A 61-year-old man presented with weight loss, bilateral ocular redness, blurred vision, and sensorineural hearing loss. Fluorodeoxyglucose-position emission tomography/computed tomography demonstrated an uptake in the ascending and descending aorta, abdominal aorta and femoral arteries. Atypical Cogan's syndrome complicated with large-vessel vasculitis (LVV) was diagnosed. He was treated with high-dose prednisolone and subcutaneous tocilizumab (162 mg/week), resulting in successful improvements in his ocular and vascular involvements. Although there is currently no established treatment strategy for LVV associated with Cogan's syndrome, our case and literature review suggest that tocilizumab is a viable treatment option for this rare but life-threatening complication.
Objectives
T cells adhere to enthesis fibrocartilage via integrins and intrinsically require IL-17RA-mediated signals to maintain their effector function. We analyzed CD29+IL-17RA+T cells in inflamed lesions and peripheral blood in patients with spondyloarthritis (SpA) and investigated their association with disease activity and therapeutic response.
Methods
Transcriptome analysis of synovial fluid T cells from psoriatic arthritis was performed by publicly available bulk-cell RNA-sequencing data. Blood samples were obtained from healthy controls (n = 37), rheumatoid arthritis (RA, n = 12), IgG4-related disease (IgG4-RD, n = 12), large vessel vasculitis (LVV, n = 12), and SpA (n = 28) and were analyzed by flow cytometry.
Results
T cells in the inflamed joints of psoriatic arthritis showed CD29 and IL-17RA expression. CD29+IL-17RA+ T cells showed enriched CXCR3+CD45RA+ effector cells and activation of the spleen tyrosine kinase (Syk), nuclear factor κB (NF-κB), and Janus kinase/signal transducer and activator of transcription (JAK-STAT) pathways. The proportion of peripheral blood CD29+IL-17RA+ T cells was significantly increased in patients with SpA than in patients with RA, IgG4-RD, or LVV and in healthy controls. Based on the ASDAS-CRP scores, the proportion of CD29+IL-17RA+ T cells was positively correlated with disease activity in treatment-naïve patients with active SpA. Anti-IL-17 but not anti-TNF monoclonal antibodies reduced CD29+IL-17RA+ T cells.
Conclusions
CD29+IL-17RA+ T effector cells with enhanced Syk, NF-κB, and JAK-STAT pathways was specifically increased in SpA and was correlated with disease activity, implicating a role of this newly identified T cell population in the pathogenesis. Anti-IL-17 monoclonal antibodies may be effective for patients by reducing this pathogenic T cell population.
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