ArticleScience immunology2023
IgA deficiency destabilizes homeostasis toward intestinal microbes and increases systemic immune dysregulation.
Article in Science immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 2 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
57 citing papers in PubMed, 2 syntheses or guidelines pooled it, 67 citations in OpenAlex.
- Mucosal immune response in biology, disease prevention and treatment.Signal transduction and targeted therapy · 2025Pooled it
- Leveraging pleiotropy identifies common-variant associations with selective IgA deficiency.Clinical immunology (Orlando, Fla.) · 2024Pooled it
- Probiotic-induced enrichment ofGut microbes · 2025Trial
- IgA Deficiency Exacerbates an Animal Model of Multiple Sclerosis Induced with Theiler's Virus.Cells · 2026Article
- Oral PHGG ameliorates atopic dermatitis-like dermatitis with concurrent modulation of colonic IgA and cecal microbiota: implications for the gut-skin axis.Journal of the science of food and agriculture · 2026Article
- Anisakiasis: A Decade of Molecular and Diagnostic Advancements (2015-2026).International journal of molecular sciences · 2026Review
- Antibody subclass deficiency accelerates tumorigenesis in genetically engineered mouse models of pancreatic cancer.JCI insight · 2026Article
- Gut microbiota and aging: current understanding and future perspectives.Molecular biomedicine · 2026Review
- Clinical characteristics, risk factors, and pathogen spectrum of mixed infections in children withMicrobiology spectrum · 2026Article
- Bifidobacterium-driven immunoglobulin A production in pediatric patients with IgA deficiency and recurrent respiratory tract infections.Microbiome · 2026Article
- Multi-omics reveal vitamin D regulation of immune-gut microbiome interactions and tolerogenic pathways in inflammatory bowel disease.Cell reports. Medicine · 2026Article
- Immunomodulatory Role of Milk on Gut Microbiota: Implications for Enhancing Oral Vaccine Efficacy.Probiotics and antimicrobial proteins · 2026Review
- Loss of Bone Marrow β1/β2-Adrenergic Receptors Reprograms Host-Microbiota Interactions and Protects Against Diet-Induced Obesity.bioRxiv : the preprint server for biology · 2026Article
- IgA defects in CVID lead to bacterial translocation, increased serum γ-interferon, and BAFF.Journal of human immunity · 2026Article
- Gut virome dynamics: from commensal to critical player in health and disease.Nature reviews. Gastroenterology & hepatology · 2026Review
- Article
- Nutritional needs of non-essential amino acids for intestinal health and growth performance of nursery pigs fed diets without soybean meal.Journal of animal science · 2026Article
- Mechanisms of inflammation in premature ovarian insufficiency and advances in therapeutic studies.Frontiers in immunology · 2026Review
- Gut microbiota and osteoarthritis: mechanisms and translation.Frontiers in immunology · 2026Review
- Mechanistic remodeling and immunoregulatory functions of the B cell-humoral immunity axis in inflammatory bowel disease.Frontiers in immunology · 2026Review
Corrections and comments
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Authors and funding
19 authors at 3 institutions in 1 country.
Funding
Abstract
The ability of most patients with selective immunoglobulin A (IgA) deficiency (SIgAD) to remain apparently healthy has been a persistent clinical conundrum. Compensatory mechanisms, including IgM, have been proposed, yet it remains unclear how secretory IgA and IgM work together in the mucosal system and, on a larger scale, whether the systemic and mucosal anti-commensal responses are redundant or have unique features. To address this gap in knowledge, we developed an integrated host-commensal approach combining microbial flow cytometry and metagenomic sequencing (mFLOW-Seq) to comprehensively define which microbes induce mucosal and systemic antibodies. We coupled this approach with high-dimensional immune profiling to study a cohort of pediatric patients with SIgAD and household control siblings. We found that mucosal and systemic antibody networks cooperate to maintain homeostasis by targeting a common subset of commensal microbes. In IgA-deficiency, we find increased translocation of specific bacterial taxa associated with elevated levels of systemic IgG targeting fecal microbiota. Associated features of immune system dysregulation in IgA-deficient mice and humans included elevated levels of inflammatory cytokines, enhanced follicular CD4 T helper cell frequency and activation, and an altered CD8 T cell activation state. Although SIgAD is clinically defined by the absence of serum IgA, the symptomatology and immune dysregulation were concentrated in the SIgAD participants who were also fecal IgA deficient. These findings reveal that mucosal IgA deficiency leads to aberrant systemic exposures and immune responses to commensal microbes, which increase the likelihood of humoral and cellular immune dysregulation and symptomatic disease in patients with IgA deficiency.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.