{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T21:17:51Z","timestamp":1790630271623,"version":"4.1.0"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,6,7]],"date-time":"2023-06-07T00:00:00Z","timestamp":1686096000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["17411962500, 2018BR05"],"award-info":[{"award-number":["17411962500, 2018BR05"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012303","name":"Key Disciplines Construction Project of Shanghai Municipal","doi-asserted-by":"publisher","award":["shslczdzk01302"],"award-info":[{"award-number":["shslczdzk01302"]}],"id":[{"id":"10.13039\/501100012303","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Inborn errors of immunity (IEI) are a heterogeneous group of disorders characterized by increased risk of infections, autoimmunity, autoinflammatory diseases, malignancy and allergy. Next-generation sequencing has revolutionized the identification of genetic background of these patients and assists in diagnosis and treatment. In this study, we identified a probable unique monogenic cause of IEI, and evaluated the immunological methods and pathogenic detections.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A family with a member with a clinical diagnosis of IEI was screened by whole genomic sequencing (WGS). Demographic data, clinical manifestations, medical history, physical examination, laboratory findings and imaging features of the patient were extracted from medical records. Comprehensive immune monitoring methods include a complete blood count with differential, serum levels of cytokines and autoantibodies, T-cell and B-cell subsets analysis and measurement of serum immunoglobulins. In addition, metagenomic sequencing (mNGS) of blood, cerebrospinal fluid and biopsy from small intestine were used to detect potential pathogens.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The patient manifested with recurrent infections and autoimmune disorders, who was eventually diagnosed with IEI. Repetitive mNGS tests of blood, cerebrospinal fluid and biopsy from small intestine didn\u2019t detect pathogenic microorganism. Immunological tests showed a slightly decreased level of IgG than normal, elevated levels of tumor necrosis factor and interleukin-6. Lymphocyte flow cytometry showed elevated total B cells and natural killer cells, decreased total T cells and B-cell plasmablasts. WGS of the patient identified a novel heterozygous mutation in <jats:italic>IRF2BP2<\/jats:italic> (c.439_450dup p. Thr147_Pro150dup), which was also confirmed in his father. The mutation was classified as variant of uncertain significance (VUS) according to the American College of Medical Genetics and Genomics guidelines.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We identified a novel <jats:italic>IRF2BP2<\/jats:italic> mutation in a family with a member diagnosed with IEI. Immune monitoring and WGS as auxiliary tests are helpful in identifying genetic defects and assisting diagnosis in patients with clinically highly suspected immune abnormalities and deficiencies in inflammation regulation. In addition, mNGS techniques allow a more comprehensive assessment of the pathogenic characteristics of these patients. This report further validates the association of IRF2BP2 deficiency and IEI, and expands IEI phenotypes.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.967345","type":"journal-article","created":{"date-parts":[[2023,6,7]],"date-time":"2023-06-07T06:25:41Z","timestamp":1686119141000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Case Report: A novel IRF2BP2 mutation in an IEI patient with recurrent infections and autoimmune disorders"],"prefix":"10.3389","volume":"14","author":[{"given":"Yiwen","family":"Pan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoguo","family":"Shang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuwen","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianying","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Ji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,6,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2019.02.004","article-title":"The European society for immunodeficiencies (ESID) registry working definitions for the clinical diagnosis of inborn errors of immunity","volume":"7","author":"Seidel","year":"2019","journal-title":"J Allergy Clin Immunol Pract"},{"key":"B2","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1186\/s13223-018-0290-5","article-title":"Primary immunodeficiency","volume":"14","author":"McCusker","year":"2018","journal-title":"Allergy Asthma. Clin Immunol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1007\/s10875-007-9103-1","article-title":"Population prevalence of diagnosed primary immunodeficiency diseases in the united states","volume":"27","author":"Boyle","year":"2007","journal-title":"J Clin Immunol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s10875-012-9751-7","article-title":"Primary immunodeficiency diseases worldwide: more common than generally thought","volume":"33","author":"Bousfiha","year":"2013","journal-title":"J Clin Immunol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-022-01352-z","article-title":"The 2022 update of IUIS phenotypical classification for human inborn errors of immunity","volume":"42","author":"Bousfiha","year":"2022","journal-title":"J Clin Immunol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-022-01289-3","article-title":"Human inborn errors of immunity: 2022 update on the classification from the international union of immunological societies expert committee","volume":"42","author":"Tangye","year":"2022","journal-title":"J Clin Immunol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1097\/ACI.0000000000000689","article-title":"Primary immune regulatory disorders: a growing universe of immune dysregulation","volume":"20","author":"Chan","year":"2020","journal-title":"Curr Opin Allergy Clin Immunol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-015-0149-1","article-title":"The duesseldorf warning signs for primary immunodeficiency: is it time to change the rules","volume":"35","author":"Lankisch","year":"2015","journal-title":"J Clin Immunol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2021.04.015","article-title":"Initial presenting manifestations in 16,486 patients with inborn errors of immunity include infections and noninfectious manifestations","volume":"148","author":"Thalhammer","year":"2021","journal-title":"J Allergy Clin Immunol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.753978","article-title":"Monogenic adult-onset inborn errors of immunity","volume":"12","author":"Staels","year":"2021","journal-title":"Front Immunol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2015-103690","article-title":"Genes associated with common variable immunodeficiency: one diagnosis to rule them all","volume":"53","author":"Bogaert","year":"2016","journal-title":"J Med Genet"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1002\/JLB.MR1218-507R","article-title":"IRF2BP2: a new player in the regulation of cell homeostasis","volume":"106","author":"Ramalho-Oliveira","year":"2019","journal-title":"J Leukoc. Biol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathmechdis-012418-012751","article-title":"Clinical metagenomic next-generation sequencing for pathogen detection","volume":"14","author":"Gu","year":"2019","journal-title":"Annu Rev Pathol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2020.05.008","article-title":"Executive summary of the consensus document on the diagnosis and management of patients with primary immunodeficiencies","volume":"8","author":"Cordero","year":"2020","journal-title":"J Allergy Clin Immunol Pract"},{"key":"B15","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.molimm.2021.06.018","article-title":"Approach to genetic diagnosis of inborn errors of immunity through next-generation sequencing","volume":"137","author":"Karimi","year":"2021","journal-title":"Mol Immunol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2021.02.011","article-title":"Next-generation sequencing for inborn errors of immunity","volume":"82","author":"Lee","year":"2021","journal-title":"Hum Immunol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.jped.2020.11.007","article-title":"Inborn errors of immunity: how to diagnose them","volume":"97","author":"Grumach","year":"2021","journal-title":"J Pediatr"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.721289","article-title":"A critical review on the standardization and quality assessment of nonfunctional laboratory tests frequently used to identify inborn errors of immunity","volume":"12","author":"Perazzio","year":"2021","journal-title":"Front Immunol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1007\/s10875-016-0260-y","article-title":"Next generation sequencing data analysis in primary immunodeficiency disorders-future directions","volume":"36","author":"Fang","year":"2016","journal-title":"J Clin Immunol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2016.190","article-title":"Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American college of medical genetics and genomics","volume":"19","author":"Kalia","year":"2017","journal-title":"Genet Med"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-021-01171-4","article-title":"Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2021 update: a policy statement of the American college of medical genetics and genomics (ACMG)","volume":"23","author":"Miller","year":"2021","journal-title":"Genet Med"},{"key":"B22","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1016\/S1474-4422(15)00401-9","article-title":"A clinical approach to diagnosis of autoimmune encephalitis.Lancet","volume":"15","author":"Graus","year":"2016","journal-title":"Neurol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01317","article-title":"Autologous stem cell transplantation in common variable immunodeficiency: a case of successful treatment of severe refractory autoimmune encephalitis","volume":"11","author":"Froehlich","year":"2020","journal-title":"Front Immunol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01119","article-title":"Frequency and manifestations of autoimmunity among children registered in the Kuwait national primary immunodeficiency registry","volume":"11","author":"Massaad","year":"2020","journal-title":"Front Immunol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1111\/apt.14794","article-title":"Long-term efficacy and safety of ustekinumab for crohn\u2019s disease through the second year of therapy","volume":"48","author":"Sandborn","year":"2018","journal-title":"Aliment. Pharmacol Ther"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.13469","article-title":"Long-term efficacy and safety of ustekinumab, with and without dosing adjustment, in patients with moderate-to-severe psoriasis: results from the PHOENIX 2 study through 5 years of follow-up","volume":"172","author":"Langley","year":"2015","journal-title":"Br J Dermatol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1900750","article-title":"Ustekinumab as induction and maintenance therapy for ulcerative colitis","volume":"381","author":"Sands","year":"2019","journal-title":"N Engl J Med"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00974-10","article-title":"Interferon regulatory factor 2 binding protein 2 is a new NFAT1 partner and represses its transcriptional activity","volume":"31","author":"Carneiro","year":"2011","journal-title":"Mol Cell Biol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.2A0815-368R","article-title":"IRF2BP2 transcriptional repressor restrains naive CD4 T cell activation and clonal expansion induced by TCR triggering","volume":"100","author":"Secca","year":"2016","journal-title":"J Leukoc. Biol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1512234","article-title":"Loss of b cells in patients with heterozygous mutations in IKAROS","volume":"374","author":"Kuehn","year":"2016","journal-title":"N Engl J Med"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.655307","article-title":"The transcriptional Co-factor IRF2BP2: a new player in tumor development and microenvironment","volume":"9","author":"Pastor","year":"2021","journal-title":"Front Cell Dev Biol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2016.01.018","article-title":"Mutation in IRF2BP2 is responsible for a familial form of common variable immunodeficiency disorder","volume":"138","author":"Keller","year":"2016","journal-title":"J Allergy Clin Immunol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2021.04.005","article-title":"Molecular diagnosis of childhood immune dysregulation, polyendocrinopathy, and enteropathy, and implications for clinical management","volume":"149","author":"Baxter","year":"2022","journal-title":"J Allergy Clin Immunol"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/rheumatology\/keac575","article-title":"Novel mutation and expanding phenotype in IRF2BP2 deficiency","volume":"10","author":"Ko\u00a8rholz","year":"2022","journal-title":"Rheumatol (Oxford)."},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-013-1331-2","article-title":"Where genotype is not predictive of phenotype: towards an understanding of the molecular basis of reduced penetrance in human inherited disease","volume":"132","author":"Cooper","year":"2013","journal-title":"Hum Genet"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.938240","article-title":"Multi-omics analysis of na\u00efve b cells of patients harboring the C104R mutation in TACI","volume":"16","author":"Ramirez","year":"2022","journal-title":"Front Immunol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20140520","article-title":"Guidelines for genetic studies in single patients: lessons from primary immunodeficiencies","volume":"211","author":"Casanova","year":"2014","journal-title":"J Exp Med"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.967345\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,7]],"date-time":"2023-06-07T06:25:45Z","timestamp":1686119145000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.967345\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,7]]},"references-count":37,"alternative-id":["10.3389\/fimmu.2023.967345"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2023.967345","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,7]]},"article-number":"967345"}}