Azathioprine therapy selectively ablates human Vδ2+ T cells in Crohn’s disease

Abstract Background and Aims Tumour necrosis factor [TNF]α- and IL-17A-producing T cells are implicated in Crohn’s disease [CD]. Tissue-resident memory T [TRM] cells are tissue-restricted T cells that are regulated by PR zinc finger domain 1 [PRDM1], which has been implicated in pathogenic Th17 cell responses. TRM cells provide host defence but their role in CD is unknown. We thus examined CD4+ TRM cells in CD. Methods Colon samples were prospectively collected at endoscopy or surgery in CD and control subjects. Flow cytometry and ex vivo assays were performed to characterise CD4+ TRM cells. Results CD4+ TRM cells are the most abundant memory T cell population and are the major T cell source of mucosal TNFα in CD. CD4+ TRM cells are expanded in CD and more avidly produce IL-17A and TNFα relative to control cells. There was a unique population of TNFα+IL-17A+ CD4+ TRM cells in CD which are largely absent in controls. PRDM1 was highly expressed by CD4+ TRM cells but not by other effector T cells. Suppression of PRDM1 was associated with impaired induction of IL17A and TNFA by CD4+ TRM cells Conclusions CD4+ TRM cells are expanded in CD and are a major source of TNFα, suggesting that they are important in CD. PRDM1 is expressed by TRM cells and may regulate their function. Collectively, this argues for prospective studies tracking CD4+ TRM cells over the disease course.

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The effect of early immunosuppressive therapy on the rate of resections performed in patients with Chron’s disease, in Veszprém county, Hungary, a population-based cohort study

Orvosi Hetilap ◽

10.1556/oh.2012.29331 ◽

2012 ◽

Vol 153 (14) ◽

pp. 541-552 ◽

Cited By ~ 2

Author(s):

Petra Anna Golovics ◽

Péter László Lakatos ◽

Gyula Dávid ◽

Tünde Pandur ◽

Zsuzsanna Erdélyi ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Medical Therapy ◽

Propensity Scores ◽

Age At Onset ◽

Population Based ◽

Systemic Steroid ◽

Azathioprine Therapy ◽

The Past ◽

Cox Analysis

Medical therapy for Crohn’s disease has changed significantly over the past 20 years with the increasing use of immunosuppressants. In contrast, surgery rates are still high and evidence about the the changes in the outcome of Crohn’s disease over the past decades is scarce. Aims: The objective of this study was to analyze the evolution of the surgical rates and medical therapy in the population-based Veszprém county database. Methods: Data of 506 Crohn’s disease patients were analyzed (age at diagnosis: 31.5 years, SD: 13.8 years). Both hospital and outpatient records were collected and comprehensively reviewed. The study population was divided into three groups based on the year of diagnosis (cohort A: 1977–1989, cohort B: 1990–1998 and cohort C: 1999–2008). Results: Overall azathioprine, systemic steroid, and biological (only available after 1998) exposure was 45.8, 68.6, and 9.5%, respectively. The 1 and 5-year probabilities of azathioprine use were 3.2 and 6.2% in cohort A, 11.4 and 29.9% in cohort B, and 34.8 and 46.2% in cohort C. In multivariate analysis, decade of diagnosis (P<0.001), age at onset (P = 0.008), disease behavior at diagnosis (P<0.001), and need for systemic steroids (P<0.001) were significantly associated with the time to initiation of azathioprine therapy. Early azathioprine use was significantly associated with the time to intestinal surgery in Crohn’s disease patients; in a multivariate Cox analysis (HR: 0.43, 95% confidence interval (CI): 0.28–0.65) and after matching on propensity scores for azathioprine use (HR: 0.42,95% CI:0.26–0.67). Conclusions: This population-based inception cohort showed that reduction in surgical rates was independently associated with increased and earlier azathioprine use. Orv. Hetil., 2012, 153, 541–552.

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