Trial reportBlood2014
IRAK-4 and MyD88 deficiencies impair IgM responses against T-independent bacterial antigens.
Trial report in Blood, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
37 citing papers in PubMed, 66 citations in OpenAlex.
- Safety, tolerability, pharmacokinetics, and pharmacodynamics of PF-06650833, a selective interleukin-1 receptor-associated kinase 4 (IRAK4) inhibitor, in single and multiple ascending dose randomized phase 1 studies in healthy subjects.Arthritis research & therapy · 2019Trial
- Epigenetic signatures mark early peripheral human B lineage bifurcation and differential transcriptional profiles in mature populations.Nature communications · 2026Article
- Cutaneous Manifestations of Inborn Errors of Immunity: Clinical Clues to Immune Disorders.Medicina (Kaunas, Lithuania) · 2026Review
- Review
- Trimming the fat: a brief review of lipids at the host-pathogen interface.Infection and immunity · 2025Review
- MyD88 signalling in B cells and antibody responses during Oropouche virus-induced neurological disease in mice.EBioMedicine · 2025Article
- Learning from inborn errors of immunity and secondary immune deficiencies about vaccine immunogenicity, efficacy, and safety.Clinical and experimental immunology · 2025Review
- Three Unrelated Patients of Roma Ethnicity from a Single Center Carrying the Same Deletion inLife (Basel, Switzerland) · 2024Article
- In Retrospect: Root-Cause Analysis of Structure-Activity Relationships in IRAK4 Inhibitor Zimlovisertib (PF-06650833).ACS medicinal chemistry letters · 2024Article
- Gut-associated lymphoid tissue: a microbiota-driven hub of B cell immunity.Trends in immunology · 2024Review
- B cell diversification in gut-associated lymphoid tissues: From birds to humans.The Journal of experimental medicine · 2023Article
- Impact of MyD88 Deficiency on Innate Immune Function in COVID-19 Infection and Allotransplantation.Transplantation · 2023Article
- Identification of a heterozygous pathogenic variant in IRAK4 in an adult patient with pneumococcal sepsis, monoclonal gammopathy of uncertain significance, and idiopathic systemic capillary leak syndrome.The journal of allergy and clinical immunology. Global · 2023Article
- Case of Fatal Meningitis in an Adult Patient with IRAK4 Deficiency.Journal of clinical immunology · 2023Article
- The tumor immune microenvironment of nasopharyngeal carcinoma after gemcitabine plus cisplatin treatment.Nature medicine · 2023Article
- Human intestinal B cells in inflammatory diseases.Nature reviews. Gastroenterology & hepatology · 2023Review
- T-independent responses to polysaccharides in humans mobilize marginal zone B cells prediversified against gut bacterial antigens.Science immunology · 2023Article
- B cells in human lymphoid structures.Clinical and experimental immunology · 2022Review
- E6020, a TLR4 Agonist Adjuvant, Enhances Both Antibody Titers and Isotype Switching in Response to Immunization with Hapten-Protein Antigens and Is Diminished in Mice with TLR4 Signaling Insufficiency.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Convergence of cytokine dysregulation and antibody deficiency in common variable immunodeficiency with inflammatory complications.The Journal of allergy and clinical immunology · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 6 institutions in 4 countries.
Funding
Abstract
IRAK-4 and MyD88 deficiencies impair interleukin 1 receptor and Toll-like receptor (TLR) signaling and lead to heightened susceptibility to invasive bacterial infections. Individuals with these primary immunodeficiencies have fewer immunoglobulin M (IgM)(+)IgD(+)CD27(+) B cells, a population that resembles murine splenic marginal zone B cells that mount T-independent antibody responses against bacterial antigens. However, the significance of this B-cell subset in humans is poorly understood. Using both a 610 carbohydrate array and enzyme-linked immunosorbent assay, we found that patients with IRAK-4 and MyD88 deficiencies have reduced serum IgM, but not IgG antibody, recognizing T-independent bacterial antigens. Moreover, the quantity of specific IgM correlated with IgM(+)IgD(+)CD27(+) B-cell frequencies. As with mouse marginal zone B cells, human IgM(+)CD27(+) B cells activated by TLR7 or TLR9 agonists produced phosphorylcholine-specific IgM. Further linking splenic IgM(+)IgD(+)CD27(+) B cells with production of T-independent IgM, serum from splenectomized subjects, who also have few IgM(+)IgD(+)CD27(+) B cells, had reduced antibacterial IgM. IRAK-4 and MyD88 deficiencies impaired TLR-induced proliferation of this B-cell subset, suggesting a means by which loss of this activation pathway leads to reduced cell numbers. Thus, by bolstering the IgM(+)IgD(+)CD27(+) B-cell subset, IRAK-4 and MyD88 promote optimal T-independent IgM antibody responses against bacteria in humans.
Indexed as
Identifiers
What OpenQuestion holds
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.