{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T16:11:29Z","timestamp":1787760689611,"version":"build-2784847793"},"reference-count":106,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,3,17]],"date-time":"2024-03-17T00:00:00Z","timestamp":1710633600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Primary immune regulatory disorders (PIRDs) constitute a spectrum of inborn errors of immunity (IEIs) that are primarily characterized by autoimmunity, lymphoproliferation, atopy, and malignancy. In PIRDs, infections are infrequent compared to other IEIs. While susceptibility to infection primarily stems from antibody deficiency, it is sometimes associated with additional innate immune and T or NK cell defects. The use of immunotherapy and chemotherapy further complicates the immune landscape, increasing the risk of diverse infections. Recurrent sinopulmonary infections, particularly bacterial infections such as those associated with staphylococcal and streptococcal organisms, are the most reported infectious manifestations. Predisposition to viral infections, especially Epstein\u2013Barr virus (EBV)-inducing lymphoproliferation and malignancy, is also seen. Notably, mycobacterial and invasive fungal infections are rarely documented in these disorders. Knowledge about the spectrum of infections in these disorders would prevent diagnostic delays and prevent organ damage. This review delves into the infection profile specific to autoimmune lymphoproliferative syndrome (ALPS), Tregopathies, and syndromes with autoimmunity within the broader context of PIRD. Despite the critical importance of understanding the infectious aspects of these disorders, there remains a scarcity of comprehensive reports on this subject.<\/jats:p>","DOI":"10.3390\/pathogens13030259","type":"journal-article","created":{"date-parts":[[2024,3,18]],"date-time":"2024-03-18T05:14:07Z","timestamp":1710738847000},"page":"259","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Infections in Disorders of Immune Regulation"],"prefix":"10.3390","volume":"13","author":[{"given":"Abarna","family":"Thangaraj","sequence":"first","affiliation":[{"name":"Pediatric Allergy Immunology Unit, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reva","family":"Tyagi","sequence":"additional","affiliation":[{"name":"Pediatric Allergy Immunology Unit, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5009-8761","authenticated-orcid":false,"given":"Deepti","family":"Suri","sequence":"additional","affiliation":[{"name":"Pediatric Allergy Immunology Unit, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7422-1453","authenticated-orcid":false,"given":"Sudhir","family":"Gupta","sequence":"additional","affiliation":[{"name":"Division of Basic and Clinical Immunology, Department of Medicine, University of California, Irvine, CA 92697, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1473","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":"ref_2","doi-asserted-by":"crossref","first-page":"1508","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":"ref_3","doi-asserted-by":"crossref","first-page":"1763","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":"ref_4","doi-asserted-by":"crossref","first-page":"1332","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":"ref_5","doi-asserted-by":"crossref","first-page":"1279201","DOI":"10.3389\/fimmu.2023.1279201","article-title":"Too much of a good thing: A review of primary immune regulatory disorders","volume":"14","author":"Tsilifis","year":"2023","journal-title":"Front. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"353","DOI":"10.3389\/fped.2019.00353","article-title":"Inborn Errors of Immunity with Immune Dysregulation: From Bench to Bedside","volume":"7","author":"Delmonte","year":"2019","journal-title":"Front. Pediatr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1182\/blood-2014-02-553834","article-title":"Defective anti-polysaccharide response and splenic marginal zone disorganization in ALPS patients","volume":"124","author":"Neven","year":"2014","journal-title":"Blood"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4798","DOI":"10.1182\/blood-2011-04-347641","article-title":"A survey of 90 patients with autoimmune lymphoproliferative syndrome related to TNFRSF6 mutation","volume":"118","author":"Neven","year":"2011","journal-title":"Blood"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1989","DOI":"10.1182\/blood-2013-10-535393","article-title":"Natural history of autoimmune lymphoproliferative syndrome associated with FAS gene mutations","volume":"123","author":"Price","year":"2014","journal-title":"Blood"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1016\/j.ajhg.2010.10.028","article-title":"Whole-Exome-Sequencing-Based Discovery of Human FADD Deficiency","volume":"87","author":"Bolze","year":"2010","journal-title":"Am. J. Hum. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e11","DOI":"10.1111\/bjh.18871","article-title":"Expanding the clinical phenotype of FADD deficiency with a novel mutation and its role in Fas-mediated apoptotic pathway","volume":"202","author":"Setia","year":"2023","journal-title":"Br. J. Haematol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1007\/s10875-020-00779-6","article-title":"Novel Compound Heterozygote Variations in FADD Identified to Cause FAS-Associated Protein with Death Domain Deficiency","volume":"40","author":"Kohn","year":"2020","journal-title":"J. Clin. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"101305","DOI":"10.1016\/j.ajoc.2022.101305","article-title":"Ocular findings associated with FADD deficiency resemble familial exudative vitreoretinopathy","volume":"25","author":"Meer","year":"2022","journal-title":"Am. J. Ophthalmol. Case Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.iac.2008.01.002","article-title":"Genetic Defects of Apoptosis and Primary Immunodeficiency","volume":"28","author":"Su","year":"2008","journal-title":"Immunol. Allergy Clin. N. Am."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"15. Bazgir, N., Tahvildari, A., Chavoshzade, Z., Jamee, M., Golchehre, Z., Karimi, A., Dara, N., Fallahi, M., Keramatipour, M., and Karamzade, A. (2023). A rare immunological disease, caspase 8 deficiency: Case report and literature review. Allergy Asthma Clin. Immunol. Off. J. Can. Soc. Allergy Clin. Immunol., 19, 29.","DOI":"10.1186\/s13223-023-00778-3"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1007\/s10875-015-0150-8","article-title":"Caspase-8 deficiency presenting as late-onset multi-organ lymphocytic infiltration with granulomas in two adult siblings","volume":"35","author":"Niemela","year":"2015","journal-title":"J. Clin. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1038\/s41586-019-1770-6","article-title":"Caspase-8 is the molecular switch for apoptosis, necroptosis and pyroptosis","volume":"575","author":"Fritsch","year":"2019","journal-title":"Nature"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"30","DOI":"10.25259\/WJWCH_29_2022","article-title":"Caspase-8 deficiency-a rare cause of immune dysregulation\u2014First case report from India","volume":"2","author":"Chougule","year":"2023","journal-title":"Wadia J. Women Child. Health"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1038\/nature01063","article-title":"Pleiotropic defects in lymphocyte activation caused by caspase-8 mutations lead to human immunodeficiency","volume":"419","author":"Chun","year":"2002","journal-title":"Nature"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1053\/j.gastro.2018.09.041","article-title":"Intestinal Inflammation and Dysregulated Immunity in Patients with Inherited Caspase-8 Deficiency","volume":"156","author":"Lehle","year":"2019","journal-title":"Gastroenterology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1038\/ni.3327","article-title":"Tolerance is established in polyclonal CD4+ T cells by distinct mechanisms, according to self-peptide expression patterns","volume":"17","author":"Malhotra","year":"2016","journal-title":"Nat. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e456","DOI":"10.1038\/emm.2017.313","article-title":"Transcriptional regulation and development of regulatory T cells","volume":"50","author":"Lee","year":"2018","journal-title":"Exp. Mol. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1016\/j.immuni.2015.10.011","article-title":"CD4+ T Cell Tolerance to Tissue-Restricted Self Antigens Is Mediated by Antigen-Specific Regulatory T Cells Rather Than Deletion","volume":"43","author":"Legoux","year":"2015","journal-title":"Immunity"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.immuni.2007.11.021","article-title":"A two-step process for thymic regulatory T cell development","volume":"28","author":"Lio","year":"2008","journal-title":"Immunity"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1016\/j.jaci.2017.10.041","article-title":"Long-term follow-up of IPEX syndrome patients after different therapeutic strategies: An international multicenter retrospective study","volume":"141","author":"Barzaghi","year":"2018","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"972746","DOI":"10.3389\/fimmu.2022.972746","article-title":"Clinical and immunological characteristics of five patients with immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome in China\u2013expanding the atypical phenotypes","volume":"13","author":"Huang","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1016\/j.jaci.2019.11.043","article-title":"Treatment with rapamycin can restore regulatory T-cell function in IPEX patients","volume":"145","author":"Passerini","year":"2020","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1016\/j.jaci.2008.09.027","article-title":"Clinical and molecular profile of a new series of patients with immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome: Inconsistent correlation between forkhead box protein 3 expression and disease severity","volume":"122","author":"Gambineri","year":"2008","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1038\/ni.3753","article-title":"BACH2 immunodeficiency illustrates an association between super-enhancers and haploinsufficiency","volume":"18","author":"Afzali","year":"2017","journal-title":"Nat. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.clim.2013.01.004","article-title":"Human IL2RA null mutation mediates immunodeficiency with lymphoproliferation and autoimmunity","volume":"146","author":"Goudy","year":"2013","journal-title":"Clin. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/s00251-022-01278-1","article-title":"Whole exome sequencing identified a novel splice donor site variant in interleukin 2 receptor alpha chain","volume":"75","author":"Waheed","year":"2023","journal-title":"Immunogenetics"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1016\/j.jaip.2019.09.027","article-title":"Effective and safe treatment of a novel IL2RA deficiency with rapamycin","volume":"8","author":"Lai","year":"2020","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.clim.2019.02.003","article-title":"CD25 deficiency: A new conformational mutation prevents the receptor expression on cell surface","volume":"201","author":"Vignoli","year":"2019","journal-title":"Clin. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1084\/jem.20182304","article-title":"Human interleukin-2 receptor \u03b2 mutations associated with defects in immunity and peripheral tolerance","volume":"216","author":"Zhang","year":"2019","journal-title":"J. Exp. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1084\/jem.20182015","article-title":"A novel human IL2RB mutation results in T and NK cell\u2013driven immune dysregulation","volume":"216","author":"Fernandez","year":"2019","journal-title":"J. Exp. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1111\/cei.13600","article-title":"Comprehensive comparison between 222 CTLA-4 haploinsufficiency and 212 LRBA deficiency patients: A systematic review","volume":"205","author":"Jamee","year":"2021","journal-title":"Clin. Exp. Immunol."},{"key":"ref_37","first-page":"339675","article-title":"Evaluating the Genetics of Common Variable Immunodeficiency: Monogenetic Model and Beyond","volume":"9","author":"Piquer","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.1016\/j.jaci.2018.10.026","article-title":"Tregopathies: Monogenic diseases resulting in regulatory T-cell deficiency","volume":"142","author":"Cepika","year":"2018","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"662645","DOI":"10.3389\/fped.2021.662645","article-title":"Different Apples, Same Tree: Visualizing Current Biological and Clinical Insights into CTLA-4 Insufficiency and LRBA and DEF6 Deficiencies","volume":"9","author":"Seidel","year":"2021","journal-title":"Front. Pediatr."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2790","DOI":"10.1016\/j.jaip.2019.06.011","article-title":"Abatacept as a Long-Term Targeted Therapy for LRBA Deficiency","volume":"7","author":"Kiykim","year":"2019","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"176","DOI":"10.25100\/cm.v50i3.3969","article-title":"Clinical, immunological and genetic characteristic of patients with clinical phenotype associated to LRBA-deficiency in Colombia","volume":"50","author":"Arango","year":"2019","journal-title":"Colomb. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1182\/blood-2018-11-887141","article-title":"Pediatric Evans syndrome is associated with a high frequency of potentially damaging variants in immune genes","volume":"134","author":"Hadjadj","year":"2019","journal-title":"Blood"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1932","DOI":"10.1016\/j.jaci.2018.02.055","article-title":"Phenotype, penetrance, and treatment of 133 CTLA-4-insufficient subjects","volume":"142","author":"Schwab","year":"2018","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"409164","DOI":"10.3389\/fimmu.2018.02012","article-title":"Increased Risk for Malignancies in 131 Affected CTLA4 Mutation Carriers","volume":"9","author":"Egg","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1016\/j.jaci.2021.04.039","article-title":"Therapeutic options for CTLA-4 insufficiency","volume":"149","author":"Egg","year":"2022","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/j.jaci.2016.01.045","article-title":"Hematopoietic stem cell transplantation for CTLA4 deficiency","volume":"138","author":"Slatter","year":"2016","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1452","DOI":"10.1016\/j.jaci.2019.12.896","article-title":"Long-term outcome of LRBA deficiency in 76 patients after various treatment modalities as evaluated by the immune deficiency and dysregulation activity (IDDA) score","volume":"145","author":"Tesch","year":"2020","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1016\/j.ajhg.2012.04.015","article-title":"Deleterious Mutations in LRBA Are Associated with a Syndrome of Immune Deficiency and Autoimmunity","volume":"90","author":"Tampella","year":"2012","journal-title":"Am. J. Hum. Genet."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1007\/s10875-020-00799-2","article-title":"Clinical Phenotypes and Immunological Characteristics of 18 Egyptian LRBA Deficiency Patients","volume":"40","author":"Meshaal","year":"2020","journal-title":"J. Clin. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/s10875-015-0224-7","article-title":"Spectrum of Phenotypes Associated with Mutations in LRBA","volume":"36","author":"Alkhairy","year":"2016","journal-title":"J. Clin. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1007\/s10875-019-00677-6","article-title":"A Spectrum of Clinical Findings from ALPS to CVID: Several Novel LRBA Defects","volume":"39","author":"Cagdas","year":"2019","journal-title":"J. Clin. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1007\/s10875-017-0446-y","article-title":"Multiple Presentations of LRBA Deficiency: A Single-Center Experience","volume":"37","author":"Haskologlu","year":"2017","journal-title":"J. Clin. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1016\/j.jaci.2020.05.052","article-title":"DEF6 deficiency, a mendelian susceptibility to EBV infection, lymphoma, and autoimmunity","volume":"147","author":"Fournier","year":"2021","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3106","DOI":"10.1038\/s41467-019-10812-x","article-title":"Human DEF6 deficiency underlies an immunodeficiency syndrome with systemic autoimmunity and aberrant CTLA-4 homeostasis","volume":"10","author":"Serwas","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"770077","DOI":"10.3389\/fped.2022.770077","article-title":"STAT3 gain-of-function syndrome","volume":"10","author":"Vogel","year":"2023","journal-title":"Front. Pediatr."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1182\/blood-2014-11-610592","article-title":"STAT3: Too much may be worse than not enough!","volume":"125","author":"Haddad","year":"2015","journal-title":"Blood"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1958","DOI":"10.1016\/j.jaip.2019.02.018","article-title":"Clinical Aspects of STAT3 Gain-of-Function Germline Mutations: A Systematic Review","volume":"7","author":"Fabre","year":"2019","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1016\/j.jaci.2022.09.002","article-title":"Monogenic early-onset lymphoproliferation and autoimmunity: Natural history of STAT3 gain-of-function syndrome","volume":"151","author":"Leiding","year":"2023","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1182\/blood-2014-09-602763","article-title":"Early-onset lymphoproliferation and autoimmunity caused by germline STAT3 gain-of-function mutations","volume":"125","author":"Milner","year":"2015","journal-title":"Blood"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.clim.2017.05.021","article-title":"STAT3 gain-of-function mutations associated with autoimmune lymphoproliferative syndrome like disease deregulate lymphocyte apoptosis and can be targeted by BH3 mimetic compounds","volume":"181","author":"Nabhani","year":"2017","journal-title":"Clin. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1111\/cei.13625","article-title":"Novel STAT-3 gain-of-function variant with hypogammaglobulinemia and recurrent infection phenotype","volume":"205","author":"Tsumura","year":"2021","journal-title":"Clin. Exp. Immunol."},{"key":"ref_62","first-page":"101125","article-title":"STAT3 gain-of-function mutation in a patient with pulmonary Mycobacterium abscessus infection","volume":"30","author":"Johnson","year":"2020","journal-title":"Respir. Med. Case Rep."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.mce.2018.01.016","article-title":"Partial growth hormone insensitivity and dysregulatory immune disease associated with de novo germline activating STAT3 mutations","volume":"473","author":"Scaglia","year":"2018","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1007\/s10875-021-01011-9","article-title":"Ledipasvir\/Sofosbuvir Eradicates Hepatitis C in an Immunodeficient STAT3-GOF Patient","volume":"41","author":"Thalhammer","year":"2021","journal-title":"J. Clin. Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1186\/s13223-020-00462-w","article-title":"The clinical, immunological and genetic features of 12 Chinese patients with STAT3 mutations","volume":"16","author":"Lin","year":"2020","journal-title":"Allergy Asthma Clin. Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1007\/s10875-021-00975-y","article-title":"Clinical and Immunological Heterogeneity in Japanese Patients with Gain-of-Function Variants in STAT3","volume":"41","author":"Tanita","year":"2021","journal-title":"J. Clin. Immunol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1032","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":"ref_68","doi-asserted-by":"crossref","first-page":"568","DOI":"10.3389\/fimmu.2019.00568","article-title":"Assessing the Functional Relevance of Variants in the IKAROS Family Zinc Finger Protein 1 (IKZF1) in a Cohort of Patients with Primary Immunodeficiency","volume":"10","author":"Eskandarian","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1007\/s10875-019-00643-2","article-title":"IKZF1 Loss-of-Function Variant Causes Autoimmunity and Severe Familial Antiphospholipid Syndrome","volume":"39","author":"Guffroy","year":"2019","journal-title":"J. Clin. Immunol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"3071","DOI":"10.1172\/JCI98164","article-title":"Dominant-negative IKZF1 mutations cause a T, B, and myeloid cell combined immunodeficiency","volume":"128","author":"Boutboul","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.jaci.2019.03.025","article-title":"Allogeneic hematopoietic stem cell transplant outcomes for patients with dominant negative IKZF1\/IKAROS mutations","volume":"144","author":"Kellner","year":"2019","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"eabi7160","DOI":"10.1126\/sciimmunol.abi7160","article-title":"Gain-of-function IKZF1 variants in humans cause immune dysregulation associated with abnormal T\/B cell late differentiation","volume":"7","author":"Hoshino","year":"2022","journal-title":"Sci. Immunol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10875-020-00936-x","article-title":"IKAROS-Associated Diseases in 2020: Genotypes, Phenotypes, and Outcomes in Primary Immune Deficiency\/Inborn Errors of Immunity","volume":"41","author":"Kuehn","year":"2021","journal-title":"J. Clin. Immunol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1111\/pde.14076","article-title":"A novel pathogenic FERMT1 variant in four families with Kindler syndrome in Argentina","volume":"37","author":"Valinotto","year":"2020","journal-title":"Pediatr. Dermatol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1111\/scd.12165","article-title":"Oral manifestations in Kindler syndrome: Case report and discussion of literature findings","volume":"36","author":"Barbosa","year":"2016","journal-title":"Spec. Care Dentist."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"e88782","DOI":"10.1172\/jci.insight.88782","article-title":"Redefined clinical features and diagnostic criteria in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy","volume":"1","author":"Ferre","year":"2016","journal-title":"JCI Insight."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"3546","DOI":"10.1210\/jc.2017-00139","article-title":"Expanding the Phenotypic and Genotypic Landscape of Autoimmune Polyendocrine Syndrome Type 1","volume":"102","author":"Orlova","year":"2017","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"680334","DOI":"10.3389\/fimmu.2021.680334","article-title":"One Gene, Many Facets: Multiple Immune Pathway Dysregulation in SOCS1 Haploinsufficiency","volume":"12","author":"Gabrielyan","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"5341","DOI":"10.1038\/s41467-020-18925-4","article-title":"Early-onset autoimmunity associated with SOCS1 haploinsufficiency","volume":"11","author":"Hadjadj","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1016\/j.jaci.2020.07.033","article-title":"Immune dysregulation and multisystem inflammatory syndrome in children (MIS-C) in individuals with haploinsufficiency of SOCS1","volume":"146","author":"Lee","year":"2020","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1007\/s10875-023-01495-7","article-title":"Insights into the expanding intestinal phenotypic spectrum of SOCS1 haploinsufficiency and therapeutic options","volume":"43","author":"Rodari","year":"2023","journal-title":"J. Clin. Immunol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1766","DOI":"10.1007\/s10875-022-01346-x","article-title":"SOCS1 Haploinsufficiency Presenting as Severe Enthesitis, Bone Marrow Hypocellularity, and Refractory Thrombocytopenia in a Pediatric Patient with Subsequent Response to JAK Inhibition","volume":"42","author":"Michniacki","year":"2022","journal-title":"J. Clin. Immunol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1038\/s41586-020-2265-1","article-title":"Whole-genome sequencing of a sporadic primary immunodeficiency cohort","volume":"583","author":"Thaventhiran","year":"2020","journal-title":"Nature"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.ajhg.2010.01.028","article-title":"Human ITCH E3 Ubiquitin Ligase Deficiency Causes Syndromic Multisystem Autoimmune Disease","volume":"86","author":"Lohr","year":"2010","journal-title":"Am. J. Hum. Genet."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.1002\/ajmg.a.61169","article-title":"Biallelic human ITCH variants causing a multisystem disease with dysmorphic features: A second report","volume":"179","author":"Brittain","year":"2019","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2885","DOI":"10.1016\/j.jaip.2021.04.010","article-title":"Immune dysregulation in human ITCH deficiency successfully treated with hematopoietic cell transplantation","volume":"9","author":"Patel","year":"2021","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Eni-Aganga, I., Lanaghan, Z.M., Balasubramaniam, M., Dash, C., and Pandhare, J. (2021). PROLIDASE: A Review from Discovery to its Role in Health and Disease. Front. Mol. Biosci., 8.","DOI":"10.3389\/fmolb.2021.723003"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Spodenkiewicz, M., Spodenkiewicz, M., Cleary, M., Massier, M., Fitsialos, G., Cottin, V., Jouret, G., Poirsier, C., Doco-Fenzy, M., and L\u00e8bre, A.S. (2020). Clinical Genetics of Prolidase Deficiency: An Updated Review. Biology, 9.","DOI":"10.3390\/biology9050108"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1111\/pde.14890","article-title":"A case of prolidase deficiency in a male patient","volume":"39","author":"Haller","year":"2022","journal-title":"Pediatr. Dermatol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1111\/pde.15413","article-title":"Expanding the clinical and immunological phenotype of prolidase deficiency: A case report","volume":"41","author":"Basu","year":"2024","journal-title":"Pediatr. Dermatol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1002\/ajmg.a.63137","article-title":"Prolidase deficiency: A novel PEPD missense variant in exon 2","volume":"191","author":"Ido","year":"2023","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/01.ASW.0000792912.44120.64","article-title":"Prolidase Deficiency Causing Recalcitrant Leg Ulcerations in Siblings","volume":"34","author":"Hajjar","year":"2021","journal-title":"Adv. Skin Wound Care"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1126\/science.1243292","article-title":"Phosphoinositide 3-kinase \u03b4 gene mutation predisposes to respiratory infection and airway damage","volume":"342","author":"Angulo","year":"2013","journal-title":"Science"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2537","DOI":"10.1084\/jem.20141759","article-title":"Heterozygous splice mutation in PIK3R1 causes human immunodeficiency with lymphoproliferation due to dominant activation of PI3K","volume":"211","author":"Lucas","year":"2014","journal-title":"J. Exp. Med."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1007\/s12016-019-08738-9","article-title":"Clinical, Immunological, and Genetic Features in Patients with Activated PI3K\u03b4 Syndrome (APDS): A Systematic Review","volume":"59","author":"Jamee","year":"2020","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.jaci.2016.03.022","article-title":"Clinical and immunologic phenotype associated with activated phosphoinositide 3-kinase \u03b4 syndrome 2: A cohort study","volume":"138","author":"Elkaim","year":"2016","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/j.jaci.2016.06.021","article-title":"Clinical spectrum and features of activated phosphoinositide 3-kinase \u03b4 syndrome: A large patient cohort study","volume":"139","author":"Coulter","year":"2017","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1080\/08820139.2020.1863982","article-title":"The First Iranian Cohort of Pediatric Patients with Activated Phosphoinositide 3-Kinase-\u03b4 (PI3K\u03b4) Syndrome (APDS)","volume":"51","author":"Fekrvand","year":"2022","journal-title":"Immunol. Investig."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/s13223-020-00420-6","article-title":"Activated phosphoinositide 3-kinase delta syndrome 1 and 2 (APDS 1 and APDS 2): Similarities and differences based on clinical presentation in two boys","volume":"16","author":"Ewertowska","year":"2020","journal-title":"Allergy Asthma Clin. Immunol. Off. J. Can. Soc. Allergy Clin. Immunol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"48","DOI":"10.18176\/jiaci.0205","article-title":"Two Faces of LRBA Deficiency in Siblings: Hypogammaglobulinemia and Normal Immunoglobulin Levels","volume":"28","author":"Azizi","year":"2018","journal-title":"J. Investig. Allergol. Clin. Immunol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.clim.2019.04.011","article-title":"Bone marrow transplantation with Favorable outcome in three patients with LPS-responsive beige-like anchor (LRBA) deficiency","volume":"203","author":"Okur","year":"2019","journal-title":"Clin. Immunol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"103442","DOI":"10.1016\/j.autrev.2023.103442","article-title":"Autoimmune lymphoproliferative syndrome: A disorder of immune dysregulation","volume":"22","author":"Paskiewicz","year":"2023","journal-title":"Autoimmun. Rev."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1007\/s11882-014-0462-4","article-title":"Autoimmune lymphoproliferative syndrome: An update and review of the literature","volume":"14","author":"Shah","year":"2014","journal-title":"Curr. Allergy Asthma Rep."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1016\/j.jaci.2018.07.020","article-title":"Jakinibs for the Treatment of Immunodysregulation in Patients with Gain of Function STAT1 or STAT3 Mutations","volume":"142","author":"Forbes","year":"2018","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1038\/nm.3746","article-title":"Autosomal dominant immune dysregulation syndrome in humans with CTLA4 mutations","volume":"20","author":"Schubert","year":"2014","journal-title":"Nat. Med."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"235","DOI":"10.23822\/EurAnnACI.1764-1489.22","article-title":"New therapeutic approach by sirolimus for enteropathy treatment in patients with LRBA deficiency","volume":"49","author":"Azizi","year":"2017","journal-title":"Eur. Ann. Allergy Clin. Immunol."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/13\/3\/259\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:15:04Z","timestamp":1760105704000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/13\/3\/259"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,17]]},"references-count":106,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,3]]}},"alternative-id":["pathogens13030259"],"URL":"https:\/\/doi.org\/10.3390\/pathogens13030259","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,17]]}}}