Analysis of IL-17+ cells in facet joints of patients with spondyloarthritis suggests that the innate immune pathway might be of greater relevance than the Th17-mediated adaptive immune response

Abstract

IntroductionIn this study, we analysed the number of IL-17+ cells in facet joints, in the peripheral blood (PB) and synovial fluid (SF) of spondyloarthritis (SpA) patients and compared these results with those of patients with other rheumatic diseases and controls.MethodsImmunohistochemical analysis of IL-17+ cells was performed in facet joints of 33 ankylosing spondylitis (AS) patients and compared with data from 20 osteoarthritis (OA) patients. The frequency of IL-17+CD4+ T cells in PB and SF of SpA patients (PB n = 30, SF n = 11), rheumatoid arthritis (RA) patients (PB n = 14, SF n = 7), OA patients (PB n = 10) and healthy controls (PB n = 12) was analysed after stimulation with Staphylococcus aureus Enterotoxin B and phorbol 12-myristate 13-acetate/ionomycin and quantified by flow cytometry.ResultsIn AS facet joints, the frequency of IL-17-secreting cells was significantly higher than in samples obtained from OA patients (P < 0.001), with a slight predominance of IL-17+ cells among the mononuclear cells (61.5% ± 14.9%) compared to cells with polysegmental nuclei. Immunofluorescence microscopy revealed that the majority of IL-17+ cells were myeloperoxidase-positive (35.84 ± 13.06/high-power field (HPF) and CD15+ neutrophils (24.25 ± 10.36/HPF), while CD3+ T cells (0.51 ± 0.49/HPF) and AA-1+ mast cells (2.28 ± 1.96/HPF) were less often IL-17-positive. The frequency of IL-17+CD4+ T cells in the PB and SF of SpA patients did not differ significantly compared to RA patients, OA patients or healthy controls.ConclusionsOur data suggest an important role for IL-17 in the inflammatory processes in AS. However, the innate immune pathway might be of greater relevance than the Th17-mediated adaptive immune response.

In Situ Analysis of Interleukin–23– and Interleukin‐12–Positive Cells in the Spine of Patients With Ankylosing Spondylitis

“…In an earlier study (26) we showed that IL-17 is highly expressed in subchondral bone marrow cells, but the source was MPOpositive and CD15ϩ myeloid precursors and neutrophils and tryptase-positive mast cells, rather than CD3ϩ (CD4ϪCD8Ϫ) cells. Nonetheless, the mouse data indicate that the effector cells stimulated by IL-23 belong to the innate as opposed to the adaptive immune system in AS.…”

Sexual Dimorphism in the Th17 Signature of Ankylosing Spondylitis

“…Recent work has implicated the Th17 axis in AS, through immunophenotyping of blood cells (7), identifying IL-23-and IL-17A-positive cells in affected joints (8), and identifying the association of Th17 cell-related genes in genome-wide association studies (GWAS) (9). These conclusions are anchored in studies that are largely dominated by male patients, with a significant underrepresentation of female patients.…”

Infectious Spondylitis-Associated &lt;i&gt;Staphylococcus aureus&lt;/i&gt; with Virulence Gene &lt;i&gt;pvl&lt;/i&gt; or &lt;i&gt;tst&lt;/i&gt; Causes More Necrosis than Apoptosis in Human Alveolar Basal Epithelial Cell Line A549

“…Furthermore, cytokines are also possible markers for diagnosis. For example, IL-17 plays an important role in the inflammatory process in ankylosing spondylitis [31]. To predict the clinical outcome of patients with bacterial pyogenic vertebral osteomyelitis, an erythrocyte sedimentation rate (ESR) over 55 mm/h and a C-reactive protein (CRP) value of 2.75 mg/dL at the fourth week are useful markers [6].…”