OA11 Juvenile Sjögren’s syndrome is characterised by dysregulated of B and T memory cell frequencies: a pilot immunophenotyping analysis of this rare disease phenotype
Authors: Martin-Gutierrez Lucia , Peckham Hannah , Radziszewska Anna , Peng Junjie , Nettey Oluwatomisin , Jury Elizabeth , Ciurtin Coziana 
Published: April 2023

Abstract

Background/Aims
Sjögren’s syndrome (SS) is an autoimmune rheumatic disease characterised by dryness resulting from chronic lymphocytic infiltration of the exocrine glands and extra glandular manifestations such as arthritis, anemia, and fatigue. The disease is more frequent in women aged 30-50. However, in rare cases, the disease starts in childhood, known as juvenile SS (jSS). Children have different clinical manifestations compared to adults, with dryness being less common, making the diagnosis very challenging. Our aim is to investigate in depth the immune cell profile of patients with jSS and their cytokine profile for better understanding of disease pathogenesis.

Methods
Peripheral blood was collected from a cohort of patients with jSS (n = 10) and age and sex-matched healthy controls (HC) (n = 10). None of the patients had received B-cell depletion therapy. Peripheral blood immune-phenotyping of 29 immune-cell subsets, including B and T cells, was performed using flow cytometry as we have reported previously for patients with adult-onset SS. Data were analyzed using multiple t-tests and compared with the adult SS immune phenotype. A panel of 15 serum cytokines associated with SS pathology were measured by Luminex, multiple t-tests were performed to detect statistically significant differences between jSS and HCs.

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). 60% of patients had anti-Ro autoantibodies and 50% had anti-La autoantibodies. Patients with jSS had an altered immune profile compared to age-matched healthy controls (HCs) (mean age = 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). Interestingly, in the CD4+ T cell compartment, central memory T cells (CD4+CD27+CD45RA-) were significantly reduced (p = &lt;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). There was also a significant increase in CD8+CD25-CD127+ responders T cells (p = 0.0392) in jSS patients versus HCs. Serum cytokines levels of APRIL and CCL8 were significantly elevated in jSS.

Conclusion
This is the first pilot study investigating the immune profile of patients with jSS. In line with our previous studies in adults we detected elevated naïve and reduced frequencies of memory B cells, suggesting an immunological rationale for the use of similar therapies across age. However, we also found a specific dysregulation of the responder CD8+ T cell subpopulation in jSS versus HCs, which requires further investigation. Our cytokine data could indicate an ongoing dysregulation of the homeostasis of mature B-cells and activation of different immune cells.
Disclosure
L. Martin-Gutierrez: None. H. Peckham: None. A. Radziszewska: None. J. Peng: None. O. Nettey: None. E. Jury: None. C. Ciurtin: None.