Introduction
Arthritis is a common manifestation in systemic lupus erythematosus (SLE), observed in up to 90% of patients 1. It often occurs at disease onset and is part of classification criteria2, 3, but it is usually non-erosive, although advanced imaging has revealed that chronic synovitis 4 and erosions 5 are more common than previously estimated.
Despite being frequent and causing a significant disease burden by influencing quality of life 6, arthritis has received less attention than other SLE manifestations, such as nephritis, that directly impact morbidity and survival. While several studies have investigated possible associations of arthritis with genetic risk factors, immunological features, and autoantibodies 6, little is known of the local inflammatory cell phenotypes and cytokines.
In the 70ties and 90ties, descriptive studies of SLE synovial biopsies have demonstrated microvascular changes, moderate proliferation of the synovial lining layer as well as mononuclear cell infiltrates and fibrin deposits7 in affected tissue. The synovial fluid was found to typically contain less than 2000 leucocytes per microliter, and to be characterized by lymphocytes and so called lupus erythematosus (LE) cells, i.e. the presence of nucleic acids in the cytoplasm of neutrophils and macrophages8. Presence of anti-nuclear antibodies (ANA) were also reported in synovial fluid of SLE patients9. In 2007, Toukap N et al.10 analyzed the gene expression of synovial biopsies and found that SLE patients display a distinct molecular signature, with up-regulation of interferon inducible genes and down-regulation of genes involved in extracellular matrix homeostasis. However, the involvement of specific cell types or cytokines in lupus arthritis still remains unknown.
In order to better understand SLE joint pathology, we analyzed cytokines associated to T-cell responses and the cellular composition (when present) of synovial fluid (SF) samples from SLE patients as compared to paired peripheral blood samples and found an upregulation of IL-6 and IL-17A in synovial fluid of SLE patients, as well as potential pathogenic T cell subsets.