ArticleThe Journal of clinical investigation1996
A defective Vkappa A2 allele in Navajos which may play a role in increased susceptibility to haemophilus influenzae type b disease.
Article in The Journal of clinical investigation, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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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.
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Who cites it
48 citing papers in PubMed, 107 citations in OpenAlex.
- Article
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- Addressing Technical Pitfalls in Pursuit of Molecular Factors That Mediate Immunoglobulin Gene Regulation.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Resolving haplotype variation and complex genetic architecture in the human immunoglobulin kappa chain locus in individuals of diverse ancestry.Genes and immunity · 2024Article
- Human immunoglobulin gene allelic variation impacts germline-targeting vaccine priming.NPJ vaccines · 2024Article
- Enhancers within the Ig V Gene Region Orchestrate Chromatin Topology and Regulate V Gene Rearrangement Frequency to Shape the B Cell Receptor Repertoire Specificities.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Genetic variation in the immunoglobulin heavy chain locus shapes the human antibody repertoire.Nature communications · 2023Article
- Adaptive immune receptor genotyping using theFrontiers in immunology · 2023Article
- Analysis of IGH allele content in a sample group of rheumatoid arthritis patients demonstrates unrevealed population heterogeneity.Frontiers in immunology · 2023Article
- Immunoglobulin germline gene variation and its impact on human disease.Genes and immunity · 2021Review
- Igh Locus Polymorphism May Dictate Topological Chromatin Conformation and V Gene Usage in the Ig Repertoire.Frontiers in immunology · 2021Review
- Germline immunoglobulin genes: disease susceptibility genes hidden in plain sight?Current opinion in systems biology · 2020Article
- B Cell Disorders in Children: Part II.Current allergy and asthma reports · 2020Review
- Weaving the Strands of Life (Human biology · 2020Review
- Sequence-dependent dynamics of synthetic and endogenous RSSs in V(D)J recombination.Nucleic acids research · 2020Article
- A Novel Framework for Characterizing Genomic Haplotype Diversity in the Human Immunoglobulin Heavy Chain Locus.Frontiers in immunology · 2020Article
- B Cells Carrying Antigen Receptors Against Microbes as Tools for Vaccine Discovery and Design.Current topics in microbiology and immunology · 2020Review
- Mercury Exposure and Poor Nutritional Status Reduce Response to Six Expanded Program on Immunization Vaccines in Children: An Observational Cohort Study of Communities Affected by Gold Mining in the Peruvian Amazon.International journal of environmental research and public health · 2019Observational
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The antibody response to H. influenzae type b (Hib) is pauciclonal, and is dominated by antibodies using the VkappaA2 gene. Navajos have a 5-10-fold increased incidence of Hib disease compared with control populations. We hypothesized that a polymorphism in one of the genes in this oligoclonal response may lead to increased disease susceptibility. Since the predominant A2+ anti-Hib antibodies have high avidity for Hib and can be unmutated, the A2 Vkappa gene was analyzed. Over half of the Navajos studied, but only one control individual, had a new allele of A2, termed A2b, with three changes from the published A2 germline sequence. One of the changes was in the recombination signal sequence, suggesting that the A2b allele might not undergo V-J rearrangement very frequently. This possibility was confirmed by analyzing the relative frequency of non-productive A2 rearrangements in A2a/b heterozygous Navajos. Many fewer A2b rearrangements were observed, showing that the A2b allele is defective in its ability to undergo rearrangement. The prevalence of this allele in Navajos may play a role in their increased susceptibility to invasive Hib disease. If so, it would underscore the importance of the germline Ig repertoire for protective antibody responses to pathogenic bacteria in unimmunized children.
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Registered trials
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