RORγt inhibition selectively targets IL-17 producing iNKT and γδ-T cells enriched in Spondyloarthritis patients

Dysregulated IL-23/IL-17 responses have been linked to psoriatic arthritis and other forms of spondyloarthritides (SpA). ROR gamma t, the key Thelperl7 (Th17) cell transcriptional regulator, is also expressed by subsets of innate-like T cells, including invariant natural killer T (iNKT) and gamma delta-T cells, but their contribution to SpA is still unclear. Here we describe the presence of particular ROR gamma t(+)T-be(lo)PLZF(-) iNKT and gamma delta-hi T cell subsets in healthy peripheral blood. ROR gamma t(+) iNKT and gamma delta-hi T cells show IL-23 mediated Th17-like immune responses and were clearly enriched within inflamed joints of SpA patients where they act as major IL-17 secretors. SpA derived iNKT and gamma delta-T cells showed unique and Th17-skewed phenotype and gene expression profiles. Strikingly, ROR gamma t inhibition blocked gamma delta 17 and iNKT17 cell function while selectively sparing IL-22(+) subsets. Overall, our findings highlight a unique diversity of human ROR gamma t(+) T cells and underscore the potential of ROR gamma t antagonism to modulate aberrant type 17 responses

Etiological factors and underlying conditions in patients with leucocytoclastic vasculitis

This study concerns a retrospective analysis of 63 consecutive patients presenting with leucocytoclastic vasculitis at the Departments of Dermatology or Rheumatology of the University Hospital Ghent (Belgium) (period 1988 - 1993). The diagnosis of leucocytoclastic vasculitis was confirmed by histopathology in all cases. All patients were screened for underlying causes, including drugs, infection, systemic autoimmune disease or neoplasia. In 34 patients, an etiological factor was identified: drugs (5 patients), infection (6 patients), drugs or infection (4 patients), systemic autoimmune disease (10 patients), Henoch Shonlein (6 patients), neoplasia (2 patients) and cryoglobulinemia (1 patient). In the group of patients with leucocytoclastic vasculitis in the context of systemic autoimmune disease, 4 patients suffered from systemic lupus erythematosus, 2 from Wegener's disease, 2 from Behcet's disease, 1 from polyarteritis nodosa and 1 from rheumatoid arthritis. In the remaining 29 patients, no cause for the vasculitis could be identified

Improvements in productivity and increased participation in daily activities over 52 weeks of certolizumab pegol treatment of rheumatoid arthritis: results of a Belgian observational study

Objectives: To report changes in productivity and social participation - alongside clinical and patient-reported outcomes (PROs) - in patients with rheumatoid arthritis (RA) receiving certolizumab pegol (CZP) during routine clinical practice in Belgium. Methods: This was a prospective, non-interventional study, in which patients were prescribed CZP at their physicians' discretion and followed during routine clinical visits. The primary outcomes were household productivity and social participation at the last visit (~52 weeks), measured through responses to the Work Productivity Survey. Secondary outcomes included workplace productivity and achievement of DAS28(ESR) clinical response, low disease activity and remission at the last visit. Baseline demographics and adverse events (AEs) were recorded for all patients who received ≥1 dose CZP. Results: A total of 141 patients were enrolled in the study, of whom 119 (84.4%) formed the full analysis set (received ≥1 dose CZP and had ≥1 post-baseline measurement for ≥1 primary outcome). At Visit 1 (baseline), patients reported an average of 11.0 paid work days, 16.8 household work days and 5.5 days of social participation affected by their disease over the previous month. Rapid improvements in household productivity and social participation were evident from Visit 2 (2-8 weeks). By the final visit, mean improvements were observed for all aspects of productivity, participation and clinical/PROs. A total of 24 AEs were reported. Conclusion: CZP has a positive impact on productivity and social participation in patients with RA in the Belgian daily practice setting, with safety and efficacy profiles that mirror those observed in the trial setting.status: publishe

Gut inflammation in psoriatic arthritis: a prospective ileocolonoscopic study

Objective. Some forms of psoriatic arthritis (PsA) are classified as spondylarthropathy, and subclinical gut inflammation is found in spondylarthropathies. Our study was designed to determine if inflammatory gut lesions were also present in PsA, and if the prevalence of subclinical gut involvement was different in the subgroups of this disease. The relationship with HLA subtypes was also determined. Methods. Ileocolonoscopy was performed on 64 patients with PsA (37 men, 27 women). Results. Inflammatory gut lesions were found in 10 of the 64 patients (16%): in 3 of the 15 patients (20%) with oligoarthritis and in 7 of the 23 patients (30%) with axial involvement. None of the 26 patients with polyarthritis showed these lesions. The prevalence of HLA-B27, Bw62, and B17 was significantly raised in our total group of patients with PsA. HLA-B27 and Bw62 were significantly more prevalent in patients with gut inflammation, 60 and 50%, respectively. Conclusion. Gut inflammation is only present in PsA subgroups that belong to the spondylarthropathy concept. This suggests that the gut plays a role in the pathogenesis of locomotor inflammation in these subgroups. The prevalence of gut inflammation in psoriatic spondylarthropathy is significantly lower than in nonpsoriatic spondylarthropathies. Consequently, not only the gut but also the skin may be a portal of entry for causative antigens in PsA

The evolution of spondyloarthropathies in relation to gut histology, 3: relation between gut and joint

Objective. To study prospectively the clinical evolution of different forms of spondyloarthropathy (SpA) in relation to the evolution of gut histology in consecutive ileocolonoscopic biopsy specimens. Methods. Ileocolonoscopy was performed in 49 patients with SpA (34 men, 15 women). They also underwent clinical, laboratory, and radiological examinations. Two to 9 years later, a 2nd and sometimes a 3rd or 4th ileocolonoscopy was performed, and the other examinations were repeated. Results. At first ileocolonoscopy, 34 patients (69%) showed inflammatory gut lesions. At the 2nd ileocolonoscopy, 16 patients (32%) were in clinical remission; none were found to have inflammatory gut lesions. Of the 33 patients with persistent locomotor inflammation, 14 had persistent inflammatory gut lesions, predominantly the chronic type. Of these 14 patients, 6 had developed inflammatory bowel disease (IBD). None of the 15 patients with an initially normal gut histology had gut inflammation at 2nd examination. Of the 9 with initially acute lesions, 3 developed chronic lesions (1 Crohn's disease). Initial chronic lesions in 25 patients persisted in 9, of whom 5 had developed IBD. Seven of the 19 patients with non-SpA ankylosing spondylitis (non-AS-SpA) developed ankylosing spondylitis (AS); all had initially presented inflammatory gut lesions, which persisted at 2nd examination. In the 11 patients with more than 2 consecutive ileocolonoscopies, clinical remission was always associated with normal gut histology, and flares of the joint disease were related temporally to the reappearance of gut inflammation. Conclusion. This study demonstrates the close relationship between gut and locomotor inflammation in SpA. Clinical remission was always associated with normal gut histology, whereas active locomotor inflammation was usually associated with the presence of gut inflammation. Absence of gut inflammation in the SpA is a good prognostic indicator, since gut inflammation or IBD never develops in these patients. Evolution of non-AS-SpA to full blown AS or of uncomplicated SpA to a farm of IBD was always associated with gut inflammation at disease onset