S-47 Clinical and Experimental Rheumatology 2018 1 Faculty of Medicine and Life Sciences, University of Tampere; 2 BioMediTech, Tampere; 3 Fimlab Laboratories, Tampere; 4 Department of Internal Medicine, Centre for Rheumatic Diseases, Tampere University Hospital; 5 Faculty of Medicine and Life Sciences, University of Tampere; 6 Department of Dermatology, Tampere University Hospital, Tampere, Finland. Noora Ranta*, Medical student Atte Valli*, Medical student Anna Grönholm, PhD Olli Silvennoinen, MD, PhD Pia Isomäki, MD, PhD Marko Pesu # , MD, PhD Marja Pertovaara # , MD, PhD *N. Ranta and A. Valli contributed equally to this work. # M. Pesu and M. Pertovaara contributed equally to this work. Please address correspondence to: Dr Marja Pertovaara, Department of Internal Medicine, Centre for Rheumatic Diseases, Tampere University Hospital, P.O. Box 2000, FI-33521 Tampere, Finland. E-mail: marja.pertovaara@fmnet.f Received on November 17, 2017; accepted in revised form on February 1, 2018. Clin Exp Rheumatol 2018; 36 (Suppl. 112): S47-S50. © Copyright CLINICAL AND EXPERIMENTAL RHEUMATOLOGY 2018. Key words: biomarker, Sjögren’s syndrome, proprotein convertase, )85,1 LQWHUIHURQƢ Funding: this work was supported by the Academy of Finland (grants 295814 and 286477), the Competitive State Research Financing of the Expert Responsibility area of Tampere University Hospital (Grants 9U047 and 9V049), the Tampere Tuberculosis Foundation, the Sigrid Juselius Foundation, the Finnish Cultural Foundation Pirkanmaa Regional fund and the Cancer Society of Finland. Competing interests: none declared. ABSTRACT Objective. The proprotein convertase enzyme FURIN is a critical regulator of the anti-infammatory TGFβ-1 cytokine and peripheral immune tolerance. In T cells, FURIN is co-regulated with IFN-γ and thus highly expressed in T helper 1 type cells. Previous studies have demonstrated that FURIN is up- regulated in infammatory conditions, including atherosclerosis, rheumatoid arthritis and systemic lupus erythema- tosus. Here, we evaluated the levels of FURIN in the plasma and peripheral blood mononuclear cells (PBMCs) of patients with primary Sjögren’s syn- drome (pSS) and in healthy controls. Methods. FURIN plasma levels were determined by ELISA, and the mRNA expression in PBMCs was quantitated using qPCR. FURIN levels in the plas- ma were correlated with the clinical and demographic characteristics of the patients. Results. FURIN was found to be sig- nifcantly upregulated at both the pro- tein and mRNA level in pSS patients compared to healthy controls. In pSS patients, high FURIN protein levels were signifcantly associated with el- evated IFN-γ levels in the plasma as well as a longer duration of sicca symptoms in the eyes. pSS patients with high FURIN levels in their plasma showed a trend towards lower levels of serum beta-2 microglobulin, ESR and a lower systemic disease activity index ESSDAI. Conclusion. The proprotein con- vertase FURIN is signifcantly upregu- lated in pSS. Elevated FURIN levels associate with high levels of the Th1 type cytokine IFN-γ and long dura- tion of dry eye symptoms. Patients with high FURIN levels show signs of lower disease activity suggesting that FURIN might have a protective role in pSS. Introduction Primary Sjögren’s syndrome (pSS) is a chronic systemic autoimmune disease FKDUDFWHULVHG E\ O\PSKRF\WLF LQﾀOWUD- tion in the salivary and lacrimal glands and over-activation of B cells leading subsequently to hypergammaglobuli- naemia and development of autoan- tibodies (1, 2). According to current knowledge, the main pathophysiologi- cal mechanisms in pSS are mediated through the interferon (IFN) I and IFN II pathways (1, 2). The type II cytokine ,)1Ƣ KDV EHHQ IRXQG WR EH UHVSRQVLEOH for the gland dysfunctions in Ro/SSA immunised mice. Vice versa, a reduc- WLRQ LQ WKH OHYHO RI ,)1Ƣ RU ,)1Ƣ5 seems to inhibit the development of pSS (2). The proprotein convertase subtilisin/ kexin enzymes (PCSKs) activate vari- ous immature proteins by catalysing WKHLU SRVWWUDQVODWLRQDO VLWHVSHFLﾀF K\- drolytic cleavage (3). The ubiquitously expressed PCSK enzyme FURIN catal- yses the proteolysis of a large number of substrates with immunoregulatory func- tions including cytokines, integrins and viral envelope proteins (3-5). FURIN is upregulated in Th1 cells via the IL-12/ Stat4 pathway (6). The T-cell-expressed FURIN regulates Th cell polarisation and peripheral immune tolerance by controlling the functional maturation of WUDQVIRUPLQJ JURZWK IDFWRU EHWD 7*)ơ 1) (3, 6, 7). FURIN is also upregulated LQ FKURQLF DXWRLPPXQH LQﾁDPPDWLRQ DV is seen in patients with rheumatoid ar- thritis (RA) (8) and systemic lupus ery- thematous (SLE) (9). The fact that FURIN is an important regulator of peripheral immune toler- ance and highly expressed in Th1-type lymphocytes prompted us to determine the levels of the FURIN protein and mRNA in patients with pSS compared to healthy controls. Proprotein convertase enzyme FURIN is upregulated in primary Sjögren’s syndrome N. Ranta 1,2 , A. Valli 1 , A. Grönholm 1,2 , O. Silvennoinen 1,3 , P. Isomäki 4,5 , M. Pesu 2,5,6 , M. Pertovaara 4,5