®Google Scholar
• Winer S, Astsaturov I, Cheung R, Tsui H, Song A, Gaedigk R, et al. Primary Sjögren's syndrome and deficiency of ICA69. Lancet. 2002;360(9339):1063–9.
   PubMed Web of Science ®Google Scholar
• Scofield RH, Asfa S, Obeso D, Jonsson R, Kurien BT. Immunization with short peptides from the 60-kDa Ro antigen recapitulates the serological and pathological findings as well as the salivary gland dysfunction of Sjogren's syndrome. J Immunol. 2005;175(12):8409–14.
   PubMed Web of Science ®Google Scholar
• Dudek NL, Maier S, Chen ZJ, Mudd PA, Mannering SI, Jackson DC, et al. T cell epitopes of the La/SSB autoantigen in humanized transgenic mice expressing the HLA class II haplotype DRB1*0301/DQB1*0201. Arthritis Rheum. 2007;56(10):3387–98.
   PubMedGoogle Scholar
• Li J, Ha YM, Ku NY, Choi SY, Lee SJ, Oh SB, et al. Inhibitory effects of autoantibodies on the muscarinic receptors in Sjögren's syndrome. Lab Invest. 2004;84(11):1430–8.
   PubMed Web of Science ®Google Scholar
• Naito Y, Matsumoto I, Wakamatsu E, Goto D, Ito S, Tsutsumi A, et al. Altered peptide ligands regulate muscarinic acetylcholine receptor reactive T cells of patients with Sjogren's syndrome. Ann Rheum Dis. 2006;65(2):269–71.
   PubMed Web of Science ®Google Scholar
• Iizuka M, Wakamatsu E, Tsuboi H, Nakamura Y, Hayashi T, Matsui M, et al. Pathogenic role of immune response to M3 muscarinic acetylcholine receptor in Sjogren's syndrome-like sialoadenitis. J Autoimmun. 2010;35(4):383–9.
   PubMed Web of Science ®Google Scholar
• Salomonsson S, Jonsson MV, Skarstein K, Brokstad KA, Hjelmstrom P, Wahren-Herlenius M, et al. Cellular basis of ectopic germinal center formation and autoantibody production in the target organ of patients with Sjogren's syndrome. Arthritis Rheum. 2003;48(11):3187–201.
   PubMed Web of Science ®Google Scholar
• Carubbi F, Alunno A, Cipriani P, Di Benedetto P, Ruscitti P, Berardicurti O, et al. Is minor salivary gland biopsy more than a diagnostic tool in primary Sjogrens syndrome? Association between clinical, histopathological, and molecular features: a retrospective study. Semin Arthritis Rheum. 2014;44(3):314–24.
   PubMed Web of Science ®Google Scholar
• Sene D, Ismael S, Forien M, Charlotte F, Kaci R, Cacoub P, et al. Ectopic germinal center-like structures in minor salivary gland biopsy tissue predict lymphoma occurrence in patients with primary Sjogren's syndrome. Arthritis Rheumatol. 2018;70(9):1481–1488.
   PubMed Web of Science ®Google Scholar
• Szabo K, Papp G, Barath S, Gyimesi E, Szanto A, Zeher M. Follicular helper T cells may play an important role in the severity of primary Sjögren's syndrome. Clin Immunol. 2013;147(2):95–104.
   PubMed Web of Science ®Google Scholar
• Bombardieri M, Barone F, Humby F, Kelly S, McGurk M, Morgan P, et al. Activation-induced cytidine deaminase expression in follicular dendritic cell networks and interfollicular large B cells supports functionality of ectopic lymphoid neogenesis in autoimmune sialoadenitis and MALT lymphoma in Sjogren's syndrome. J Immunol. 2007;179(7):4929–38.
   PubMed Web of Science ®Google Scholar
• Bombardieri M, Lewis M, Pitzalis C. Ectopic lymphoid neogenesis in rheumatic autoimmune diseases. Nat Rev Rheumatol. 2017;13(3):141–54.
   PubMed Web of Science ®Google Scholar
• Nocturne G, Seror R, Fogel O, Belkhir R, Boudaoud S, Saraux A, et al. CXCL13 and CCL11 serum levels and lymphoma and disease activity in primary Sjogren's syndrome. Arthritis Rheumatol. 2015;67(12):3226–33.
   PubMed Web of Science ®Google Scholar
• Nurieva R, Yang XO, Martinez G, Zhang Y, Panopoulos AD, Ma L, et al. Essential autocrine regulation by IL-21 in the generation of inflammatory T cells. Nature 2007;448(7152):480–3.
   PubMed Web of Science ®Google Scholar
• Crotty S. T follicular helper cell differentiation, function, and roles in disease. Immunity. 2014;41(4):529–42.
   PubMed Web of Science ®Google Scholar
• Szabo K, Papp G, Szanto A, Tarr T, Zeher M. A comprehensive investigation on the distribution of circulating follicular T helper cells and B cell subsets in primary Sjogren's syndrome and systemic lupus erythematosus. Clin Exp Immunol. 2016;183(1):76–89.
   PubMed Web of Science ®Google Scholar
• Li XY, Wu ZB, Ding J, Zheng ZH, Li XY, Chen LN, et al. Role of the frequency of blood CD4(+) CXCR5(+) CCR6(+) T cells in autoimmunity in patients with Sjögren's syndrome. Biochem Biophys Res Commun. 2012;422(2):238–44.
   PubMed Web of Science ®Google Scholar
• Kang KY, Kim HO, Kwok SK, Ju JH, Park KS, Sun DI, et al. Impact of interleukin-21 in the pathogenesis of primary Sjogren's syndrome: increased serum levels of interleukin-21 and its expression in the labial salivary glands. Arthritis Res Ther. 2011;13(5):R179.
   PubMed Web of Science ®Google Scholar
• Gong YZ, Nititham J, Taylor K, Miceli-Richard C, Sordet C, Wachsmann D, et al. Differentiation of follicular helper T cells by salivary gland epithelial cells in primary Sjogren's syndrome. J Autoimmun. 2014;51:57–66.
   PubMed Web of Science ®Google Scholar
• Verstappen GM, Kroese FG, Meiners PM, Corneth OB, Huitema MG, Haacke EA, et al. B cell depletion therapy normalizes circulating follicular Th cells in primary Sjogren syndrome. J Rheumatol. 2017;44(1):49–58.
   PubMed Web of Science ®Google Scholar
• Blokland SLM, Hillen MR, Kruize AA, Meller S, Homey B, Smithson GM, et al. Increased CCL25 and T helper cells expressing CCR9 in the salivary glands of patients with primary Sjogren's syndrome: potential new axis in lymphoid neogenesis. Arthritis Rheumatol. 2017;69(10):2038–51.
   PubMed Web of Science ®Google Scholar
• Youinou P, Pers JO. Disturbance of cytokine networks in Sjögren's syndrome. Arthritis Res Ther. 2011;13(4):227.
   PubMed Web of Science ®Google Scholar
• Miossec P, Korn T, Kuchroo VK. Interleukin-17 and type 17 helper T cells. N Engl J Med. 2009;361(9):888–98.
   PubMed Web of Science ®Google Scholar
• Moriyama M, Hayashida JN, Toyoshima T, Ohyama Y, Shinozaki S, Tanaka A, et al. Cytokine/chemokine profiles contribute to understanding the pathogenesis and diagnosis of primary Sjogren's syndrome. Clin Exp Immunol. 2012;169(1):17–26.
   PubMed Web of Science ®Google Scholar
• Vosters JL, Landek-Salgado MA, Yin H, Swaim WD, Kimura H, Tak PP, et al. Interleukin-12 induces salivary gland dysfunction in transgenic mice, providing a new model of Sjogren's syndrome. Arthritis Rheum. 2009;60(12):3633–41.
   PubMedGoogle Scholar
• Fleige H, Ravens S, Moschovakis GL, Bolter J, Willenzon S, Sutter G, et al. IL-17-induced CXCL12 recruits B cells and induces follicle formation in BALT in the absence of differentiated FDCs. J Exp Med. 2014;211(4):643–51.
   PubMed Web of Science ®Google Scholar
• Ito T, Hanabuchi S, Wang YH, Park WR, Arima K, Bover L, et al. Two functional subsets of FOXP3+ regulatory T cells in human thymus and periphery. Immunity. 2008;28(6):870–80.
   PubMed Web of Science ®Google Scholar
• Nguyen CQ, Hu MH, Li Y, Stewart C, Peck AB. Salivary gland tissue expression of interleukin-23 and interleukin-17 in Sjogren's syndrome: findings in humans and mice. Arthritis Rheum. 2008;58(3):734–43.
   PubMed Web of Science ®Google Scholar
• Sakai A, Sugawara Y, Kuroishi T, Sasano T, Sugawara S. Identification of IL-18 and Th17 cells in salivary glands of patients with Sjogren's syndrome, and amplification of IL-17-mediated secretion of inflammatory cytokines from salivary gland cells by IL-18. J Immunol. 2008;181(4):2898–906.
   PubMed Web of Science ®Google Scholar
• Katsifis GE, Rekka S, Moutsopoulos NM, Pillemer S, Wahl SM. Systemic and local interleukin-17 and linked cytokines associated with Sjogren's syndrome immunopathogenesis. Am J Pathol. 2009;175(3):1167–77.
   PubMed Web of Science ®Google Scholar
• Ciccia F, Guggino G, Rizzo A, Ferrante A, Raimondo S, Giardina A, et al. Potential involvement of IL-22 and IL-22-producing cells in the inflamed salivary glands of patients with Sjogren's syndrome. Ann Rheum Dis. 2012;71(2):295–301.
   PubMed Web of Science ®Google Scholar
• Lavoie TN, Stewart CM, Berg KM, Li Y, Nguyen CQ. Expression of interleukin-22 in Sjogren's syndrome: significant correlation with disease parameters. Scand J Immunol. 2011;74(4):377–82.
   PubMed Web of Science ®Google Scholar
• Nguyen CQ, Yin H, Lee BH, Carcamo WC, Chiorini JA, Peck AB. Pathogenic effect of interleukin-17A in induction of Sjogren's syndrome-like disease using adenovirus-mediated gene transfer. Arthritis Res Ther. 2010;12(6):R220.
   PubMed Web of Science ®Google Scholar
• Voigt A, Esfandiary L, Wanchoo A, Glenton P, Donate A, Craft WF, et al. Sexual dimorphic function of IL-17 in salivary gland dysfunction of the C57BL/6.NOD-Aec1Aec2 model of Sjogren's syndrome. Sci Rep. 2016;6:38717.
   PubMed Web of Science ®Google Scholar
• Hjelmervik TO, Petersen K, Jonassen I, Jonsson R, Bolstad AI. Gene expression profiling of minor salivary glands clearly distinguishes primary Sjogren's syndrome patients from healthy control subjects. Arthritis Rheum. 2005;52(5):1534–44.
   PubMed Web of Science ®Google Scholar
• Wildenberg ME, van Helden-Meeuwsen CG, van de Merwe JP, Drexhage HA, Versnel MA. Systemic increase in type I interferon activity in Sjogren's syndrome: a putative role for plasmacytoid dendritic cells. Eur J Immunol. 2008;38(7):2024–33.
   PubMed Web of Science ®Google Scholar
• Bave U, Nordmark G, Lovgren T, Ronnelid J, Cajander S, Eloranta ML, et al. Activation of the type I interferon system in primary Sjogren's syndrome: a possible etiopathogenic mechanism. Arthritis Rheum. 2005;52(4):1185–95.
   PubMed Web of Science ®Google Scholar
• Brkic Z, Maria NI, van Helden-Meeuwsen CG, van de Merwe JP, van Daele PL, Dalm VA, et al. Prevalence of interferon type I signature in CD14 monocytes of patients with Sjogren's syndrome and association with disease activity and BAFF gene expression. Ann Rheum Dis. 2013;72(5):728–35.
   PubMed Web of Science ®Google Scholar
• Yao Y, Liu Z, Jallal B, Shen N, Rönnblom L. Type I interferons in Sjögren's syndrome. Autoimmun Rev. 2013;12(5):558–66.
   PubMed Web of Science ®Google Scholar
• Gottenberg J-E, Cagnard N, Lucchesi C, Letourneur F, Mistou S, Lazure T, et al. Activation of IFN pathways and plasmacytoid dendritic cell recruitment in target organs of primary Sjogren's syndrome. Proc Natl Acad Sci USA. 2006;103(8):2770–5.
   PubMed Web of Science ®Google Scholar
• Hall JC, Baer AN, Shah AA, Criswell LA, Shiboski CH, Rosen A, et al. Molecular subsetting of interferon pathways in Sjogren's syndrome. Arthritis Rheumatol. 2015;67(9):2437–46.
   PubMed Web of Science ®Google Scholar
• Guiducci C, Ghirelli C, Marloie-Provost MA, Matray T, Coffman RL, Liu YJ, et al. PI3K is critical for the nuclear translocation of IRF-7 and type I IFN production by human plasmacytoid predendritic cells in response to TLR activation. J Exp Med. 2008;205(2):315–22.
   PubMed Web of Science ®Google Scholar
• Bodewes ILA, Huijser E, van Helden-Meeuwsen CG, Tas L, Huizinga R, Dalm V, et al. TBK1: a key regulator and potential treatment target for interferon positive Sjogren's syndrome, systemic lupus erythematosus and systemic sclerosis. J Autoimmun. 2018;91:97–102.
   PubMed Web of Science ®Google Scholar
• Zhao J, Kubo S, Nakayamada S, Shimajiri S, Zhang X, Yamaoka K, et al. Association of plasmacytoid dendritic cells with B cell infiltration in minor salivary glands in patients with Sjogren's syndrome. Mod Rheumatol. 2016;26(5):716–24.
   PubMed Web of Science ®Google Scholar
• Manoussakis MN, Boiu S, Korkolopoulou P, Kapsogeorgou EK, Kavantzas N, Ziakas P, et al. Rates of infiltration by macrophages and dendritic cells and expression of interleukin-18 and interleukin-12 in the chronic inflammatory lesions of Sjogren's syndrome: correlation with certain features of immune hyperactivity and factors associated with high risk of lymphoma development. Arthritis Rheum. 2007;56(12):3977–88.
   PubMed Web of Science ®Google Scholar
• Baldini C, Rossi C, Ferro F, Santini E, Seccia V, Donati V, et al. The P2X7 receptor-inflammasome complex has a role in modulating the inflammatory response in primary Sjogren's syndrome. J Intern Med. 2013;274(5):480–9.
   PubMed Web of Science ®Google Scholar
• Chen Y, Deng F, Zheng J, Yin J, Huang R, Liu W, et al. High circulating level of interleukin-18 in patients with primary Sjogren's syndrome is associated with disease activity. Mod Rheumatol. 2016;26(1):156–8.
   PubMed Web of Science ®Google Scholar
• Vakrakou AG, Boiu S, Ziakas PD, Xingi E, Boleti H, Manoussakis MN. Systemic activation of NLRP3 inflammasome in patients with severe primary Sjögren's syndrome fueled by inflammagenic DNA accumulations. J Autoimmun. 2018;91:23–33.
   PubMed Web of Science ®Google Scholar
• Kayes TD, Weisman GA, Camden JM, Woods LT, Bredehoeft C, Downey EF, et al. New murine model of early onset autoimmune thyroid disease/hypothyroidism and autoimmune exocrinopathy of the salivary gland. J Immunol. 2016;197(6):2119–30.
   PubMed Web of Science ®Google Scholar
• Khalafalla MG, Woods LT, Camden JM, Khan AA, Limesand KH, Petris MJ, et al. P2X7 receptor antagonism prevents IL-1beta release from salivary epithelial cells and reduces inflammation in a mouse model of autoimmune exocrinopathy. J Biol Chem. 2017;292(40):16626–37.
   PubMed Web of Science ®Google Scholar
• Pijpe J, van Imhoff GW, Spijkervet FK, Roodenburg JL, Wolbink GJ, Mansour K, et al. Rituximab treatment in patients with primary Sjogren's syndrome: an open-label phase II study. Arthritis Rheum. 2005;52(9):2740–50.
   PubMedGoogle Scholar
• Meijer JM, Meiners PM, Vissink A, Spijkervet FK, Abdulahad W, Kamminga N, et al. Effectiveness of rituximab treatment in primary Sjogren's syndrome: a randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2010;62(4):960–8.
   PubMed Web of Science ®Google Scholar
• Carubbi F, Cipriani P, Marrelli A, Benedetto P, Ruscitti P, Berardicurti O, et al. Efficacy and safety of rituximab treatment in early primary Sjogren's syndrome: a prospective, multi-center, follow-up study. Arthritis Res Ther. 2013;15(5):R172.
   PubMed Web of Science ®Google Scholar
• Dass S, Bowman SJ, Vital EM, Ikeda K, Pease CT, Hamburger J, et al. Reduction of fatigue in Sjogren syndrome with rituximab: results of a randomised, double-blind, placebo-controlled pilot study. Ann Rheum Dis. 2008;67(11):1541–4.
   PubMed Web of Science ®Google Scholar
• Gottenberg JE, Cinquetti G, Larroche C, Combe B, Hachulla E, Meyer O, et al. Efficacy of rituximab in systemic manifestations of primary Sjogren's syndrome: results in 78 patients of the AutoImmune and Rituximab registry. Ann Rheum Dis. 2013;72(6):1026–31.
   PubMed Web of Science ®Google Scholar
• Hasegawa J, Hayami N, Hoshino J, Suwabe T, Sumida K, Mise K, et al. Cryoglobulinemic vasculitis with primary Sjögren's syndrome: a case report. Mod Rheumatol. 2018;28(3):570–4.
   PubMed Web of Science ®Google Scholar
• Delli K, Haacke EA, Kroese FG, Pollard RP, Ihrler S, van der Vegt B, et al. Towards personalised treatment in primary Sjogren's syndrome: baseline parotid histopathology predicts responsiveness to rituximab treatment. Ann Rheum Dis. 2016;75(11):1933–8.
   PubMed Web of Science ®Google Scholar
• Pijpe J, Meijer JM, Bootsma H, van der Wal JE, Spijkervet FK, Kallenberg CG, et al. Clinical and histologic evidence of salivary gland restoration supports the efficacy of rituximab treatment in Sjogren's syndrome. Arthritis Rheum. 2009;60(11):3251–6.
   PubMed Web of Science ®Google Scholar
• Devauchelle-Pensec V, Morvan J, Rat AC, Jousse-Joulin S, Pennec Y, Pers JO, et al. Effects of rituximab therapy on quality of life in patients with primary Sjogren's syndrome. Clin Exp Rheumatol. 2011;29(1):6–12.
   PubMed Web of Science ®Google Scholar
• Devauchelle-Pensec V, Mariette X, Jousse-Joulin S, Berthelot JM, Perdriger A, Puechal X, et al. Treatment of primary Sjogren syndrome with rituximab: a randomized trial. Ann Intern Med. 2014;160(4):233–42.
   PubMed Web of Science ®Google Scholar
• Bowman SJ, Everett CC, O'Dwyer JL, Emery P, Pitzalis C, Ng WF, et al. Randomized controlled trial of rituximab and cost-effectiveness analysis in treating fatigue and oral dryness in primary Sjogren's syndrome. Arthritis Rheumatol. 2017;69(7):1440–50.
   PubMed Web of Science ®Google Scholar
• 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 Sjogren's syndrome. Arthritis Rheumatol. 2015;67(6):1623–8.
   PubMed Web of Science ®Google Scholar
• Bootsma H, Kroese FGM, Vissink A. Editorial: Rituximab in the treatment of Sjögren's syndrome: is it the right or wrong drug? Arthritis Rheumatol. 2017;69(7):1346–9.
   PubMed Web of Science ®Google Scholar
• Lavie F, Miceli-Richard C, Quillard J, Roux S, Leclerc P, Mariette X. Expression of BAFF (BLyS) in T cells infiltrating labial salivary glands from patients with Sjogren's syndrome. J Pathol. 2004;202(4):496–502.
   PubMed Web of Science ®Google Scholar
• Daridon C, Devauchelle V, Hutin P, Le Berre R, Martins-Carvalho C, Bendaoud B, et al. Aberrant expression of BAFF by B lymphocytes infiltrating the salivary glands of patients with primary Sjogren's syndrome. Arthritis Rheum. 2007;56(4):1134–44.
   PubMed Web of Science ®Google Scholar
• Lavie F, Miceli-Richard C, Ittah M, Sellam J, Gottenberg JE, Mariette XB. cell activating factor of the tumour necrosis factor family expression in blood monocytes and T cells from patients with primary Sjogren's syndrome. Scand J Immunol. 2008;67(2):185–92.
   PubMed Web of Science ®Google Scholar
• Groom J, Kalled SL, Cutler AH, Olson C, Woodcock SA, Schneider P, et al. Association of BAFF/BLyS overexpression and altered B cell differentiation with Sjögren's syndrome. J Clin Invest. 2002;109(1):59–68.
   PubMed Web of Science ®Google Scholar
• Ittah M, Miceli-Richard C, Eric Gottenberg J, Lavie F, Lazure T, Ba N, et al. B cell-activating factor of the tumor necrosis factor family (BAFF) is expressed under stimulation by interferon in salivary gland epithelial cells in primary Sjogren's syndrome. Arthritis Res Ther 2006;8(2):R51.
   PubMed Web of Science ®Google Scholar
• Roescher N, Vosters JL, Alsaleh G, Dreyfus P, Jacques S, Chiocchia G, et al. Targeting the splicing of mRNA in autoimmune diseases: BAFF inhibition in Sjögren's syndrome as a proof of concept. Mol Ther. 2014;22(4):821–7.
   PubMed Web of Science ®Google Scholar
• 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(2):168–71.
   PubMed Web of Science ®Google Scholar
• Quartuccio L, Salvin S, Fabris M, Maset M, Pontarini E, Isola M, et al. BLyS upregulation in Sjogren's syndrome associated with lymphoproliferative disorders, higher ESSDAI score and B-cell clonal expansion in the salivary glands. Rheumatology (Oxford). 2013;52(2):276–81.
   PubMed Web of Science ®Google Scholar
• Mariette X, Seror R, Quartuccio L, Baron G, Salvin S, Fabris M, et al. Efficacy and safety of belimumab in primary Sjogren's syndrome: results of the BELISS open-label phase II study. Ann Rheum Dis. 2015;74(3):526–31.
   PubMed Web of Science ®Google Scholar
• Doerner T, Posch M, Wagner F, Hueser A, Fischer T, Mooney L, et al. Safety and efficacy of single dose VAY736 (anti-BAFF-R mAb) in patients with primary Sjögren’s syndrome (pSS) [abstract]. Arthritis Rheumatol. 2016;68(suppl 10).
   Google Scholar
• De Vita S, Quartuccio L, Salvin S, Picco L, Scott CA, Rupolo M, et al. Sequential therapy with belimumab followed by rituximab in Sjogren's syndrome associated with B-cell lymphoproliferation and overexpression of BAFF: evidence for long-term efficacy. Clin Exp Rheumatol. 2014;32(4):490–4.
   PubMed Web of Science ®Google Scholar
• Sieger N, Fleischer SJ, Mei HE, Reiter K, Shock A, Burmester GR, et al. CD22 ligation inhibits downstream B cell receptor signaling and Ca(2+) flux upon activation. Arthritis Rheum. 2013;65(3):770–9.
   PubMed Web of Science ®Google Scholar
• Steinfeld SD, Tant L, Burmester GR, Teoh NK, Wegener WA, Goldenberg DM, et al. Epratuzumab (humanised anti-CD22 antibody) in primary Sjögren's syndrome: an open-label phase I/II study . Arthritis Res Ther. 2006;8(4):R129.
   PubMed Web of Science ®Google Scholar
• Wallace DJ, Kalunian K, Petri MA, Strand V, Houssiau FA, Pike M, et al. Efficacy and safety of epratuzumab in patients with moderate/severe active systemic lupus erythematosus: results from EMBLEM, a phase IIb, randomised, double-blind, placebo-controlled, multicentre study. Ann Rheum Dis. 2014;73(1):183–90.
   PubMed Web of Science ®Google Scholar
• Gottenberg JE, Dorner T, Bootsma H, Devauchelle-Pensec V, Bowman SJ, Mariette X, et al. Efficacy of epratuzumab, an anti-CD22 monoclonal IgG antibody, in systemic lupus erythematosus patients with associated Sjogren's syndrome: post hoc analyses from the EMBODY trials. Arthritis Rheumatol. 2018;70(5):763–73.
   PubMed Web of Science ®Google Scholar
• Kamachi M, Kawakami A, Yamasaki S, Hida A, Nakashima T, Nakamura H, et al. Regulation of apoptotic cell death by cytokines in a human salivary gland cell line: distinct and synergistic mechanisms in apoptosis induced by tumor necrosis factor alpha and interferon gamma. J Lab Clin Med. 2002;139(1):13–19.
   PubMed Web of Science ®Google Scholar
• Zhou J, Kawai T, Yu Q. Pathogenic role of endogenous TNF-α in the development of Sjögren's-like sialadenitis and secretory dysfunction in non-obese diabetic mice. Lab Invest. 2017;97(4):458–67.
   PubMed Web of Science ®Google Scholar
• Mariette X, Ravaud P, Steinfeld S, Baron G, Goetz J, Hachulla E, et al. Inefficacy of infliximab in primary Sjogren's syndrome: results of the randomized, controlled trial of remicade in primary Sjogren's syndrome (TRIPSS). Arthritis Rheum. 2004;50(4):1270–6.
   PubMed Web of Science ®Google Scholar
• Zandbelt MM, de Wilde P, van Damme P, Hoyng CB, van de Putte L, van den Hoogen F. Etanercept in the treatment of patients with primary Sjögren's syndrome: a pilot study. J Rheumatol. 2004;31(1):96–101.
   PubMed Web of Science ®Google Scholar
• Sankar V, Brennan MT, Kok MR, Leakan RA, Smith JA, Manny J, et al. Etanercept in Sjogren's syndrome: a twelve-week randomized, double-blind, placebo-controlled pilot clinical trial. Arthritis Rheum. 2004;50(7):2240–5.
   PubMedGoogle Scholar
• Yamada A, Arakaki R, Kudo Y, Ishimaru N. Targeting IL-1 in Sjögren's syndrome. Expert Opin Ther Targets. 2013;17(4):393–401.
   PubMed Web of Science ®Google Scholar
• Chen YT, Nikulina K, Lazarev S, Bahrami AF, Noble LB, Gallup M, et al. Interleukin-1 as a phenotypic immunomodulator in keratinizing squamous metaplasia of the ocular surface in Sjogren's syndrome. Am J Pathol. 2010;177(3):1333–43.
   PubMed Web of Science ®Google Scholar
• Norheim KB, Harboe E, Goransson LG, Omdal R. Interleukin-1 inhibition and fatigue in primary Sjogren's syndrome–a double blind, randomised clinical trial. PLoS One. 2012;7(1):e30123.
   PubMed Web of Science ®Google Scholar
• Adler S, Korner M, Forger F, Huscher D, Caversaccio MD, Villiger PM. Evaluation of histologic, serologic, and clinical changes in response to abatacept treatment of primary Sjogren's syndrome: a pilot study. Arthritis Care Res (Hoboken). 2013;65(11):1862–8.
   PubMed Web of Science ®Google Scholar
• Meiners PM, Vissink A, Kroese FG, Spijkervet FK, Smitt-Kamminga NS, Abdulahad WH, et al. Abatacept treatment reduces disease activity in early primary Sjogren's syndrome (open-label proof of concept ASAP study). Ann Rheum Dis. 2014;73(7):1393–6.
   PubMed Web of Science ®Google Scholar
• Tsuboi H, Matsumoto I, Hagiwara S, Hirota T, Takahashi H, Ebe H, et al. Efficacy and safety of abatacept for patients with Sjogren's syndrome associated with rheumatoid arthritis: rheumatoid arthritis with orencia trial toward Sjogren's syndrome Endocrinopathy (ROSE) trial-an open-label, one-year, prospective study-Interim analysis of 32 patients for 24 weeks. Mod Rheumatol. 2015;25(2):187–93.
   PubMed Web of Science ®Google Scholar
• Tsuboi H, Matsumoto I, Hagiwara S, Hirota T, Takahashi H, Ebe H, et al. Effectiveness of abatacept for patients with Sjogren's syndrome associated with rheumatoid arthritis. An open label, multicenter, one-year, prospective study: ROSE (Rheumatoid Arthritis with Orencia Trial toward Sjogren's syndrome Endocrinopathy) trial. Mod Rheumatol. 2016;26(6):891–9.
   PubMed Web of Science ®Google Scholar
• Takahashi H, Tsuboi H, Yokosawa M, Asashima H, Hirota T, Kondo Y, et al. Diffusion-weighted magnetic resonance imaging of parotid glands before and after abatacept therapy in patients with Sjogren's syndrome associated with rheumatoid arthritis: utility to evaluate and predict response to treatment. Mod Rheumatol. 2018;28(2):300–7.
   PubMed Web of Science ®Google Scholar
• Roebuck KA, Finnegan A. Regulation of intercellular adhesion molecule-1 (CD54) gene expression. J Leukoc Biol. 1999;66(6):876–88.
   PubMed Web of Science ®Google Scholar
• Evans R, Patzak I, Svensson L, De Filippo K, Jones K, McDowall A, et al. Integrins in immunity. J Cell Sci. 2009;122(Pt 2):215–25.
   PubMed Web of Science ®Google Scholar
• Kapsogeorgou EK, Dimitriou ID, Abu-Helu RF, Moutsopoulos HM, Manoussakis MN. Activation of epithelial and myoepithelial cells in the salivary glands of patients with Sjogren's syndrome: high expression of intercellular adhesion molecule-1 (ICAM.1) in biopsy specimens and cultured cells. Clin Exp Immunol. 2001;124(1):126–33.
   PubMed Web of Science ®Google Scholar
• Mikulowska-Mennis A, Xu B, Berberian JM, Michie SA. Lymphocyte migration to inflamed lacrimal glands is mediated by vascular cell adhesion molecule-1/alpha(4)beta(1) integrin, peripheral node addressin/l-selectin, and lymphocyte function-associated antigen-1 adhesion pathways. Am J Pathol. 2001;159(2):671–81.
   PubMed Web of Science ®Google Scholar
• Roescher N, Vosters JL, Yin H, Illei GG, Tak PP, Chiorini JA. Effect of soluble ICAM-1 on a Sjögren's syndrome-like phenotype in NOD mice is disease stage dependent. PLoS One. 2011;6(5):e19962.
   PubMed Web of Science ®Google Scholar
• Li S, Wang H, Peng B, Zhang M, Zhang D, Hou S, et al. Efalizumab binding to the LFA-1 alphaL I domain blocks ICAM-1 binding via steric hindrance. Proc Natl Acad Sci USA. 2009;106(11):4349–54.
   PubMed Web of Science ®Google Scholar
• Molloy ES, Calabrese LH. Therapy: targeted but not trouble-free: efalizumab and PML. Nat Rev Rheumatol. 2009;5(8):418–9.
   PubMed Web of Science ®Google Scholar
• Holland EJ, Whitley WO, Sall K, Lane SS, Raychaudhuri A, Zhang SY, et al. Lifitegrast clinical efficacy for treatment of signs and symptoms of dry eye disease across three randomized controlled trials. Curr Med Res Opin. 2016;1–7.
   PubMed Web of Science ®Google Scholar
• Illei G. Clinical Investigations of Sjogren's Syndrome. Available from: http://grantome.com/grant/NIH/ZIA-DE000704-08 [last accessed 16 Nov 2018].
   Google Scholar
• Mauri C, Bosma A. Immune regulatory function of B cells. Annu Rev Immunol. 2012;30:221–41.
   PubMed Web of Science ®Google Scholar
• Goules A, Tzioufas AG, Manousakis MN, Kirou KA, Crow MK, Routsias JG. Elevated levels of soluble CD40 ligand (sCD40L) in serum of patients with systemic autoimmune diseases. J Autoimmun. 2006;26(3):165–71.
   PubMed Web of Science ®Google Scholar
• Roescher N, Vosters JL, Lai Z, Uede T, Tak PP, Chiorini JA. Local administration of soluble CD40:Fc to the salivary glands of non-obese diabetic mice does not ameliorate autoimmune inflammation. PLoS One. 2012;7(12):e51375.
   PubMed Web of Science ®Google Scholar
• Fisher B, Zeher M, Ng WF, Bombardieri M, Posch M, Papas AS, et al. The novel anti-CD40 monoclonal antibody CFZ533 shows beneficial effects in patients with primary Sjögren’s syndrome: a phase IIa double-blind, placebo-controlled randomized trial [abstract]. Arthritis Rheumatol. 2017;69(suppl 10).
   PubMedGoogle Scholar
• Drayton DL, Ying X, Lee J, Lesslauer W, Ruddle NH. Ectopic LT alpha beta directs lymphoid organ neogenesis with concomitant expression of peripheral node addressin and a HEV-restricted sulfotransferase. J Exp Med. 2003;197(9):1153–63.
   PubMed Web of Science ®Google Scholar
• Fava RA, Kennedy SM, Wood SG, Bolstad AI, Bienkowska J, Papandile A, et al. Lymphotoxin-beta receptor blockade reduces CXCL13 in lacrimal glands and improves corneal integrity in the NOD model of Sjogren's syndrome. Arthritis Res Ther. 2011;13(6):R182.
   PubMed Web of Science ®Google Scholar
• Gatumu MK, Skarstein K, Papandile A, Browning JL, Fava RA, Bolstad AI. Blockade of lymphotoxin-beta receptor signaling reduces aspects of Sjogren's syndrome in salivary glands of non-obese diabetic mice. Arthritis Res Ther. 2009;11(1):R24.
   PubMed Web of Science ®Google Scholar
• St Clair EW, Baer AN, Wei C, Noaiseh G, Parke A, Coca A, et al. The clinical efficacy and safety of baminercept, a lymphotoxin-beta receptor fusion protein, in primary Sjogren's syndrome: results from a randomized, double-blind, placebo-controlled phase II trial. Arthritis Rheumatol. 2018;70(9):1470–1480.
   PubMed Web of Science ®Google Scholar
• Verstappen GM, Meiners PM, Corneth OBJ, Visser A, Arends S, Abdulahad WH, et al. Attenuation of follicular helper T cell-dependent B cell hyperactivity by abatacept treatment in primary Sjogren's syndrome. Arthritis Rheumatol. 2017;69(9):1850–61.
   PubMed Web of Science ®Google Scholar
• Shinners NP, Carlesso G, Castro I, Hoek KL, Corn RA, Woodland RT, et al. Bruton's tyrosine kinase mediates NF-kappa B activation and B cell survival by B cell-activating factor receptor of the TNF-R family. J Immunol. 2007;179(6):3872–80.
   PubMed Web of Science ®Google Scholar
• Corneth OBJ, Verstappen GMP, Paulissen SMJ, de Bruijn MJW, Rip J, Lukkes M, et al. Enhanced Bruton's tyrosine kinase activity in peripheral blood B lymphocytes from patients with autoimmune disease. Arthritis Rheumatol. 2017;69(6):1313–24.
   PubMed Web of Science ®Google Scholar
• Srinivasan L, Sasaki Y, Calado DP, Zhang B, Paik JH, DePinho RA, et al. PI3 kinase signals BCR-dependent mature B cell survival. Cell 2009;139(3):573–86.
   PubMed Web of Science ®Google Scholar
• Bartok B, Boyle DL, Liu Y, Ren P, Ball ST, Bugbee WD, et al. PI3 kinase δ is a key regulator of synoviocyte function in rheumatoid arthritis. Am J Pathol. 2012;180(5):1906–16.
   PubMed Web of Science ®Google Scholar
• Suarez-Fueyo A, Barber DF, Martinez-Ara J, Zea-Mendoza AC, Carrera AC. Enhanced phosphoinositide 3-kinase delta activity is a frequent event in systemic lupus erythematosus that confers resistance to activation-induced T cell death. J Immunol. 2011;187(5):2376–85.
   PubMed Web of Science ®Google Scholar
• Randis TM, Puri KD, Zhou H, Diacovo TG. Role of PI3Kdelta and PI3Kgamma in inflammatory arthritis and tissue localization of neutrophils. Eur J Immunol. 2008;38(5):1215–24.
   PubMed Web of Science ®Google Scholar
• Suarez-Fueyo A, Rojas JM, Cariaga AE, Garcia E, Steiner BH, Barber DF, et al. Inhibition of PI3Kdelta reduces kidney infiltration by macrophages and ameliorates systemic lupus in the mouse. J Immunol. 2014;193(2):544–54.
   PubMed Web of Science ®Google Scholar
• Grisius MM, Bermudez DK, Fox PC. Salivary and serum interleukin 6 in primary Sjögren's syndrome. J Rheumatol. 1997;24(6):1089–91.
   PubMed Web of Science ®Google Scholar
• Zhou J, Jin JO, Patel ES, Yu Q. Interleukin-6 inhibits apoptosis of exocrine gland tissues under inflammatory conditions. Cytokine. 2015;76(2):244–52.
   PubMed Web of Science ®Google Scholar
• Ishiguro N, Atsumi T, Harigai M, Mimori T, Nishimoto N, Sumida T, et al. Effectiveness and safety of tocilizumab in achieving clinical and functional remission, and sustaining efficacy in biologics-naive patients with rheumatoid arthritis: the FIRST Bio study. Mod Rheumatol. 2017;27(2):217–26.
   PubMed Web of Science ®Google Scholar
• Justet A, Ottaviani S, Dieude P, Taille C. Tocilizumab for refractory organising pneumonia associated with Sjogren's disease. BMJ Case Rep. 2015;2015.
   Google Scholar
• Komai T, Shoda H, Yamaguchi K, Sakurai K, Shibuya M, Kubo K, et al. Neuromyelitis optica spectrum disorder complicated with Sjogren syndrome successfully treated with tocilizumab: A case report. Mod Rheumatol. 2016;26(2):294–6.
   PubMed Web of Science ®Google Scholar
• Ghoreschi K, Laurence A, O'Shea JJ. Janus kinases in immune cell signaling. Immunol Rev. 2009;228(1):273–87.
   PubMed Web of Science ®Google Scholar
• Pertovaara M, Silvennoinen O, Isomäki P. Cytokine-induced STAT1 activation is increased in patients with primary Sjögren's syndrome. Clin Immunol. 2016;165:60–7.
   PubMed Web of Science ®Google Scholar
• Lee J, Lee J, Kwok SK, Baek S, Jang SG, Hong SM. Janus kinase 1 inhibition suppresses interferon-induced B cell activating factor production in human salivary gland: potential therapeutic strategy for primary Sjogren's syndrome. Arthritis Rheumatol 2018.
   Web of Science ®Google Scholar
• van de Veerdonk FL, Lauwerys B, Marijnissen RJ, Timmermans K, Di Padova F, Koenders MI, et al. The anti-CD20 antibody rituximab reduces the Th17 cell response. Arthritis Rheum. 2011;63(6):1507–16.
   PubMedGoogle Scholar
• Ciccia F, Giardina A, Rizzo A, Guggino G, Cipriani P, Carubbi F, et al. Rituximab modulates the expression of IL-22 in the salivary glands of patients with primary Sjogren's syndrome. Ann Rheum Dis. 2013;72(5):782–3.
   PubMed Web of Science ®Google Scholar
• Johnston RJ, Choi YS, Diamond JA, Yang JA, Crotty S. STAT5 is a potent negative regulator of TFH cell differentiation. J Exp Med. 2012;209(2):243–50.
   PubMed Web of Science ®Google Scholar
• Zielinski CE, Mele F, Aschenbrenner D, Jarrossay D, Ronchi F, Gattorno M, et al. Pathogen-induced human TH17 cells produce IFN-γ or IL-10 and are regulated by IL-1β. Nature 2012;484(7395):514–8.
   PubMed Web of Science ®Google Scholar
• Laurence A, Belkaid Y, O'Shea JJ. A degrading view of regulatory T cells. Immunity 2013;39(2):201–3.
   PubMed Web of Science ®Google Scholar
• Luo J, Ming B, Zhang C, Deng X, Li P, Wei Z, et al. IL-2 Inhibition of Th17 generation rather than induction of Treg cells is impaired in primary Sjögren’s syndrome patients. Front Immunol. 2018;9:1755.
   PubMedGoogle Scholar
• Miao M, Hao Z, Guo Y, Zhang X, Zhang S, Luo J, et al. Short-term and low-dose IL-2 therapy restores the Th17/Treg balance in the peripheral blood of patients with primary Sjogren's syndrome. Ann Rheum Dis. 2018;77:1838–40.
   PubMed Web of Science ®Google Scholar
• Adorini L. Interleukin-12, a key cytokine in Th1-mediated autoimmune diseases. Cell Mol Life Sci. 1999;55(12):1610–25.
   PubMed Web of Science ®Google Scholar
• Trinchieri G. Interleukin-12: a cytokine produced by antigen-presenting cells with immunoregulatory functions in the generation of T-helper cells type 1 and cytotoxic lymphocytes. Blood 1994;84(12):4008–27.
   PubMed Web of Science ®Google Scholar
• Stritesky GL, Yeh N, Kaplan MH. IL-23 promotes maintenance but not commitment to the Th17 lineage. J Immunol. 2008;181(9):5948–55.
   PubMed Web of Science ®Google Scholar
• Chimenti MS, Talamonti M, Novelli L, Teoli M, Galluzzo M, Triggianese P, et al. Long-term ustekinumab therapy of psoriasis in patients with coexisting rheumatoid arthritis and Sjogren syndrome. Report of two cases and review of literature. J Dermatol Case Rep. 2015;9(3):71–5.
   PubMed Web of Science ®Google Scholar
• Ivanov II, McKenzie BS, Zhou L, Tadokoro CE, Lepelley A, Lafaille JJ, et al. The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell 2006;126(6):1121–33.
   PubMed Web of Science ®Google Scholar
• Manel N, Unutmaz D, Littman DR. The differentiation of human T(H)-17 cells requires transforming growth factor-beta and induction of the nuclear receptor RORgammat. Nat Immunol. 2008;9(6):641–9.
   PubMed Web of Science ®Google Scholar
• Iizuka M, Tsuboi H, Matsuo N, Asashima H, Hirota T, Kondo Y, et al. A crucial role of RORγt in the development of spontaneous Sialadenitis-like Sjögren's syndrome. J Immunol. 2015;194(1):56–67.
   PubMed Web of Science ®Google Scholar
• Tahara M, Tsuboi H, Segawa S, Asashima H, Iizuka-Koga M, Hirota T, et al. RORgammat antagonist suppresses M3 muscarinic acetylcholine receptor-induced Sjogren's syndrome-like sialadenitis. Clin Exp Immunol. 2017;187(2):213–24.
   PubMed Web of Science ®Google Scholar
• Armant M, Avice MN, Hermann P, Rubio M, Kiniwa M, Delespesse G, et al. CD47 ligation selectively downregulates human interleukin 12 production. J Exp Med. 1999;190(8):1175–82.
   PubMed Web of Science ®Google Scholar
• Masli S, Turpie B, Streilein JW. Thrombospondin orchestrates the tolerance-promoting properties of TGFbeta-treated antigen-presenting cells. Int Immunol. 2006;18(5):689–99.
   PubMed Web of Science ®Google Scholar
• Turpie B, Yoshimura T, Gulati A, Rios JD, Dartt DA, Masli S. Sjögren's syndrome-like ocular surface disease in thrombospondin-1 deficient mice. Am J Pathol. 2009;175(3):1136–47.
   PubMed Web of Science ®Google Scholar
• Contreras Ruiz L, Mir FA, Turpie B, Masli S. Thrombospondin-derived peptide attenuates Sjogren's syndrome-associated ocular surface inflammation in mice. Clin Exp Immunol. 2017;188(1):86–95.
   PubMed Web of Science ®Google Scholar
• Sthoeger Z, Sharabi A, Asher I, Zinger H, Segal R, Shearer G, et al. The tolerogenic peptide hCDR1 immunomodulates cytokine and regulatory molecule gene expression in blood mononuclear cells of primary Sjogren's syndrome patients. Clin Immunol. 2018;192:85–91.
   PubMed Web of Science ®Google Scholar
• Gottenberg JE, Ravaud P, Puechal 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(3):249–58.
   PubMed Web of Science ®Google Scholar
• Burge DJ, Eisenman J, Byrnes-Blake K, Smolak P, Lau K, Cohen SB, et al. Safety, pharmacokinetics, and pharmacodynamics of RSLV-132, an RNase-Fc fusion protein in systemic lupus erythematosus: a randomized, double-blind, placebo-controlled study. Lupus. 2017;26(8):825–34.
   PubMed Web of Science ®Google Scholar
• Shi GP, Villadangos JA, Dranoff G, Small C, Gu L, Haley KJ, et al. Cathepsin S required for normal MHC class II peptide loading and germinal center development. Immunity 1999;10(2):197–206.
   PubMed Web of Science ®Google Scholar
• Li X, Wu K, Edman M, Schenke-Layland K, MacVeigh-Aloni M, Janga SR, et al. Increased expression of cathepsins and obesity-induced proinflammatory cytokines in lacrimal glands of male NOD mouse. Invest Ophthalmol Vis Sci. 2010;51(10):5019–29.
   PubMed Web of Science ®Google Scholar
• Hamm-Alvarez SF, Janga SR, Edman MC, Madrigal S, Shah M, Frousiakis SE, et al. Tear cathepsin S as a candidate biomarker for Sjogren's syndrome. Arthritis Rheumatol. 2014;66(7):1872–81.
   PubMed Web of Science ®Google Scholar
• Baum BJ, Alevizos I, Zheng C, Cotrim AP, Liu S, McCullagh L, et al. Early responses to adenoviral-mediated transfer of the aquaporin-1 cDNA for radiation-induced salivary hypofunction. Proc Natl Acad Sci USA. 2012;109(47):19403–7.
   PubMed Web of Science ®Google Scholar
• Alevizos I, Zheng C, Cotrim AP, Liu S, McCullagh L, Billings ME, et al. Late responses to adenoviral-mediated transfer of the aquaporin-1 gene for radiation-induced salivary hypofunction. Gene Ther. 2017;24(3):176–86.
   PubMed Web of Science ®Google Scholar
• Yin H, Cabrera-Perez J, Lai Z, Michael D, Weller M, Swaim WD, et al. Association of bone morphogenetic protein 6 with exocrine gland dysfunction in patients with Sjogren's syndrome and in mice. Arthritis Rheum. 2013;65(12):3228–38.
   PubMed Web of Science ®Google Scholar
• Lai Z, Yin H, Cabrera-Perez J, Guimaro MC, Afione S, Michael DG, et al. Aquaporin gene therapy corrects Sjogren's syndrome phenotype in mice. Proc Natl Acad Sci USA. 2016;113(20):5694–9.
   PubMed Web of Science ®Google Scholar
• Yin H, Nguyen CQ, Samuni Y, Uede T, Peck AB, Chiorini JA. Local delivery of AAV2-CTLA4IgG decreases sialadenitis and improves gland function in the C57BL/6.NOD-Aec1Aec2 mouse model of Sjogren's syndrome. Arthritis Res Ther. 2012;14(1):R40.
   PubMed Web of Science ®Google Scholar
• Nguyen CQ, Yin H, Lee BH, Chiorini JA, Peck AB. IL17: potential therapeutic target in Sjogren's syndrome using adenovirus-mediated gene transfer. Lab Invest. 2011;91(1):54–62.
   PubMed Web of Science ®Google Scholar
• Kok MR, Yamano S, Lodde BM, Wang J, Couwenhoven RI, Yakar S, et al. Local adeno-associated virus-mediated interleukin 10 gene transfer has disease-modifying effects in a murine model of Sjogren's syndrome. Hum Gene Ther. 2003;14(17):1605–18.
   PubMed Web of Science ®Google Scholar
• Lee BH, Carcamo WC, Chiorini JA, Peck AB, Nguyen CQ. Gene therapy using IL-27 ameliorates Sjogren's syndrome-like autoimmune exocrinopathy. Arthritis Res Ther. 2012;14(4):R172.
   PubMed Web of Science ®Google Scholar
• Xu J, Su Y, Hu L, Cain A, Gu Y, Liu B, et al. Effect of bone morphogenetic protein 6 on immunomodulatory functions of salivary gland-derived mesenchymal stem cells in Sjogren's Syndrome. Stem Cells Dev. 2018;27(22):1540–1548.
   PubMed Web of Science ®Google Scholar
• Yin H, Kalra L, Karim A, Lai Z, Guimaro M, Aber L, et al. Bone morphogenetic protein 6 receptor inhibition restores salivary gland function in a mouse model of primary Sjögren’s syndrome [abstract]. Arthritis Rheumatol. 2016;68(suppl 10).
   PubMedGoogle Scholar
• Zeng M, Szymczak M, Ahuja M, Zheng C, Yin H, Swaim W, et al. Restoration of CFTR activity in ducts rescues acinar cell function and reduces inflammation in pancreatic and salivary glands of mice. Gastroenterology 2017;153(4):1148–59.
   PubMed Web of Science ®Google Scholar