Mucosal antibodies in inflammatory bowel disease are directed against intestinal bacteria.

Macpherson, Andrew J.; Khoo, U Y; Forgács, I; Philpott‐Howard, John; Bjarnason, Ingvar

doi:10.1136/gut.38.3.365

Cited by 395 publications

(231 citation statements)

References 40 publications

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“…This regulatory role for SIgA has been previously inferred from correlations of IgA deficiency in humans with various autoimmune diseases and inflammatory conditions, such as celiac disease (14,15) and IBD (43). It has been suggested that IgA deficiency might result in undue triggering of the immune response to gluten in the case of celiac disease (19) and to the intestinal flora in the case of IBD (18,44), Ags to which the immune system is usually tolerant. While oral CD8 ϩ T cell tolerance to OVA was induced in pIgR Ϫ/Ϫ mice in this study, the propensity of these mice to abrogate a previously established tolerance was not investigated.…”

Section: Discussionmentioning

confidence: 99%

“…Other studies have shown that the enteric bacterial environment has a major impact on the severity of inflammatory bowel disease (IBD), such that experimental IBD is abrogated in germ-free animals (20,21). Furthermore, the high levels of mucosal IgG Abs in UC are largely directed against intestinal bacteria (18). This suggests that intolerance to intestinal flora may trigger UC, and also that a deficiency in IgA, which is a predisposing factor in UC, might be one of the causes of this intolerance.…”

mentioning

confidence: 99%

“…Such a regulatory function may explain the correlation between selective IgA deficiency and conditions such as celiac disease (CD) (14 -16) and ulcerative colitis (UC) (17,18) in humans. Although it has been well established that CD is triggered by peptides from the wheat protein gliadin (19), the factors that predispose individuals to CD and their role in disease induction are less clearly understood.…”

mentioning

confidence: 99%

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Role of the Polymeric Ig Receptor in Mucosal B Cell Homeostasis

Uren

Johansen

Wijburg

et al. 2003

The Journal of Immunology

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Secretory IgA (SIgA) is the most characteristic component of the mucosal immune system and has long been considered the major protective factor that prevents pathogens from invading hosts through the mucosae. Recent studies, however, have suggested that complete immunity against a range of mucosal bacterial and viral pathogens can be achieved in the absence of IgA. Therefore, to further dissect the role of SIgA, we generated mice deficient in the polymeric Ig receptor (pIgR−/− mice). As a result of an inability to transport dimeric IgA to the secretions, pIgR−/− mice are deficient in SIgA and accumulate circulating dimeric IgA, with serum levels 100-fold greater than those observed in normal mice. Examination of lamina propria mononuclear cells showed that pIgR−/− mice had ∼3 times as many IgA-secreting cells as C57BL/6 mice. Further analysis showed that these cells displayed the differentiated IgA+ B220− phenotype and accounted for a 2-fold increase in the number of lamina propria blast cells in the pIgR−/− mice. Subsequent experiments showed that OVA-specific CD4+ T cell expansion following OVA feeding was not elevated in pIgR−/− mice. Furthermore, no differences in CD8+ T cell tolerance or induction of influenza virus-specific CD8+ T cells were detected in pIgR−/− mice compared with controls. Therefore, while SIgA is clearly involved in maintaining some parameters of mucosal homeostasis in the intestine, the mechanisms associated with its barrier function and the clinical consequences of its deficiency are yet to be identified.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Role of the Polymeric Ig Receptor in Mucosal B Cell Homeostasis

Uren

Johansen

Wijburg

et al. 2003

The Journal of Immunology

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“…However, cervically colonized women seem to have another distribution of antibodies to different GBS epitopes than rectally colonized women, and these differences might be important for eradication of colonization. Mucosal antibodies may protect against invasive infections but still permit colonization, which is the case for commensal bacteria in the gut [31,32]. On the other hand, they may eradicate microbes from the mucosal surface, as demonstrated for Respiratory Syncytial Virus (RSV) and Haemophilus influenzae in the respiratory tract [33,34], or Vibrio cholera, Helicobacter felis and Salmonella typhimurium in the gut [35][36][37].…”

Section: Discussionmentioning

confidence: 99%

Cervical Secretions in Pregnant Women Colonized Rectally with Group B Streptococci have High Levels of Antibodies to Serotype III Polysaccharide Capsular Antigen and Protein R

et al. 1998

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Immunol 1998;47:179-188 Group B streptococci (GBS) colonizing the female genital tract will often infect newborn infants during delivery. In 200 pregnant women studied, 14% were colonized with GBS in the cervix, 12% in the rectum, and 9% in both cervix and rectum. We have previously reported that antibody levels to GBS serotypes Ia, II, and III in sera and cervical secretions were increased in women colonized in the rectum and/or cervix, when analyzed by a whole-cell ELISA. Here, we report the levels of antibodies to GBS serotype III capsular polysaccharide antigen (CPS III) and to protein antigen R 4 , which are present in most GBS III strains. Compared to culture-negative women, the group of women colonized rectally had markedly elevated levels of immunoglobulin (Ig)A and IgG antibodies in cervical secretions to both CPS III and protein R 4 (P < 0.01 and P < 0.001, respectively). In sera, the corresponding differences between culture-negative and culture-positive women were less pronounced, or not present. In contrast to antibody levels to whole-cell GBS, antibody levels to CPS III and protein R 4 in cervical secretions were not significantly increased in women colonized only in the cervix, except that IgA antibodies to protein R 4 were slightly elevated (P < 0.05). These findings suggest that capsular type-specific polysaccharides and protein R 4 in a mucosal vaccine might induce protective antibodies against GBS colonization of the uterine cervix.

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“…Similar to SIgA, IgG in mucosal secretions has been reported to actively participate in the host defense against specific pathogens (8,10). In previous studies, IgG in mucosal compartments was frequently found in such pathogenic conditions as inflammatory bowel disease (11,12) and intestinal allergy (13). Mucosa-associated IgG Ab has long been known to be the only class of Ab that is actively transferred from mother to offspring to confer short-term passive immunity (14).…”

mentioning

confidence: 99%

IFN-γ Secreted by CD103+ Dendritic Cells Leads to IgG Generation in the Mesenteric Lymph Node in the Absence of Vitamin A

Chang

Cha

Chang

et al. 2011

The Journal of Immunology

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Although the induction mechanism of secretory IgA has been well studied, that of IgG in the mucosal compartments is not well understood. In this study, vitamin A deficiency was convincingly shown to be associated with increased IgG in serum and intestinal fluid. We found increased numbers of IgG-secreting B cells in the lamina propria of the small intestine and mesenteric lymph node (MLN) of vitamin A-deficient (VAD) mice. Of note, IFN-γ secreted by MLN dendritic cells (DCs) was significantly augmented in VAD mice, unlike control mice, and CD103+ DCs were the main subsets to secrete IFN-γ. The aberrant increase of IgG in VAD mice can be ascribable to IFN-γ, because IFN-γ−/− VAD mice have normal IgG levels and the addition of rIFN-γ increased IgG production by B cells cocultured with MLN DCs from IFN-γ−/− VAD mice. Oral feeding of antibiotics resulted in significant reduction of IgG in VAD mice, indicating a critical role for altered commensal bacteria for IgG class-switching recombination in the absence of vitamin A. Collectively, vitamin A deficiency provokes the generation of IFN-γ–secreting CD103+ DCs, which may be a critical regulator for IgG generation in the MLN.

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Mucosal antibodies in inflammatory bowel disease are directed against intestinal bacteria.

Abstract: In contrast with normal subjects where IgA is the main immunoglobulin in the intestine, patients with active inflammatory bowel disease (IBD)

Cited by 395 publications

References 40 publications

Role of the Polymeric Ig Receptor in Mucosal B Cell Homeostasis

Role of the Polymeric Ig Receptor in Mucosal B Cell Homeostasis

Cervical Secretions in Pregnant Women Colonized Rectally with Group B Streptococci have High Levels of Antibodies to Serotype III Polysaccharide Capsular Antigen and Protein R

IFN-γ Secreted by CD103+ Dendritic Cells Leads to IgG Generation in the Mesenteric Lymph Node in the Absence of Vitamin A

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