Objective. Obesity is a mild, long-lasting inflammatory disease and, as such, could increase the inflammatory burden of rheumatoid arthritis (RA). The study aim was to determine whether obesity represents a risk factor for a poor remission rate in RA patients requiring anti-tumor necrosis factor ␣ (anti-TNF␣) therapy for progressive and active disease despite treatment with methotrexate or other disease-modifying antirheumatic drugs.

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Objectives IL-23 has been implicated in the pathogenesis of Ankylosing Spondylitis (AS). Aim of the study was to clarify the mechanisms underlying the increased IL-23 expression in the gut of AS patients. Methods Consecutive gut biopsies from 30 HLA-B27+ AS patients, 15 Crohn’s disease (CD) patients and 10 normal subjects were obtained. Evidence for HLA-B27 misfolding was studied. Unfolded protein response (UPR) and autophagy were assessed by rt-PCR and immunohistochemistry. The contribution of UPR and autophagy in the regulation of IL-23 expression was evaluated in in vitro experiments on isolated lamina propria mononuclear cells (LPMCs). Results Intracellular co-localization of SYVN1 and FHCs but not a significant over-expression of UPR genes was observed in the gut of AS patients. Conversely, up-regulation of the genes involved in the autophagy pathway was observed in the gut of AS and CD patients. Immunohistochemistry showed an increased expression of LC3II, ATG5 and ATG12 but not of SQSTM1 in the ileum of AS and CD patients. LC3II was expressed among infiltrating mononuclear cells and epithelial cells resembling Paneth cells and co-localized with ATG5 in AS and CD. Autophagy but not UPR was required to modulate the expression of IL-23 in isolated LPMCs of AS patients with chronic gut inflammation, CD patients and controls. Conclusions Our data suggest that HLA-B27 misfolding occurs in the gut of AS patients and is accompanied by activation of autophagy rather than an unfolded protein response. Autophagy appears to be associated with intestinal modulation of IL-23 in AS.

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Objective. The intestinal inflammation observed in patients with ankylosing spondylitis (AS) is characterized by an overexpression of interleukin-23 (IL-23). IL-23 is Conclusion. Our findings indicate that overexpression of IL-22, together with an increased number of IL-22-producing NKp44؉ NK cells, occurs in the gut of AS patients, where it appears to play a tissue-protective role.The asymptomatic ileal inflammation observed in patients with ankylosing spondylitis (AS) is immunologically characterized by the overexpression of interleukin-23 (IL-23). This overexpression, however, does not appear to be sufficient to induce Th17 polarization (1). Protective immunologic mechanisms, such as the expansion of IL-10-producing Treg cells, could, at least in part, explain the absence of a clear Th17 response despite the high levels of IL-23 observed in AS patients (2).Although the primary focus of investigations of IL-23 function has been its effect on the adaptive immune system through the regulation of the Th17 pathway, recent studies of the gut suggest an important role for IL-23 in regulating innate immune responses (3-8). These studies have in fact identified a subset of IL-23-responsive human lamina propria natural killer (NK) cells that contribute to intestinal mucosa immunity. Lamina propria NK cells comprise 2 main populations, interferon-␥ (IFN␥)-producing NKp46ϩ NK cells and IL-22-producing NKp44ϩ NK cells, which are balanced in normal human intestinal mucosa (9). This balance is disrupted in the inflamed mucosa of patients Supported by a grant from the