THU0208 EBV SEROLOGICAL PROFILE AFFECTS CIRCULATING LYMPHOCYTES IN PSS

Background Genetic, hormonal, and environmental triggers have been related to the dysregulated autoimmune response observed in primary Sjogren Syndrome (pSS), but its aetiology is still unestablished. Epstein-Barr virus (EBV) is a strong candidate as a trigger for the autoimmune epithelitis in pSS. Objectives We aimed to evaluate the EBV serology in pSS patients, and to compare it with other autoimmune patients and healthy controls (HC). In parallel, we have characterized the immune profile of pSS patients, in order to assess if the viral background affects the circulating lymphocytes. Methods We have recruited 34 pSS patients (2002 AECG criteria), 20 Rheumatoid arthritis (RA) patients (ACR/EULAR classification criteria) and 20 HC. Immunoenzymatic assays were used to determine the serum levels of IgG, IgA and IgM antibodies against EBV Nuclear Antigen (EBNA), Early Antigen (EA) and Capside antigen (VCA). Flow cytometry was used for the characterization of T and B cells, including regulatory (Tregs) and follicular (Tfh) T cells, T helper and Bm1-Bm5 subsets. Significance was considered for p Results All sera were negative for VCA-IgM. Only 2 HC and 3 RA were positive for EA-IgA. For VCA-IgG and EBNA-IgG we found no differences in positive cases between groups (all participants, except 2 pSS were positive for VCA-IgG; 26/34 pSS, 16/20 RA and 13/20 HC were positive for EBNA-IgG). However, pSS patients evidenced more positive sera for EA-IgG than HC (32% vs 5%; p=0.0215) and RA (32% vs 20%; p=0.2312), suggesting a more prevalent state of late acute/chronic active infection in pSS. Thus, according to the serologic pattern observed, we divided pSS patients in 3 groups: G1 (n=18), past infection (EA-IgG–, EBNA IgG+); G2 (n=11), late acute/chronic active infection (EA IgG+, EBNA IgG+/-), and G3 (n=5), without serological evidence of active infection (EA IgG–, EBNA IgG–). Within the T cell compartment, G2 patients presented increased percentages Tregs compared to G1 pSS patients (p=0.031). G1 and G2 patients presented increased CXCR3+ Th1 cells and CXCR3+ Tfh1 compared to G3 (Th1: G1vsG3, p=0.120 and G2vsG3, p=0.008; Tfh1: G1vsG3, p=0.003 and G2vsG3, p=0.067). As for B cells, pSS patients are known to have increased percentages of transitional Bm2’ cells in circulation, and in fact we found that these cells were also augmented in G2 patients compared to G1 (p=0.024). Moreover, plasmablasts (Bm3+Bm4) were increased in G1 and G2 patients compared to G3 (%, G1vsG3, p=0.088 and G2vsG3, p=0.003; absolute counts, G1vsG3, p=0.020 and G2vsG3, p=0.003). Plasmablasts were also slightly augmented in G2 patients compared to G1 (p=0.099). Conclusion Our study shows a higher prevalence of EA-IgG in pSS patients. Moreover, the distinct EBV serological profiles observed in pSS patients seem to affect circulating B and T cells. Particularly, pSS patients with serological evidence for late acute/chronic active infection show a more proinflammatory pattern, with increased Th1 cells, and elevated transitional B cells with increased plasmablast differentiation. Despite the low number of cases and the absence of other confirmatory methodologies, our study reveals for the first time the association of EBV with distinct immune profile in pSS patients. Disclosure of Interests Filipe Barcelos Consultant for: Pfizer; Ely-Lilly, Speakers bureau: Novartis, Catarina Martins: None declared, Ricardo Monteiro: None declared, Tiziano Prussiani: None declared, Miguel Sitima: None declared, Jose Vaz-Patto: None declared, Jaime Branco: None declared, Luis Miguel Borrego Grant/research support from: MSD, Consultant for: MSD; Tecnifar, Paid instructor for: MSD; AstraZeneca, Speakers bureau: MSD; Tecnifar; AstraZeneca