Inflammatory bowel disease: is it a primary immunodeficiency?

Abstract

Inflammatory bowel diseases (IBD) such as ulcerative colitis and Crohn's disease are chronic and relapsing conditions, characterized by abdominal pain, diarrhea, bleeding and malabsorption. IBD has been considered a hyperinflammatory state due to disturbed interactions between the immune system and the commensal bacterial flora of the gut. However, there is evidence that Crohn's disease might be the consequence of a reduced release of pro-inflammatory cytokines and an impaired acute inflammatory response, thereby suggesting that IBD might be an immunodeficiency rather than an excessive inflammatory reaction. This theory has been supported by observations in patients with primary immunodeficiencies such as the Wiskott-Aldrich syndrome and IPEX (immunodysregulation, polyendocrinopathy, enteropathy, X-linked syndrome). In contrary, defects in the anti-inflammatory down-regulation of the immune response as they are seen in patients with Mendelian defects in the IL10 signaling pathway support the hyper-inflammatory theory. In this review, we describe and discuss primary immunodeficiencies associated with IBD and show that the bowel is a highly sensitive indicator of dysregulations, making IBD a model disease to study and identify key regulators required to balance the human mucosal immune system.

miR-20b, miR-98, miR-125b-1*, and let-7e* as new potential diagnostic biomarkers in ulcerative colitis

“…Moreover, it has been found that miRNAs are differentially expressed in ulcerative colitis (UC) and Crohn's disease (CD) [27] , the two main forms of IBD. However, the pathogenesis of IBD still remains enigmatic [28] , but the identification of differentially expressed miRNAs and subsequent understanding of their molecular mechanisms appear to provide new ways to reveal the pathophysiology, discover new diagnostic biomarkers, and develop new therapeutics [27] .…”

Autoimmunity in Primary Antibody Deficiencies

“…The most common autoimmune disorders in PADs are immune thrombocytopenic purpura (ITP) and autoimmune hemolytic anemia (AIHA) [7]. Moreover, other diseases including autoimmune thyroid disease [8], type 1 diabetes (T1D) [9], rheumatoid arthritis (RA) [10], systemic lupus erythematosus (SLE) [11], dermatomyositis [12], inflammatory bowel diseases (IBD) [13], alopecia areata [11], vitiligo [8], and glomerulonephritis [14] are also common in PADs due to the lack of self-tolerance [15]. …”

Pharmacological Characterization of a Potent Inhibitor of Autotaxin in Animal Models of Inflammatory Bowel Disease and Multiple Sclerosis

“…Pain is usually caused by abdominal cramps, owing to irritation of the nerves by inflammatory cytokines and mediators sensitizing the primary afferents and muscles controlling intestinal contractions (Bielefeldt et al, 2009;Docherty et al, 2011;Glocker and Grimbacher, 2012). Pain may be the only symptom of disease activity in some patients, and about one-sixth of IBD patients are chronically treated with opioids (Edwards et al, 2001;Cross et al, 2005;Lix et al, 2008;Bielefeldt et al, 2009).…”