Selective IgA deficiency in humans is associated with reduced gut microbial diversity

Jørgensen, Silje Fjellgård; Holm, Kristian; Macpherson, Magnhild Eide; Storm-Larsen, Christopher; Kummen, Martin; Fevang, Børre; Aukrust, Pål; Hov, Johannes R.

doi:10.1016/j.jaci.2019.01.019

Cited by 33 publications

(32 citation statements)

References 16 publications

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“…Patients with isolated IgA deficiency have been found to have lower frequencies of T R cells, especially in those patients with IgA deficiency and autoimmune disease (104). They have also been found to have reduced gut microbial diversity (105). Separately, a feedback loop has been described whereby healthy microbiota stimulate T R cells and leads to the formation of germinal centers and IgA, which in turn maintains a healthy microbiome (106).…”

Section: Microbiome In Cvid and Autoimmunitymentioning

confidence: 99%

Current Understanding and Recent Developments in Common Variable Immunodeficiency Associated Autoimmunity

Gereige

Maglione

2019

Front. Immunol.

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Common variable immunodeficiency (CVID) is the most prevalent symptomatic primary immunodeficiency and comprises a group of disorders with similar antibody deficiency but a myriad of different etiologies, most of which remain undefined. The variable aspect of CVID refers to the approximately half of patients who develop non-infectious complications in addition to heightened susceptibility to infection. The pathogenesis of these complications is poorly understood and somewhat counterintuitive because these patients that are defined by their immune futility simultaneously have elevated propensity for autoimmune disease. There are numerous aspects of immune dysregulation associated with autoimmunity in CVID that have only begun to be studied. These findings include elevations of T helper type 1 and follicular helper T cells and B cells expressing low levels of CD21 as well as reciprocal decreases in regulatory T cells and isotype-switched memory B cells. Recently, advances in genomics have furthered our understanding of the fundamental biology underlying autoimmunity in CVID and led to precision therapeutic approaches. However, these genetic etiologies are also associated with clinical heterogeneity and incomplete penetrance, highlighting the fact that continued research efforts remain necessary to optimize treatment. Additional factors, such as commensal microbial dysbiosis, remain to be better elucidated. Thus, while recent advances in our understanding of CVID-associated autoimmunity have been exciting and substantial, these current scientific advances must now serve as building blocks for the next stages of discovery.

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Section: Microbiome In Cvid and Autoimmunitymentioning

confidence: 99%

Current Understanding and Recent Developments in Common Variable Immunodeficiency Associated Autoimmunity

Gereige

Maglione

2019

Front. Immunol.

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“…2 Thus, >80% of patients with CGD will present with autoinflammatory manifestations before reaching adulthood. 2 We and others have shown that patients with CGD with inflammatory manifestations present a dysregulated inflammasome activation in macrophage/ phagocytic cells 3,4 through pathophysiologic mechanisms that remain unclear. Interestingly, female carriers of CYBB deficiency also present with inflammatory condition and immune defect albeit to a lesser degree depending on chromosome X inactivation.…”

Section: Antibody-coated Microbiota In Nasopharynx Of Healthy Individmentioning

confidence: 99%

“…sIgA is the predominant antibody isotype in human nasopharyngeal secretions, and it is assumed that most sIgA targets the resident commensal microbiota, inhibiting their penetration via agglutination within the mucus layer and thereby reinforcing commensalism and increasing microbiota diversity. 3 High-affinity sIgA appears to neutralize microbial toxins and invasive pathogens in the absence of complement fixation. 3 Interestingly, Fadlallah et al 4 reported recently that patients with selective IgA deficiency (SIgADef) display mild dysbiosis, with expansion of some pathobiont species in their feces as compared with in healthy controls, although these patients are not abnormally susceptible to intestinal infections.…”

Section: Antibody-coated Microbiota In Nasopharynx Of Healthy Individmentioning

confidence: 99%

“…3 High-affinity sIgA appears to neutralize microbial toxins and invasive pathogens in the absence of complement fixation. 3 Interestingly, Fadlallah et al 4 reported recently that patients with selective IgA deficiency (SIgADef) display mild dysbiosis, with expansion of some pathobiont species in their feces as compared with in healthy controls, although these patients are not abnormally susceptible to intestinal infections. On the other hand, recurrent pulmonary infections constitute the most prevalent comorbidity in patients with SIgADef, 4 suggesting that sIgA may have tissue-specific roles in immune defense, especially in the respiratory tract.…”

Section: Antibody-coated Microbiota In Nasopharynx Of Healthy Individmentioning

confidence: 99%

“…These results suggest that under homeostatic conditions, sIgA binds to a broad repertoire of bacteria present in nasopharyngeal microbiota, including both commensals and pathobionts. 3 Most patients with SIgADef have a mild clinical phenotype, 4 which may result from the ability of other Ig isotypes to functionally replace IgA. Increased IgD 1 IgM -B-cell populations and increased soluble IgD levels have been described in healthy human upper respiratory mucosa.…”

Section: Antibody-coated Microbiota In Nasopharynx Of Healthy Individmentioning

confidence: 99%

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Antibody-coated microbiota in nasopharynx of healthy individuals and IVIg-treated patients with hypogammaglobulinemia

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Charbit

Lenoir

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Gut microbiota shape B cell in health and disease settings

Wang

Chu

2021

Journal of Leukocyte Biology

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Recent accumulating evidence supports the hypothesis that the intricate interaction between gut microbiota and the immune system profoundly affects health and disease in humans and mice. In this context, microbiota plays an important role in educating and shaping the host immune system which, in turn, regulates gut microbiota diversity and function to maintain homeostasis. Studies have demonstrated that intestinal microbiota participates in shaping B cells in health and disease settings. Herein, we review the recent progress in understanding how microbiota regulates B-cell development, focusing on early-life B-cell repertoire generation in GALT and how microbial products, including microbial antigens and metabolites, affect B-cell activation and differentiation to ultimately regulate B-cell function. We also discuss the interaction between gut microbiota and B cells under pathogenic conditions and highlight new approaches that can be applied to treat various diseases.

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Selective IgA deficiency in humans is associated with reduced gut microbial diversity

Cited by 33 publications

References 16 publications

Current Understanding and Recent Developments in Common Variable Immunodeficiency Associated Autoimmunity

Current Understanding and Recent Developments in Common Variable Immunodeficiency Associated Autoimmunity

Antibody-coated microbiota in nasopharynx of healthy individuals and IVIg-treated patients with hypogammaglobulinemia

Gut microbiota shape B cell in health and disease settings

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