Mucosal-associated invariant T cells in patients with axial spondyloarthritis.

Background: Several studies implicate Th17-cells and its cytokine (IL-17) in disease pathogenesis of spondyloarthritis (SpA), with available evidence supporting a pathogenic role of CD8+ T-cells. However, data on the involvement of CD8+ mucosal-associated invariant T-cells (MAIT) and their phenotypic characterization and inflammatory function including IL-17 and Granzyme A production in a homogenous population of SpA-patients with primarily axial disease (axSpA) are lacking. Objectives: Quantify and characterize the phenotype and function of circulating CD8+MAIT-cells in axSpA-patients with primarily axial disease. Methods: Blood samples were obtained from 41 axSpA-patients and 30 age- and sex-matched healthy controls (HC). Numbers and percentages of MAIT-cells (defined as CD3+CD8+CD161highTCRVα7.2 +) were determined, and production of IL-17 and Granzyme A (GrzA) by MAIT-cells were examined by flow cytometry upon in vitro stimulation. Serum IgG specific for CMV was measured by ELISA. Results: No significant differences in numbers and percentages of circulating MAIT-cells were found between axSpA-patients and HCr zijn meer resultaten de centrale memory CD8 T cellen. cellen van patirculating MAIT cells.. Further phenotypic analysis revealed a significant decrease in numbers of central memory MAIT-cells of axSpA-patients compared to HC. The decrease in central memory MAIT-cells in axSpA patients was not attributed to an alteration in CD8 T-cell numbers, but correlated inversely with serum CMV-IgG titers. Production of IL-17 by MAIT-cells was comparable between axSpA-patients and HC, whereas a significant decrease in the production of GrzA by MAIT-cells from axSpA-patients was observed. Conclusions: The decrease in cytotoxic capability of circulating MAIT-cells in axSpA-patients might implicate that these cell types migrate to the inflamed tissue and therefore associate with the axial disease pathogenesis.

Extraskeletal Manifestations in Axial Spondyloarthritis Are Associated With Worse Clinical Outcomes Despite the Use of Tumor Necrosis Factor Inhibitor Therapy.

OBJECTIVE: To investigate the prevalence and 4-year incidence of acute anterior uveitis (AAU), inflammatory bowel disease (IBD) and psoriasis (PsO), and to explore associations of newly developed extraskeletal manifestations (ESMs) with clinical disease outcome in a large cohort of patients with axial spondyloarthritis (axSpA). METHODS: All consecutive patients included in the Groningen Leeuwarden Axial Spondyloarthritis (GLAS) cohort between 2004 and 2011 were analyzed. History of ESMs at baseline and newly developed ESMs during 4-year follow-up were only recorded when diagnosis by an ophthalmologist, gastroenterologist, or dermatologist was present. RESULTS: Of the 414 included patients with axSpA, 31.4% had a positive history of ≥ 1 ESMs: 24.9% AAU, 9.4% IBD, and 4.3% PsO. History of PsO was significantly associated with more radiographic damage, especially of the cervical spine. Of the 362 patients with 4-year follow-up data, 15.7% patients developed an ESM: 13.3% patients had AAU (of which 3.6% had a first episode and 9.7% had recurrent AAU), 1.9% developed IBD, and 0.8% developed PsO. Patients with newly developed ESMs (without history of ESMs) had worse Ankylosing Spondylitis Quality of Life scores (mean 10.0 vs. 5.8, P = 0.001), larger occiput-wall distance (median 6.3 vs. 2.0, P = 0.02) and more limited modified Schober test (mean 12.6 vs. 13.6, P = 0.01) after 4 years of follow-up. The majority of patients developing an ESM used anti-tumor necrosis factor therapy. CONCLUSION: History of ESMs was present at baseline in one-third of patients with axSpA. The 4-year incidence of ESMs was relatively low, but patients who developed a new ESM reported worse quality of life.