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POS0453 EXPLORATORY IMMUNOPHENOTYPE OF THE RARE DISEASE JUVENILE SJÖGREN’S SYNDROME REVEALS A DYSREGULATION OF B AND T MEMORY CELL FREQUENCIES
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  1. L. Martin-Gutierrez1,
  2. H. Peckham2,
  3. A. Radziszewska2,
  4. J. Peng2,
  5. O. Nette2,
  6. E. Jury1,
  7. C. Ciurtin2
  1. 1University College London, Centre for Rheumatology Research, London, United Kingdom
  2. 2University College London, Centre for Adolescent Rheumatology Versus Arthritis, London, United Kingdom

Abstract

Background Sjögren’s syndrome (SS) is an autoimmune rheumatic disease characterised by dryness resulting from chronic lymphocytic infiltration of the exocrine glands. Patients also present with other extraglandular manifestations such as arthritis, anemia and fatigue or various organ and systems involvement. The disease is more frequent in women aged 30-50. However, in rare cases, the disease starts in childhood and is known as juvenile SS (JSS) or childhood SS. Children have different clinical manifestations compared to adults, with dryness being less common, making the diagnosis very challenging1.

Objectives To investigate in depth the immune cell profile of patients with JSS for better understanding of disease pathogenesis.

Methods Peripheral blood was collected from a cohort of patients with JSS while attending appointments at UCLH clinics. None had received B-cell depletion therapy. Immune-phenotyping of 29 immune-cell subsets, including B and T cells, in peripheral blood from patients with JSS (n=10) and age and sex-matched healthy controls (n=10) was performed using flow cytometry as we have performed previously for patients with adult onset SS2. Data were analysed using multiple t-tests and compared with the adult SS immune phenotype.

Results Patients with JSS had an average age of 18 years (range 16-21) with an average age of disease onset at 14 years (range 12-18). Up to 60% of patients presented Anti-Ro autoantibodies while 50% presented Anti-La autoantibodies.

Patients with JSS had an altered immune profile compared to age matched healthy controls (average of 18 years, range 15-25). In the B cell compartment, JSS patients had higher frequencies of Total CD19+ B cells (p=0.0044), Naïve B cells (CD19+IgD+CD27-) (p=0.0183) and bm2 (CD19+IgD+CD38+) (p=0.0490) whereas memory B cell subsets such as early bm5 (CD19+IgD-CD38+) and late bm5 (CD19+IgD-CD38-) were significantly reduced (p=0.0249, and p=0.0117 respectively), similar to the profile seen in patients with adult-SS. Interestingly, in the CD4+ T cell compartment, central memory (CD4+CD27+CD45RA-) T cells were significantly reduced (p=<0,0001) but effector memory (CD4+CD27-CD45-) and effector memory-re-expressing-CD45RA (EMRA, CD4+CD27-CD45RA+) T-cell subsets were significantly elevated (p=0.0171 and p=0.0002 respectively). These changes were not identified in adult-SS patients. Finally, unlike our observations in patients with adult-onset SS there was no widespread deregulation of CD8+ T cell subsets in JSS patients; only a significant increase in CD8+CD25-CD127+ responders T cells (p=0.0392) was observed in JSS patients versus healthy.

Conclusion This is the first pilot study investigating the immunophenotype profile of patients with JSS. Our preliminary findings suggest altered immune phenotypes in both B-cell and T cell compartments and for B cells are in concordance with previous immunophenotyping studies in adult SS (predominance of naïve and lower frequencies of memory B cells), suggesting an immunological rationale for the use of similar therapies. Further studies, comparing the adult with the juvenile phenotype could help stratify patients for targetted therapies and improve treatment in this rare disease in children for which no evidence-based recommnedations exist.

References [1]Ciurtin C et al. Barriers to translational research in Sjögren’s syndrome with childhood onset: challenges of recognising and diagnosing an orphan rheumatic disease. Lancet Rheumatology. 2021; https://doi.org/10.1016/S2665-9913(20)30393-3.

[2]Martin-Gutierrez L, Peng J, et al. Stratification of Patients with Sjogren’s Syndrome and Patients With Systemic Lupus Erythematosus According to Two Shared Immune Cell Signatures, With Potential Therapeutic Implications. Arthritis Rheumatol. 2021;73(9):1626-37.

Disclosure of Interests None declared.

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