Complex immunophenotyping stratifies patients with primary and secondary Sjögren’s syndrome into distinct clinically relevant groups with potential therapeutic implications

Sjögren’s syndrome (SS) and systemic lupus erythematosus (SLE) are distinct autoimmune rheumatic diseases (ARD) characterised by shared clinical features and immune abnormalities. A proportion of 15-20% of patients with SLE also have features of SS, manifesting as an overlap ARD called secondary SS associated with SLE (SS/SLE). Both SLE and SS are B cell driven diseases, with a recognised female predominance. SS is characterised by distinctive chronic inflammatory process leading to destruction of the exocrine glands orchestrated by T and B lymphocytes, dendritic cells (DCs), macrophages and other mononuclear cells. These cells have been demonstrated to also play a role in SLE and SS pathogenesis, while the immune phenotype of SS/SLE patients has not been investigated before. The results of my research demonstrated that the clinical, serological and histological parameters used by clinicians in routine practice have not been able to distinguish between patients with different diagnoses when stratified using unsupervised hierarchical clustering. However, in-depth immune phenotype have found that these patients also had both unique and shared defects in their CD19+ B cells, CD4+ and CD8+ T cells peripheral blood profiles, as well as defects in lipid raft expressions in these cell subsets, as assessed by flow-cytometry and ImageStream analyses. Overall, in-depth immune phenotyping was able to stratify pSS, SLE and SS/SLE with common underlying B and T cell abnormalities based on their immune signatures rather than diagnosis, which can have significant therapeutic implications in the selection of treatment strategies