The changing immunological paradigm in coeliac disease

Decreased numbers of circulating plasmablasts and differences in IgA1-plasmablast homing to skin in coeliac disease and dermatitis herpetiformis

“…Two major findings were detected: a significant decrease in the numbers of circulating plasmablasts in CD and partly in DH, and an increased skinhoming potential of IgA1-plasmablasts compared with IgA2 cells in DH, but not in CD. Several studies have shown increased numbers of IgA-and IgG-containing cells in the intestinal mucosa of adult patients with CD [13][14][15][16][17] and IgA1 deposits in the skin of patients with DH [4,5,18]. For the first time, to our knowledge, the present study investigated the population of circulating plasmablasts, ISC, in adults with gluten enteropathy.…”

“…The decrease in circulating ISC in adults could imply an impairment of the local intestinal defence mechanisms leading to reduced induction of gut-directed ISC into the circulation. However, several earlier studies have shown increased numbers of IgA-, IgG-and IgM-plasma cells in the small bowel mucosa of untreated CD [15][16][17] and DH patients [17,43,44], accompanied by an increased production of these Igs from cultured mucosal biopsies [15]. After treatment, the mucosal plasma cell numbers have proved to decrease but not reach the levels of healthy individuals [15,16].…”

“…The lower proportion of L-selectin + cells among patient ISC compared with control ISC thus appears to reflect the dominance of mucosa-originating cells among ISC with a decreased ability to home to systemic sites. Conversely, it could reflect an increased homing of these cells to inflammatory sites in the intestine, in accordance with increased numbers of plasma cells in the intestinal lamina propria [15][16][17].…”

“…These autoantibodies may contribute to the destruction of the integrity of villus structure, and therefore B cell responses also appear pertinent to the pathogenesis of the disease [12]. Several studies have shown increased numbers of IgA-and IgG-containing cells in the intestinal mucosa of adult patients with CD [13][14][15][16][17] and IgA-deposits in the skin of patients with DH [4,5,18]. The present study is the first, to our knowledge, to investigate the influence of gluten enteropathy on the population of circulating plasmablasts, a cell population representing the most differentiated cell type of B cell lineage in the circulation, before homing into tissues.…”

Ascorbate-dependent decrease of the mucosal immune inflammatory response to gliadin in coeliac disease patients

“…1,2 The most accepted model of the CD immunopathogenesis is the two-signal model, which establishes that gliadin has a dual effect on the CD duodenum, triggering the development of an innate immune response in the epithelium, and activating an adaptive immune response controlled by gluten-reactive T cells with a Th1 cytokine profile. 3,4 Innate immunity, and specifically interleukin (IL)-15, 5,6 plays a key role in the development of CD through a DQ2-independent mechanism. 7 The induction of IL-15 seems to be involved in the initial stages of the disease leading to epithelial stress, increase tightjunction permeability, enterocyte apoptosis and dendritic cell (DC) activation, 5,6,8---12 facilitating the development of the secondary adaptive response.…”