ANALYSIS OF B CELL SUBSETS AND B CELL CYTOKINES IN PEDIATRIC SJOGREN’S SYNDROME

R. Nicolai, C. Bracaglia, A. Boni, I. Caiello, D. Pires Marafon, F. De Benedetti, E. MarascoBambino Gesu’ Children Hospital, Unit of Rheumatology, Rome, Italy  Background Pediatric Sjögren’s syndrome (pSS) is a rare disorder that is often diagnosed late due to the lack of validated diagnostic criteria and validated biomarkers. The pathogenesis is largely unknown, but there is evidence of involvement of both the innate and adaptive branch of the immune system. Immunological overactivity is central in the pathogenesis of pSS. Several studies showed the presence of B cells abnormalities in patients with SS with an expansion of naïve B cells and a decrease in the frequency of memory B cells. Objectives We set out to investigate the distribution of B cell subsets and B cell cytokines in patients with pSS at disease onset and at follow up visits. Methods A monocentric retrospective cohort study was conducted on 23 patients with pSS enrolled at the department of Rheumatology of Bambino Gesù Children’s Hospital. Serum levels of CXCL13 and BAFF were analyzed by ELISA. B cell phenotype was assessed on peripheral blood mononuclear cells (PBMCs) by flow cytometry. Systemic disease activity was evaluated by ESSDAI (EULAR Sjogren’s syndrome disease activity index) and Clinical-ESSDAI score (Clin-ESSDAI), according to 2020 EULAR recommendations; active disease was defined by ClinESSDAI ≥1 and remission by ClinESSDAI=0. As controls we selected age-matched people with no diagnosis of pSS or any other systemic autoimmune disease. Results Serum levels of CXCL13 and BAFF were significantly higher in patients with pSS than the control group (p<0.05) (Figure 1A). We correlated levels of biomarkers with clinical and laboratory parameters: we observed a positive correlation between hypergammaglobulinemia and BAFF (rho=+0,80). Analysis of B-cell subsets at disease onset revealed the expansion of a population of atypical memory B cells (p=0,00049) and a reduction in lgM memory B cells (p=0,0034) compared to the control group (Figure 1B). We then compared the distribution of B cell subpopulations at disease onset (pre) with samples obtained at follow-up (post) for each patient no significant differences were observed (Figure 1B). We also investigated the distribution of Tfh cells in patients with pSS and we observed a significant expansion of CXCR5-PD1 Tfh (Figure 1B). Conclusion Patients with pSS showed high levels of CXCL13 and BAFF at disease onset. Alteration in B cell subsets are present in patients with pSS compared to controls, with an expansion of atypical memory B cells and Tfh. The B cell abnormalities are not affected by treatment. Our data confirm an hyperactivation of the humoral immune system in patients with pSS and provide evidence for their development as biomarkers and to develop new therapeutic strategies aimed at controlling B cell hyperactivation in pediatric patients with SS. Figure 1. Image/graph: REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests None Declared. Keywords: Sjögren syndrome, Cell biology, Adaptive immunity DOI: 10.1136/annrheumdis-2023-eular.4075Citation: , volume 82, supplement 1, year 2023, page 21Session: Improving our understanding of RMDs in children and young people (Oral Presentations)