Abstract
Background: Musculoskeletal involvement is a common clinical feature of systemic lupus erythematosus (SLE), that can be present either at the onset or in later disease course. SLE related arthritis is usually non-erosive and non-deforming as opposed to rheumatoid arthritis (RA). While RA synovial pathology has been extensively studied, little is known about the pathophysiology of arthritis in SLE. Objectives: to explore the cellular compartments in synovial fluid of SLE patients with arthritic manifestations. Methods: paired synovial fluid (SF) samples from large joint aspiration and peripheral blood samples (PBMC) obtained at the same time point from five SLE patients were analyzed by multicolor flow cytometry. The patients fulfilled the ACR 1982 classification criteria for SLE [1]. Clinical records were reviewed in order to exclude the presence of comorbidities such osteoarthritis or overlap with RA. Three different lineage-specific panels for B cells, T cells (cytotoxic and helper) were developed. Results: The overall frequency of CD4+ and CD8+ T cells was similar across the SF and PBMC samples. Among the CD4+ T cells, those co-expressing CCR4, showed a much higher frequency in the SF compared to the peripheral blood in 4 out of 5 patients (mean percentage 8.9±7.0% vs 2.1±1.6%, p=ns). In addition, in 4 out of 5 patients we could identify an increased frequency of CD4+ expressing CCR6+, a marker for Th17 cells in SF as compared to PBMC (mean percentage 35±16.6% vs 12.7±8.9%, respectively, p=ns). In all patients, a higher frequency of EOMES+ Granzyme A + CD4+ T cells was observed in SF when compared to PBMC (9.2±2.5% vs 4.5±2.5%, p=0.03). Moreover, in all patients, we could observe a higher proportion of regulatory T cells (FOXP3+/CD25+) in the SF (21.5±15.4% vs 8.4±7.8%, p=ns). No relevant differences were observed in the Th1 compartment (CXCR3+). CD19+ cells (B-lymphocytes) were scarcely present in the SF of SLE patients as opposed to the peripheral blood. Conclusion: Although SLE is usually considered to be a B cell driven disease, its common clinical features like arthritis could be driven in situ by T cells, namely subtypes of CD4+ (helper) cells such as TH17 cells and CD4+ T cells with cytotoxic profile. Further confirmation of the present findings is needed. Reference [1] Tan, E.M., et al., The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum, 1982. 25(11 Disclosure of Interests: Francesca Faustini Consultant for: I have participated to an advisoryborad for Pfizer Sweden in one occasion during 2018, Speakers bureau: I have been speaker for an internal education meeting for Novartis Sweden in one occasion during 2018, Natalie Sippl: None declared, Karine Chemin: None declared, Iva Gunnarsson: None declared, Vivianne Malmstrom: None declared
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