Higher humoral response in ileal versus colonic Crohn's disease

Abstract

Despite its interest for the development of personalized medicine, the immunological differences between ileal and colonic Crohn’s disease (CD) have been understudied. For unknown reasons, some circulating antibodies are associated with CD location (ileal CD: anti-Saccharomyces cerevisiae antibodies, anti-flagellins antibodies, anti-granulocyte macrophage-colony stimulating factor autoantibodies, and some pancreatic autoantibodies; colonic CD: perinuclear antineutrophil cytoplasmic autoantibodies). Based on these observations, we hypothesized that, in tissues, the humoral response differs between ileal and colonic CD. This hypothesis was tested by analysing the expression of IgA1, IgA2, IgG1, IgG2, IgG3, IgM, and immunoglobulin J chain (IGJ) in our previous dataset comparing the proteome of ulcer edges and adjacent normal mucosa (paired design) in the ileum (4 428 proteins screened in 16 biopsies) and colon (5 204 proteins screened in 16 biopsies) of 16 patients with CD. All these proteins were increased in ileal ulcer edges compared with adjacent normal mucosa, whereas only IgG3 was increased in colonic ulcer edges compared with adjacent normal mucosa. These data highlight the distinct role of humoral immunity in ileal and colonic CD, thereby opening a new avenue of research for developing therapies tailored to CD location.