Crohn’s disease and ulcerative colitis – current view on genetic determination, immunopathogenesis and biologic therapy

Česká verzia

Authors: M. Buc
Authors place of work: Imunologický ústav, Lekárska fakulta UK, Bratislava, Slovenská republika
Published in the journal: Epidemiol. Mikrobiol. Imunol. 66, 2017, č. 4, s. 189-197
Category: Souhrnné sdělení

Summary

Crohn’s disease (CD) and ulcerative colitis (UC) are chronic inflammatory disorders of the intestine, also called inflammatory bowel diseases (IBD), which are not caused by pathogenic microorganisms but result from non-specific inflammatory processes in the bowel. IBD are polygenic diseases, as evidenced by the genome-wide association studies (GWAS), which have discovered more than 200 genes or genetic regions to be associated with IBD. Some of them are specific for CD or UC; however, there are 110 overlapping genes. In the pathogenesis of CD, activation of adaptive immunity mediated by T_H1, T_H17, or T_H1/T_H17 cells is induced because of disturbances in the mechanisms of innate immunity and autophagocytosis. By comparison, the major events that trigger autoimmune processes in UC are an increased translocation of commensal bacteria into the submucosa because of loose inter-epithelial connections with subsequent activation of ILC2, T_H9, T_H2, and NKT cells. Knowledge of the pathogenesis of a disease enables an effective therapy, which is especially true for biological therapy. It is noteworthy that monoclonal antibodies directed against the major protagonists underlying both CD and UC have failed. It points to the complexity of immunopathologic processes that run in both diseases. One can suppose that a blockade of one inflammatory pathway is circumvented by an alternative pathway. TNF is the principal pro-inflammatory cytokine that plays a major role in CD and UC as well. It was therefore decided to treat IBD patients with anti-TNF monoclonal antibodies, infliximab or adalimumab. Approximately one half of the CD patients and one third of the UC patients respond to this treatment.

Keywords:
Crohn – ulcerative colitis – autophagocytosis – autoantibodies – T cells subsets – innate lymphoid cells – anti-TNF treatment

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