{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T16:24:33Z","timestamp":1792081473746,"version":"4.4.0"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T00:00:00Z","timestamp":1628726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>The gastrointestinal (GI) tract is frequently affected by inborn errors of immunity (IEI), and GI manifestations can be present in IEI patients before a diagnosis is confirmed. We aimed to investigate clinical features, endoscopic and histopathologic findings in IEI patients. This was a retrospective cohort study conducted from 1995 to 2020. Eligible patients were diagnosed with IEI and had GI manifestations that were enough to require endoscopies. IEI was classified according to the International Union of Immunological Societies classification. Of 165 patients with IEI, 55 (33.3%) had GI manifestations, and 19 (11.5%) underwent endoscopy. Among those 19 patients, nine (47.4%) initially presented with GI manifestations. Thirteen patients (68.4%) were male, and the mean age of patients 11.5 \u00b1 7.9 years (range, 0.6 \u2013 26.6) when they were consulted and evaluated with endoscopy. The most common type of IEI with severe GI symptoms was \u201cDisease of immune dysregulation\u201d (31.6%) followed by \u201cPhagocyte defects\u201d (26.3%), according to the International Union of Immunological Societies classification criteria. Patients had variable GI symptoms such as chronic diarrhea (68.4%), hematochezia (36.8%), abdominal pain (31.6%), perianal disease (10.5%), and recurrent oral ulcers (10.5%). During the follow-up period, three patients developed GI tract neoplasms (early gastric carcinoma, mucosa associated lymphoid tissue lymphoma of colon, and colonic tubular adenoma, 15.8%), and 12 patients (63.2%) were diagnosed with inflammatory bowel disease (IBD)-like colitis. Investigating immunodeficiency in patients with atypical GI symptoms can provide an opportunity for correct diagnosis and appropriate disease-specific therapy. Gastroenterologists and immunologists should consider endoscopy when atypical GI manifestations appear in IEI patients to determine if IBD-like colitis or neoplasms including premalignant and malignant lesions have developed. Also, if physicians in various fields are better educated about IEI-specific complications, early diagnosis and disease-specific treatment for IEI will be made possible.<\/jats:p>","DOI":"10.3389\/fimmu.2021.698721","type":"journal-article","created":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T05:49:50Z","timestamp":1628747390000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Needs for Increased Awareness of Gastrointestinal Manifestations in Patients With Human Inborn Errors of Immunity"],"prefix":"10.3389","volume":"12","author":[{"given":"Eun Sil","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongsub","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoonsun","family":"Yoon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiyoung","family":"Kwon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sangwoo","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihyun","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang Mo","family":"Ahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soomin","family":"Ahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yon Ho","family":"Choe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yae-Jean","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi Jin","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,8,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1007\/s10875-020-00758-x","article-title":"Human Inborn Errors of Immunity: 2019 Update of the IUIS Phenotypical Classification","volume":"40","author":"Bousfiha","year":"2020","journal-title":"J Clin Immunol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2013.02.024","article-title":"Diagnosis and Treatment of Gastrointestinal Disorders in Patients With Primary Immunodeficiency","volume":"11","author":"Agarwal","year":"2013","journal-title":"Clin Gastroenterol Hepatol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2003.023671","article-title":"Modulating the Intestinal Immune System: The Role of Lymphotoxin and GALT Organs","volume":"53","author":"Spahn","year":"2004","journal-title":"Gut"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/157948","article-title":"The Role of the Intestinal Context in the Generation of Tolerance and Inflammation","volume":"2012","author":"Reis","year":"2012","journal-title":"Clin Dev Immunol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0b013e3181efe56b","article-title":"Recognizing Gastrointestinal and Hepatic Manifestations of Primary Immunodeficiency Diseases","volume":"51","author":"Guerrerio","year":"2010","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1007\/s12016-018-8689-9","article-title":"Gastrointestinal Disorders Associated With Primary Immunodeficiency Diseases","volume":"57","author":"Hartono","year":"2019","journal-title":"Clin Rev Allergy Immunol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.iac.2018.08.006","article-title":"Gastrointestinal Manifestations and Complications of Primary Immunodeficiency Disorders","volume":"39","author":"Agarwal","year":"2019","journal-title":"Immunol Allergy Clin North Am"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.crohns.2014.04.005","article-title":"Consensus Guidelines of ECCO\/ESPGHAN on the Medical Management of Pediatric Crohn\u2019s Disease","volume":"8","author":"Ruemmele","year":"2014","journal-title":"J Crohns Colitis"},{"key":"B9","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1016\/j.cgh.2015.10.030","article-title":"Gastrointestinal Features of Chronic Granulomatous Disease Found During Endoscopy","volume":"14","author":"Khangura","year":"2016","journal-title":"Clin Gastroenterol Hepatol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.2169\/internalmedicine.56.7909","article-title":"The Effective Treatment With Cyclosporine of a Ulcerative Colitis Patient With Concurrent Idiopathic Thrombocytopenic Purpura Who Subsequently Developed Spontaneous Pneumomediastinum","volume":"56","author":"Iwasa","year":"2017","journal-title":"Intern Med"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1007\/s00384-014-1903-1","article-title":"Brooks S. A Role of Colectomy in Immune Thrombocytopenic Purpura Associated With Ulcerative Colitis: A Case Report and a Review of the Literature","volume":"29","author":"Negoro","year":"2014","journal-title":"Int J Colorectal Dis"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e318297427d","article-title":"Gastrointestinal Histopathology in Chronic Granulomatous Disease: A Study of 87 Patients","volume":"37","author":"Alimchandani","year":"2013","journal-title":"Am J Surg Pathol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1159\/000492569","article-title":"Gastrointestinal Manifestations in Children With Primary Immunodeficiencies: Single Center: 12 Years Experience","volume":"37","author":"Akkelle","year":"2019","journal-title":"Dig Dis"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3345\/cep.2019.01347","article-title":"Systematic Review of Literature and Analysis of Big Data From the National Health Insurance System on Primary Immunodeficiencies in Korea","volume":"64","author":"Son","year":"2021","journal-title":"Clin Exp Pediatr"},{"key":"B15","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/j.gtc.2019.02.004","article-title":"Primary Immunodeficiency and the Gut","volume":"48","author":"Schwimmer","year":"2019","journal-title":"Gastroenterol Clin North Am"},{"key":"B16","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.clim.2018.07.015","article-title":"Th1-Skewed Profile and Excessive Production of Proinflammatory Cytokines in a NFKB1-Deficient Patient With CVID and Severe Gastrointestinal Manifestations","volume":"195","author":"Dieli-Crimi","year":"2018","journal-title":"Clin Immunol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3349\/ymj.2020.61.6.542","article-title":"Successful Sirolimus Treatment for Korean Patients With Activated Phosphoinositide 3-Kinase Delta Syndrome 1: The First Case Series in Korea","volume":"61","author":"Kang","year":"2020","journal-title":"Yonsei Med J"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-002-1011-z","article-title":"Association of Glycogen Storage Disease 1b and Crohn Disease: Results of a North American Survey","volume":"161","author":"Dieckgraefe","year":"2002","journal-title":"Eur J Pediatr"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1111\/pai.12734","article-title":"Inflammatory Bowel Disease Caused by Primary Immunodeficiencies-Clinical Presentations, Review of Literature, and Proposal of a Rational Diagnostic Algorithm","volume":"28","author":"Tegtmeyer","year":"2017","journal-title":"Pediatr Allergy Immunol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-018-0524-9","article-title":"The Treatment of Inflammatory Bowel Disease in Patients With Selected Primary Immunodeficiencies","volume":"38","author":"Shouval","year":"2018","journal-title":"J Clin Immunol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/key058","article-title":"The Multifaceted Presentation of Chronic Recurrent Multifocal Osteomyelitis: A Series of 486 Cases From the Eurofever International Registry","author":"Girschick","year":"2018","journal-title":"Rheumatol (Oxford)"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2009.05.005","article-title":"NOD2-Associated Diseases: Bridging Innate Immunity and Autoinflammation","volume":"134","author":"Borzutzky","year":"2010","journal-title":"Clin Immunol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2010-3680","article-title":"Clinical Features That Identify Children With Primary Immunodeficiency Diseases","volume":"127","author":"Subbarayan","year":"2011","journal-title":"Pediatrics"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1177\/0884533614555234","article-title":"Growth Failure and Nutrition Considerations in Chronic Childhood Wasting Diseases","volume":"30","author":"Kyle","year":"2015","journal-title":"Nutr Clin Pract"},{"key":"B25","article-title":"A Study of Malnutrition in Iranian Patients With Primary Antibody Deficiency","volume":"3","author":"Kouhkan","year":"2004","journal-title":"Iran J Allergy Asthma Immunol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.jped.2018.11.006","article-title":"Repercussions of Inborn Errors of Immunity on Growth","volume":"95","author":"Goudouris","year":"2019","journal-title":"J Pediatr (Rio J)"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.5152\/tpa.2014.1810","article-title":"Profile of the Patients Who Present to Immunology Outpatient Clinics Because of Frequent Infections","volume":"49","author":"Ald\u0131rmaz","year":"2014","journal-title":"Turk Pediatri Ars"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-008-9260-x","article-title":"Primary Immunodeficiency Diseases in Egyptian Children: A Single-Center Study","volume":"29","author":"Reda","year":"2009","journal-title":"J Clin Immunol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"e28091","DOI":"10.1002\/pbc.28091","article-title":"Malignancy and Lymphoid Proliferation in Primary Immune Deficiencies; Hard to Define, Hard to Treat","volume":"67","author":"Kiykim","year":"2020","journal-title":"Pediatr Blood Cancer"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-014-0124-2","article-title":"IgA Deficiency and Risk of Cancer: A Population-Based Matched Cohort Study","volume":"35","author":"Ludvigsson","year":"2015","journal-title":"J Clin Immunol"},{"key":"B31","article-title":"Development of Cancer in Patients With Primary Immunodeficiencies","volume":"28","author":"Salavoura","year":"2008","journal-title":"Anticancer Res"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.2174\/1573396315666190917154058","article-title":"Primary Immunodeficiency and Cancer in Children; A Review of the Literature","volume":"15","author":"Kebudi","year":"2019","journal-title":"Curr Pediatr Rev"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2017.05.024","article-title":"Cancer in Primary Immunodeficiency Diseases: Cancer Incidence in the United States Immune Deficiency Network Registry","volume":"141","author":"Mayor","year":"2018","journal-title":"J Allergy Clin Immunol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.11406\/rinketsu.59.2459","article-title":"Primary Immunodeficiencies and Hematological Malignancies","volume":"59","author":"Kanegane","year":"2018","journal-title":"Rinsho Ketsueki"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1080\/10428194.2019.1672056","article-title":"Primary Immunodeficiencies and Lymphoma: A Systematic Review of Literature","volume":"61","author":"Herber","year":"2020","journal-title":"Leuk Lymphoma"},{"key":"B36","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1038\/nrrheum.2017.198","article-title":"Autoimmunity and Primary Immunodeficiency: Two Sides of the Same Coin","volume":"14","author":"Schmidt","year":"2017","journal-title":"Nat Rev Rheumatol"},{"key":"B37","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.jaut.2019.01.011","article-title":"Primary Immunodeficiency and Autoimmunity: A Comprehensive Review","volume":"99","author":"Amaya-Uribe","year":"2019","journal-title":"J\u00a0Autoimmun"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1007\/s12026-015-8733-2","article-title":"Subclinical Intestinal Inflammation in Chronic Granulomatous Disease Patients","volume":"64","author":"Broides","year":"2015","journal-title":"Immunol Res"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.5223\/pghn.2019.22.1.41","article-title":"Recent Advance in Very Early Onset Inflammatory Bowel Disease","volume":"22","author":"Shim","year":"2019","journal-title":"Pediatr Gastroenterol Hepatol Nutr"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1542\/pir.26-9-314","article-title":"Inflammatory Bowel Disease","volume":"26","author":"Hyams","year":"2005","journal-title":"Pediatr Rev"},{"key":"B41","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.jaci.2019.11.003","article-title":"The Microbiome and Inflammatory Bowel Disease","volume":"145","author":"Glassner","year":"2020","journal-title":"J Allergy Clin Immunol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.698721\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T05:49:54Z","timestamp":1628747394000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.698721\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,12]]},"references-count":41,"alternative-id":["10.3389\/fimmu.2021.698721"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2021.698721","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,12]]},"article-number":"698721"}}