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.