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Arthritis in systemic lupus erythematosus is characterized by local IL-17A and IL-6 expression
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  • Natalie Sippl,
  • Francesca Faustini,
  • Johan Rönnelid,
  • Sara Turcinov,
  • Karine Chemin,
  • Iva Gunnarsson,
  • V Malmström
Natalie Sippl
Karolinska Institute
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Francesca Faustini
Karolinska Institute
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Johan Rönnelid
Uppsala University
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Sara Turcinov
Karolinska Institute
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Karine Chemin
Karolinska Institute
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Iva Gunnarsson
Karolinska Institute
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V Malmström
Karolinska Institute
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Abstract

Arthritis is a common clinical feature of systemic lupus erythematosus (SLE) and is usually non-erosive as opposed to rheumatoid arthritis (RA). While RA synovial pathology has been extensively studied, little is known about the pathophysiology of lupus arthritis. Here, we aimed to explore the cytokine and cellular compartments in synovial fluids of SLE patients with arthritic manifestations. Acellular synovial fluid and paired serum samples from SLE patients (n=17) were analyzed with cytokine bead array for T helper associated cytokines. From two SLE patients, synovial fluid mononuclear cells (SFMC) were analyzed by multiparameter flow cytometry to dissect T cell, B cell, monocyte and dendritic cell phenotypes. SLE-derived SFMC were further stimulated in vitro to measure their capacity for producing IFN and IL-17A. All patients fulfilled the ACR 1982 classification criteria for SLE. Clinical records were reviewed to exclude the presence of comorbidities such as osteoarthritis or overlap with RA. IL-17A and IL-6 levels were high in SLE synovial fluid. A clear subset of the synovial CD4+ T cells expressed CCR6+, a marker associated with Th17 cells. IL-17-production was validated amongst CD4+CCR6+ T cells following in vitro stimulation. Furthermore, a strong IFN production was observed in both CD4+ and CD8+ cells. Our study shows high IL-17A and IL-6 levels in synovial fluids of patients with lupus arthritis. The Th17 pathway have been implicated in several aspects of SLE disease pathogenesis and our data points to Th17 involvement also for lupus arthritis.

Peer review status:ACCEPTED

08 Jan 2021Submitted to Clinical & Experimental Immunology
12 Jan 2021Submission Checks Completed
12 Jan 2021Assigned to Editor
12 Jan 2021Reviewer(s) Assigned
19 Jan 2021Review(s) Completed, Editorial Evaluation Pending
19 Jan 2021Editorial Decision: Revise Minor
28 Jan 20211st Revision Received
28 Jan 2021Reviewer(s) Assigned
02 Feb 2021Review(s) Completed, Editorial Evaluation Pending
02 Feb 2021Editorial Decision: Accept