Clinical significance of soluble immunoglobulins A and G and their coated bacteria in feces of patients with inflammatory bowel disease

Lin, Ritian; Chen, Hongwei; Shu, Weigang; Sun, Mingming; Fang, Leilei; Shi, Yanhong; Pang, Zhi; Wu, Wei; Liu, Zhanju

doi:10.1186/s12967-018-1723-0

Cited by 51 publications

(62 citation statements)

References 34 publications

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“…Inflammation in IBD in humans is thought to be mediated by both cellular and humoral immune mechanisms [6–8]. Increasingly, studies in IBD in humans (e.g., Crohn’s disease, ulcerative colitis) have focused on the role of immune responses targeted to gut bacteria, as opposed to immune responses targeting gut tissues or dietary antigens [9–12].…”

Section: Introductionmentioning

confidence: 99%

“…Studies in humans with IBD have found significantly increased numbers of fecal bacteria with bound IgG, especially in patients with Crohn’s disease (CD) and ulcerative colitis (UC) [12, 18, 19]. It has also been shown in some cases that IBD patients have greater numbers of IgA + bacteria [12, 20]. Interestingly, studies found that the IgG and IgA antibodies preferentially bound to certain pathogenic bacteria in CD patients, including Clostridium coccoides , E .…”

Section: Introductionmentioning

confidence: 99%

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Humoral immune responses against gut bacteria in dogs with inflammatory bowel disease

et al. 2019

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Inflammatory bowel disease (IBD) in dogs is associated with clinical signs of intestinal dysfunction, as well as abnormal lymphocytic and myeloid cell infiltrates in the small and/or large intestine. Thus, in many respects IBD in dogs resembles IBD in humans. However, the factors that trigger intestinal inflammation in dogs with IBD are not well understood and have been variously attributed to immune responses against dietary antigens or intestinal antigens. Previous studies in humans with IBD have documented increased production of IgG and IgA antibodies specific to intestinal bacteria, and this abnormal immune response has been linked to disease pathogenesis. Therefore, we investigated the humoral immune response against gut bacteria in dogs with IBD, using flow cytometry to quantitate IgG and IgA binding. Studies were also done to investigate the source of these antibodies (locally produced versus systemic production) and whether greater antibody binding to bacteria is associated with increased inflammatory responses. We found that dogs with IBD had significantly higher percentages and overall amounts of IgG bound to their intestinal bacteria compared to healthy dogs. Similarly, significantly higher percentages of bacteria were IgA + bacteria were also found in dogs with IBD. Serum antibody recognition of gut bacteria was not different between healthy dogs and dogs with IBD, suggesting that anti-bacterial antibodies were primarily produced locally in the gut rather than systemically. Importantly, bacteria in the Actinobacteria phylum and in particular the genus Collinsella had significantly greater levels of antibody binding in dogs with IBD. Based on these findings, we concluded that antibody binding to commensal gut bacteria was significantly increased in dogs with IBD, that particular phyla were preferential targets for gut antibodies, and that anti-bacterial antibody responses may play an important role in regulating gut inflammation.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Humoral immune responses against gut bacteria in dogs with inflammatory bowel disease

et al. 2019

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“…Opsonization of gut bacteria with IgA even converts anti-inflammatory intestinal CD103 + DCs to a proinflammatory phenotype, which protects against invading pathogens, but might also result in chronic inflammation 5 . Evidence exists that serum IgA contributes to autoimmune diseases, such as inflammatory bowel disease 6,7 , autoimmune skin blistering diseases 8,9 , or rheumatoid arthritis (RA) [10][11][12] as well as to transplant rejection 13 . In addition, IgA has gained interest as a therapeutic antibody against cancer cells, as it activates neutrophilmediated antibody-dependent cellular cytotoxicity better than IgG 14,15 .…”

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confidence: 99%

IgA subclasses have different effector functions associated with distinct glycosylation profiles

et al. 2020

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Monomeric serum immunoglobulin A (IgA) can contribute to the development of various autoimmune diseases, but the regulation of serum IgA effector functions is not well defined. Here, we show that the two IgA subclasses (IgA1 and IgA2) differ in their effect on immune cells due to distinct binding and signaling properties. Whereas IgA2 acts pro-inflammatory on neutrophils and macrophages, IgA1 does not have pronounced effects. Moreover, IgA1 and IgA2 have different glycosylation profiles, with IgA1 possessing more sialic acid than IgA2. Removal of sialic acid increases the pro-inflammatory capacity of IgA1, making it comparable to IgA2. Of note, disease-specific autoantibodies in patients with rheumatoid arthritis display a shift toward the pro-inflammatory IgA2 subclass, which is associated with higher disease activity. Taken together, these data demonstrate that IgA effector functions depend on subclass and glycosylation, and that disturbances in subclass balance are associated with autoimmune disease.

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“…This observation suggests that AIEC bacteria can be targeted by SIgA in an inflammatory context and that stimulating this pathway could lead to a decrease AIEC load in CD patients. The levels of soluble IgA and the percentage of IgA-coated bacteria strikingly increases in feces of IBD patients and correlates with the disease activity 55 – 57 . This could be related to an over-activation of IgA-producing mucosal B-cells in response to bacterial stimulus of the adaptive immune system.…”

Section: Discussionmentioning

confidence: 99%

Methyl-donor supplementation prevents intestinal colonization by Adherent-Invasive E. coli in a mouse model of Crohn’s disease

Gimier

Chervy

Agus

et al. 2020

Sci Rep

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Deficiencies in methyl-donor molecules (folate, B12 vitamin), DNA methylation alteration and high prevalence of Adherent-invasive Escherichia coli (AIEC) are frequently observed in Crohn's disease (CD) patients. Aiec bacteria adhere to the enterocytes through abnormally expressed carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) glycoprotein on host cells. This work aims at studying the relationship between methyl-donor molecules and AIEC-induced intestinal inflammatory response. CEABAC10 mice, a mouse model of CD, were fed a control or Methyl-donor Supplemented diet (MS diet). CEACAM6 promoter was hypermethylated in intestinal epithelial cells from mice fed an MS diet, which was associated with a significant decrease in CEACAM6 expression. transcriptomic analysis revealed increased expression of anti-microbial peptides, increase in HSP70 gene family expression and a decreased expression of inflammatory marker Calprotectin upon MS diet, associated to a lower ability of AIEC bacteria to colonize gut mucosa. We observed in a cohort of CD patients that serum folate concentration was inversely correlated to Crohn's disease endoscopic index of severity and to fecal inflammatory markers. This study demonstrates that methyl-donor supplementation through the diet induces a specific intestinal micro-environment limiting pathobiont colonization of the gut. Clinicians may wish to consider methyl-donor supplementation for methyl-donor deficient CD patients. Abbreviations AIEC Adherent-Invasive Escherichia coli BSA Bovine serum albumin CD Crohn's disease CDEIS Crohn's disease endoscopic index of severity CEABAC10 Carcinoembryonic antigen bacterial artificial chromosome 10 CEACAM Carcinoembryonic antigen-related cell adhesion molecule FBS Fetal bovine serum

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Clinical significance of soluble immunoglobulins A and G and their coated bacteria in feces of patients with inflammatory bowel disease

Cited by 51 publications

References 34 publications

Humoral immune responses against gut bacteria in dogs with inflammatory bowel disease

Humoral immune responses against gut bacteria in dogs with inflammatory bowel disease

IgA subclasses have different effector functions associated with distinct glycosylation profiles

Methyl-donor supplementation prevents intestinal colonization by Adherent-Invasive E. coli in a mouse model of Crohn’s disease

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