Identification of a Disease-Associated Network of Intestinal Immune Cells in Treatment-Naive Inflammatory Bowel Disease.

Chronic intestinal inflammation underlies inflammatory bowel disease (IBD). Previous studies indicated alterations in the cellular immune system; however, it has been challenging to interrogate the role of all immune cell subsets simultaneously. Therefore, we aimed to identify immune cell types associated with inflammation in IBD using high-dimensional mass cytometry. We analyzed 188 intestinal biopsies and paired blood samples of newly-diagnosed, treatment-naive patients (n=42) and controls (n=26) in two independent cohorts. We applied mass cytometry (36-antibody panel) to resolve single cells and analyzed the data with unbiased Hierarchical-SNE. In addition, imaging-mass cytometry (IMC) was performed to reveal the spatial distribution of the immune subsets in the tissue. We identified 44 distinct immune subsets. Correlation network analysis identified a network of inflammation-associated subsets, including HLA-DR+CD38+ EM CD4+ T cells, T regulatory-like cells, PD1+ EM CD8+ T cells, neutrophils, CD27+ TCRγδ cells and NK cells. All disease-associated subsets were validated in a second cohort. This network was abundant in a subset of patients, independent of IBD subtype, severity or intestinal location. Putative disease-associated CD4+ T cells were detectable in blood. Finally, imaging-mass cytometry revealed the spatial colocalization of neutrophils, memory CD4+ T cells and myeloid cells in the inflamed intestine. Our study indicates that a cellular network of both innate and adaptive immune cells colocalizes in inflamed biopsies from a subset of patients. These results contribute to dissecting disease heterogeneity and may guide the development of targeted therapeutics in IBD.

Dysfunctional cognitions, anxiety and depression in irritable bowel syndrome.

GOALS AND BACKGROUND: Patients with irritable bowel syndrome (IBS) have significantly impaired quality of life (QoL). We investigated the presence of dysfunctional cognitions, anxiety, and depression symptoms and their impact on daily symptoms and QoL in a large IBS cohort. STUDY: A total of 268 IBS patients (Rome II criteria, age 18 to 65 y) were included. Patients completed a 2-week daily symptom diary. The Short Form-36 was used to score QoL. The 31-items Cognitive Scale for Functional Bowel Disorders (CSFBD) and the Hospital Anxiety and Depression Scale (HADS) were used to analyze the psychological factors. RESULTS: Possible anxiety and depression disorders were present in 30% and 22% of IBS patients, respectively. Patients with anxiety and depression had significantly higher mean symptom scores, impaired QoL, and higher CSFBD scores (P<0.01). Physical and mental QoL were both affected by depression (HADS-D) and dysfunctional cognitions (P<0.01). Only physical QoL, not mental QoL, was affected by referral type (hospital setting vs. community based; P<0.01). Only mental QoL was affected by anxiety (HADS-A) (P<0.01). Dysfunctional cognitions independently of anxiety and depression influenced QoL and IBS symptoms. CONCLUSIONS: In this IBS cohort, dysfunctional cognitions independently influence physical and mental QoL and symptom severity. Presence of possible anxiety and depression disorders resulted in higher symptoms, lower QoL, and higher CSFBD scores. The results point toward an important role of psychological factors, especially dysfunctional cognitions on QoL and symptom scores in IBS patients.