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Lupus and Sjögren’s syndrome distinct disease endotypes clustered based on activity scores and immune profiles

Thompson, NL; Gandhi,, A; Radmore, R; Gupta, V; Robinson, G; Cho, S; Isenberg, DA; ... Ciurtin, C; + view all (2017) Lupus and Sjögren’s syndrome distinct disease endotypes clustered based on activity scores and immune profiles. Presented at: UCL DoM Research Retreat, London, United Kingdom. Green open access

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Abstract

Background: Sjögren’s syndrome (SS) is a chronic autoimmune disorder affecting approximately 0.1–0.4% of the general population with a female-to-male ratio of 9:1 usually diagnosed in the fourth and fifth decades of life [1]. Clinically, SS is typified by ocular and oral dryness developed as a consequence of the autoimmune process. It may occur either alone, as primary (p)SS, or secondary to other autoimmune disease, often rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) or systemic sclerosis, secondary (s)SS. Objectives: 1) Identify the peripheral B and T cells abnormalities in patients with pSS, secondary SS associated with systemic lupus erythematosus (SLE) and SLE alone in comparison to healthy donors. 2) Correlate immune phenotypes with clinical features and serological parameters. 3) Identify distinct patients’ endotypes relevant for therapeutic strategies. Methods: Blood samples, clinical and laboratory parameters from 28 patients with pSS, 32 SLE, 15 SS/SLE and age/sex-matched HC were obtained. Immunophenotyping and lipid-raft analyses were performed by flow-cytometry. Results: There were distinct CD19+ B cells, and CD4+ and CD8+ T cell subpopulations observed in pSS, SLE and SS/SLE patients compared to healthy donors. SS/SLE have the most striking B cell phenotype abnormalities than patients with pSS or SLE (increased Bm2 cells and decreased early and late Bm5 cells).There were significant positive and negative correlations of immune cells with clinical parameters in pSS, SLE and SS/SLE patients. The fold-change of memory B cells was significantly reduced in all disease groups with comparison to healthy controls. Fold-change of CD8+ T responder cells were significantly reduced in all diseases, and similarly, CD4+ naïve T cells in SLE and SS/SLE. A highly significant increase in CD4+ T regulatory was observed in pSS. Hierarchical clustering of immune cells in patients yielded 5 distinct endotypes, with clustering reflected in patients with similar disease activity scores. Conclusions: This is the first comprehensive immunophenotype analysis performed patients with pSS, SLE and SS/SLE. We identified significant reduction in memory B cells fold-changed in all disease groups, reduction in CD4+ naïve T cells in SLE and SS/SLE and reduction in T responders in all disease CD8+ in comparison to healthy donors. The most significant T cell abnormalities were found in patients with SLE, however a significant correlation between lipid raft expression as marker of cell activation and disease activity score (ESSDAI) was found only in pSS patients. The five distinct disease endotype clustering showed distinct immune profile in patients with overlapping autoimmune conditions which is particularly relevant for stratification of therapy.

Type: Poster
Title: Lupus and Sjögren’s syndrome distinct disease endotypes clustered based on activity scores and immune profiles
Event: UCL DoM Research Retreat
Location: London, United Kingdom
Open access status: An open access version is available from UCL Discovery
Language: English
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation
URI: https://discovery.ucl.ac.uk/id/eprint/1555758
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