Immunogenetics articles within Nature Communications

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  • Article
    | Open Access

    Asthma is a common allergic airway disease with significant inter-individual heterogeneity. Here, Olafsdottir et al. report a genome-wide meta-analysis of two large population-based cohorts to identify sequence variants that associate with asthma risk and perform follow-up functional analyses on a protective loss-of-function variant in TNFRSF8.

    • Thorunn A. Olafsdottir
    • , Fannar Theodors
    •  & Kari Stefansson

  • Article
    | Open Access

    Systemic autoinflammatory syndromes such as cryopyrin-associated periodic syndrome (CAPS) are rare and often involve genes related to the inflammasome. Here, the authors report a syndrome characterised by systemic inflammation and cold-induced urticarial rash associated with a Factor XII-activating mutation.

    • Jörg Scheffel
    • , Niklas A. Mahnke
    •  & Karoline Krause

  • Article
    | Open Access

    Four genome-wide associated loci are currently known for malaria susceptibility. Here, the authors expand on earlier work by combining data from 11 malaria-endemic countries and additional population sequencing informing an African-enriched imputation reference panel, with findings including a previously unreported association on chromosome 6.

    • Gavin Band
    • , Quang Si Le
    •  & Dominic P. Kwiatkowski

  • Article
    | Open Access

    Metabolic syndrome is characterized by complex phenotypes that increases the risk of cardiovascular disease and type 2 diabetes. Here the authors’ integrative network analysis suggests BTK inhibitor ibrutinib to be a promising treatment through its obesity-associated inflammation lowering effect.

    • Karla Misselbeck
    • , Silvia Parolo
    •  & Corrado Priami

  • Article
    | Open Access

    Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare inflammatory disorder characterised by asthma, eosinophilia and vasculitis. Here, the authors describe a genome-wide association study of EGPA that reveals clinical and genetic differences between subgroups stratified by autoantibody status (ANCA).

    • Paul A Lyons
    • , James E Peters
    •  & Kenneth G. C. Smith

  • Article
    | Open Access

    MHC-I-induced signalling of various natural killer (NK) inhibitory receptors is critical for regulation NK cell education, but clear genetic evidence is still lacking. Here the authors generate multiple lines of mice differentially deficient in Ly49 family and/or NKG2A NK receptors, and find that self-MHCI specific Ly49 members and NKG2A synergize to regulate NK education.

    • Xiaoqian Zhang
    • , Jin Feng
    •  & Zhongjun Dong

  • Article
    | Open Access

    Roquin-1 is a posttranscriptional regulator that controls the expression of many immune-related genes such as ICOS and TNFA. Here, the authors report a homozygous R688* loss of function mutation in Roquin-1 in a patient with syndromic uncontrolled hyperinflammation associated with immune cell activation and hypercytokinemia.

    • S. J. Tavernier
    • , V. Athanasopoulos
    •  & F. Haerynck

  • Article
    | Open Access

    Interleukin-7 (IL-7) is a central cytokine in T cell homeostasis. Here the authors show that allelic variation at rs6897932, an autoimmune GWAS risk allele at IL7R, regulates surface and soluble IL-7R in stimulated monocytes, indicating a function of monocytes in IL-7-related autoimmunity.

    • Hussein Al-Mossawi
    • , Nicole Yager
    •  & Benjamin P. Fairfax

  • Article
    | Open Access

    Sexual dimorphism is observed frequently in immune disorders, but the underlying insights are still unclear. Here the authors analyze transcriptome and epigenome changes induced by interferon in various mouse immune cell types, and find only a restricted set of sexual dimorphism genes in innate immunity and macrophages.

    • Shani Talia Gal-Oz
    • , Barbara Maier
    •  & Tal Shay

  • Article
    | Open Access

    Demethylation of the genome is found in cancer. Here, the authors show that genomic demethylation entails changes in promoter methylation and gene expression associated with immune escape and suggest that the epigenetic alterations may be an important determinant of responses to immunotherapy.

    • Hyunchul Jung
    • , Hong Sook Kim
    •  & Jung Kyoon Choi

  • Article
    | Open Access

    Between 5 and 15% of latent Mycobacterium tuberculosis infections develop into active tuberculosis (TB). Here, Luo et al. report a genome-wide association study for early TB progression in a total of 4002 active TB cases and their household contacts in Peru and they identify a locus on 3q23 in which ATP1B3 is mapped as the likely causal gene.

    • Yang Luo
    • , Sara Suliman
    •  & Soumya Raychaudhuri

  • Article
    | Open Access

    Severe cutaneous adverse reactions (SCAR) is a T cell-mediated, potentially lethal drug hypersensitivity (DH). Here, the authors identify a carbamazepine-specific TCR common among patients with carbamazepine-induced SCAR that confers SCAR-like pathology in mice upon carbamazepine exposure, thereby implicating specific TCRs in DH etiology.

    • Ren-You Pan
    • , Mu-Tzu Chu
    •  & Shuen-Iu Hung

  • Article
    | Open Access

    Statistical fine-mapping to pinpoint likely causal variants in a genomic region is complicated by linkage disequilibrium (LD). Here, Asimit et al. compare stepwise and stochastic approaches to fine-mapping and propose a Bayesian multinomial stochastic search method which they apply to six immune-mediated diseases.

    • Jennifer L. Asimit
    • , Daniel B. Rainbow
    •  & Chris Wallace

  • Article
    | Open Access

    Function-altering variants of immune-related genes cause rare autoimmune syndromes, whereas their contribution to common autoimmune diseases remains uncharacterized. Here the authors show that rare variants of lupus-associated genes are present in the majority of lupus patients and healthy controls, but only the variants found in lupus patients alter gene function.

    • Simon H. Jiang
    • , Vicki Athanasopoulos
    •  & Carola G. Vinuesa

  • Article
    | Open Access

    Streptococcus pneumoniae is a causative agent of meningitis and bacteremia. In a combined pathogen and host GWAS, Lees et al. find that host genetic variation is associated with both susceptibility and severity of pneumococcal meningitis, and specific bacterial genetic variation associated with susceptibility.

    • John A. Lees
    • , Bart Ferwerda
    •  & Diederik van de Beek

  • Article
    | Open Access

    The use of functional genomics in primary immune cells has been limited by inefficient vector delivery and risk of perturbing cell states. Here the authors present CHimeric IMmune Editing (CHIME) for in vivo evaluation of gene function and pooled screening approaches.

    • Martin W. LaFleur
    • , Thao H. Nguyen
    •  & Arlene H. Sharpe

  • Article
    | Open Access

    Frontal fibrosing alopecia (FFA) features lichenoid cutaneous inflammation and scarring hair loss. Here, Tziotzios et al. identify four genetic loci associated with FFA by GWAS followed by Bayesian fine-mapping, co-localisation and HLA imputation which highlights HLA-B*07:02 as a risk factor.

    • Christos Tziotzios
    • , Christos Petridis
    •  & John A. McGrath

  • Article
    | Open Access

    Oral ulcerations are sores of the mucous membrane of the mouth and highly prevalent in the population. Here, in a genome-wide association study, the authors identify 97 loci associated with mouth ulcers highlighting genes involved in T cell-mediated immunity and TH1 responses.

    • Tom Dudding
    • , Simon Haworth
    •  & Nicholas J. Timpson

  • Article
    | Open Access

    The burden of asthma varies between ancestries, but GWAS have so far focused on mainly European ancestry populations. Here, Daya et al. perform GWAS for asthma in 14,654 individuals of African ancestry and, besides confirming previously known loci, identify two potentially African ancestry-specific loci.

    • Michelle Daya
    • , Nicholas Rafaels
    •  & Maria Yazdanbakhsh

  • Article
    | Open Access

    High-throughput sequencing and analyzes of antibody repertoire provide important information on immune responses, but current methodologies are limited in sequence assembly precision and haplotype inference validity. Here the authors propose a new Bayesian haplotyping method, and attest its broad application with a large, multi-individual dataset.

    • Moriah Gidoni
    • , Omri Snir
    •  & Gur Yaari

  • Article
    | Open Access

    Host genetics modulates gut microbiota composition, which in turn affects host health, but little is known about the specific genes involved. Here, Berg et al. show that TGFβ/BMP immune signalling affects abundance and function of commensal Enterobacter species in C. elegans.

    • Maureen Berg
    • , David Monnin
    •  & Michael Shapira

  • Article
    | Open Access

    GWAS have led to the identification of 49 genetic loci associated with vitiligo. Here, the authors observe a bimodal distribution of age-of-onset and find a novel genetic locus specifically associated with early-onset vitiligo, located in a regulatory element in the MHC class II region.

    • Ying Jin
    • , Genevieve H. L. Roberts
    •  & Richard A. Spritz

  • Article
    | Open Access

    Mutations in nucleotide-binding oligomerization domain protein 12 (NLRP12) are known to effect inflammatory processes. Here the authors show that NLRP12-mediated proteasomal degradation of NOD2 in monocytes promotes bacterial tolerance and colonisation in a model of enteric infection.

    • Sylvain Normand
    • , Nadine Waldschmitt
    •  & Mathias Chamaillard

  • Article
    | Open Access

    Human leukocyte antigens (HLA) are multi-allelic and polymorphic genes that present antigens to immune cells for inducing protective immunity. Here, using systems biology and structural approaches, the authors show that micropolymorphism of three HLA has effects beyond the modulation of antigen diversity.

    • Patricia T. Illing
    • , Phillip Pymm
    •  & Anthony W. Purcell

  • Article
    | Open Access

    Mutations in genes encoding NAPDH oxidase subunits are known to be causative for the primary immunodeficiency chronic granulomatous disease (CGD). Here, the authors identify CYBC1 mutations in patients with CGD and show that CYBC1 is important for formation of the NADPH complex and respiratory burst.

    • Gudny A. Arnadottir
    • , Gudmundur L. Norddahl
    •  & Kari Stefansson

  • Article
    | Open Access

    Knowledge on how antibody responses have evolved is critical for the induction of protective immunity. Here the authors analyse, using high-throughput sequencing of both exon and intron regions, the mutation and lineage development of an HIV-neutralizing antibody to find an unexpected early emergence of broadly neutralizing species.

    • Erik L. Johnson
    • , Nicole A. Doria-Rose
    •  & George Georgiou

  • Article
    | Open Access

    Genetic risk loci for tuberculosis (TB) have so far been identified in African and Russian populations. Here, the authors perform a three-stage GWAS for TB in Han Chinese populations and find two risk loci near ESRRB and TGM6 and further demonstrate that tgm6 protects mice from Mtb infection.

    • Ruijuan Zheng
    • , Zhiqiang Li
    •  & Baoxue Ge

  • Article
    | Open Access

    Most of the more than 200 known genetic risk loci for inflammatory bowel disease (IBD) reside in regulatory regions. Here, the authors provide eQTL datasets for six circulating immune cell types and ileal, colonic and rectal biopsies to map regulatory modules and identify potential causative genes for IBD.

    • Yukihide Momozawa
    • , Julia Dmitrieva
    •  & Michel Georges

  • Article
    | Open Access

    The AID/APOBEC cytidine deaminase family are nucleic acid editors, important for antigen receptor expression and thought to have evolved along with vertebrate adaptive immunity. Here the authors show this family may have evolved prior to adaptive immunity as members with cytidine deaminase activity are present and functional in invertebrate sea urchins and brachiopods.

    • Mei-Chen Liu
    • , Wen-Yun Liao
    •  & Sebastian D. Fugmann

  • Article
    | Open Access

    DNA methylation is known to contribute to B cell differentiation, but de novo methylation has not been studied in this context. Here the authors use a conditional Dnmt3a/b knockout mouse to map the function of de novo DNA methylation in B cell differentiation and the development of humoral immunity.

    • Benjamin G. Barwick
    • , Christopher D. Scharer
    •  & Jeremy M. Boss

  • Article
    | Open Access

    Leprosy, caused by infection with Mycobacterium leprae, was common in Europe in the Middle Ages. Here, Krause-Kyora et al. analyze ancient DNA from a medieval Danish leprosarium to assemble 10 complete bacterial genomes and perform association analysis of the DRB1*15:01 allele with risk of leprosy infection.

    • Ben Krause-Kyora
    • , Marcel Nutsua
    •  & Almut Nebel

  • Article
    | Open Access

    B and T cell receptor diversity can be studied by high-throughput immune receptor sequencing. Here, the authors develop a software tool, IGoR, that calculates the likelihoods of potential V(D)J recombination and somatic hypermutation scenarios from raw immune sequence reads.

    • Quentin Marcou
    • , Thierry Mora
    •  & Aleksandra M. Walczak

  • Article
    | Open Access

    Nucleic acid sensing is important to ensure that an innate immune response is only mounted against microbial nucleic acid. Here, the authors identify loss-of-function mutations in the DNASE2 gene that cause type I interferon-mediated autoinflammation due to enhanced systemic interferon signaling.

    • Mathieu P. Rodero
    • , Alessandra Tesser
    •  & Yanick J. Crow

  • Article
    | Open Access

    Mouse γδ T cells have diverse functional subsets, but how these subsets are programmed during their development is still unclear. Here the authors show that three surface markers, CD117, CD200 and CD371, refine the development of γδ T cells in the thymus into three pathways programming distinct γδ T cell subsets.

    • Terkild Brink Buus
    • , Niels Ødum
    •  & Jens Peter Holst Lauritsen

  • Article
    | Open Access

    Classical Hodgkin lymphoma is a cancer that originates in lymph nodes. Little is known about its genetic susceptibility. Here, the authors combined existing and new genome-wide association studies to identify risk loci for classical Hodgkin lymphoma at 6q22.33, and nodular sclerosis Hodgkin lymphoma at 3q28, 6q23.3, 10p14, 13q34, 16p13.13.

    • Amit Sud
    • , Hauke Thomsen
    •  & Richard S. Houlston

  • Article
    | Open Access

    T cell receptors are generated by somatic gene recombination, and are normally selected against autoreactivity. Here the authors show that CD4 T cells from patients with autoimmune type 1 diabetes have shorter TCRβ sequences, broader repertoire diversity, and more repertoire sharing than those from healthy individuals.

    • Iria Gomez-Tourino
    • , Yogesh Kamra
    •  & Mark Peakman

  • Article
    | Open Access

    Host-parasite coevolution can lead to arms races favouring novel immunogenetic alleles or the maintenance of diversity in a balanced polymorphism. Here, Lighten et al. combine data on MHC diversity across three guppy species and simulations to show that polymorphisms of immunogenetic supertypes may persist even as alleles within supertypes are involved in an arms race.

    • Jackie Lighten
    • , Alexander S. T. Papadopulos
    •  & Cock van Oosterhout

  • Article
    | Open Access

    Microglia cells in the brain regulate immune responses, but in ageing can negatively affect brain function. Here the authors show that the chronic presence of type I interferon in aged mouse brain impedes cognitive ability by altering microglia transcriptome and limiting Mef2C, a microglia ‘off’ signal.

    • Aleksandra Deczkowska
    • , Orit Matcovitch-Natan
    •  & Michal Schwartz

  • Article
    | Open Access

    IgE is an important mediator of protective immunity as well as allergic reaction, but how high affinity IgE antibodies are produced in memory responses is not clear. Here the authors show that IgE can be generated via class-switch recombination in IgG1 memory B cells without additional somatic hypermutation.

    • Jin-Shu He
    • , Sharrada Subramaniam
    •  & Maria A. Curotto de Lafaille

  • Article
    | Open Access

    Insight into the genetic influence on the immune response is important for the understanding of interindividual variability in human pathologies. Here, the authors generate transcriptome data from human blood monocytes stimulated with various immune stimuli and provide a time-resolved response eQTL map.

    • Sarah Kim-Hellmuth
    • , Matthias Bechheim
    •  & Veit Hornung

  • Article
    | Open Access

    HLA-C expression levels correlate with immune responses to pathogens and autoimmunity, and vary in an allele-specific manner across individuals. Here the authors identify factors that drive differential expression of HLA-C allomorphs at the cell surface, and influence the structure of the peptide-binding cleft and diversity of peptides bound by HLA-C molecules.

    • Gurman Kaur
    • , Stephanie Gras
    •  & Lars Fugger

  • Article
    | Open Access

    T helper 17 (Th17) cells can be pathogenic, but what controls this phenotype is unclear. Here the authors show that the transcription factor JunB promotes proinflammatory Th17 function by regulating the transcription of multiple Th17-related genes.

    • Zafrul Hasan
    • , Shin-ichi Koizumi
    •  & Hiroki Ishikawa

  • Article
    | Open Access

    B cell development involves sequential rearrangement of the immunoglobulin chains, but fine control over the selection process remains a mystery. Here the authors show that individual alleles in pre-B cells are clonally unique and result from stochastic activation of V gene segments to induce optimal generation of a diverse repertoire.

    • Rena Levin-Klein
    • , Shira Fraenkel
    •  & Yehudit Bergman

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