Hayrunnisa Bekis Bozkurt, Feyza Bayram Catak, Ali Sahin, Ezgi Yalcin Gungoren, Betul Gemici Karaarslan, Nalan Yakici, Melek Yorgun Altunbas, Mehmet Cihangir Catak, Salim Can, Razin Amirov, Selcen Bozkurt, Necmiye Ozturk, Sevgi Bilgic Eltan, Nurhan Kasap, Fatma Bal Cetinkaya, Fazil Orhan, Mustafa Arga, Ozlem Cavkaytar, Ayca Kiykim, Elif Karakoc-Aydiner, Ahmet Ozen, Safa Baris
{"title":"IPEX 综合征患者的不同临床和免疫学特征：土耳其多中心分析","authors":"Hayrunnisa Bekis Bozkurt, Feyza Bayram Catak, Ali Sahin, Ezgi Yalcin Gungoren, Betul Gemici Karaarslan, Nalan Yakici, Melek Yorgun Altunbas, Mehmet Cihangir Catak, Salim Can, Razin Amirov, Selcen Bozkurt, Necmiye Ozturk, Sevgi Bilgic Eltan, Nurhan Kasap, Fatma Bal Cetinkaya, Fazil Orhan, Mustafa Arga, Ozlem Cavkaytar, Ayca Kiykim, Elif Karakoc-Aydiner, Ahmet Ozen, Safa Baris","doi":"10.1007/s10875-024-01791-w","DOIUrl":null,"url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose</h3><p>Immunodysregulation, Polyendocrinopathy, Enteropathy, and X-linked syndrome (IPEX), caused by pathogenic <i>FOXP3</i> variants, is a rare autoimmune disorder with diverse clinical features, including early-onset diabetes, eczema, and enteropathy. Atypical cases show milder symptoms and unique signs, requiring different treatments. Therefore, there are ambiguities in the accurate diagnosis and management of IPEX. We sought to present clinical, genetic, and immunological assessments of 12 IPEX patients with long-term follow-up to facilitate the diagnosis and management of the disease.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Clinical findings and treatment options of the patients were collected over time. Lymphocyte subpopulations, protein expressions, regulatory T (Treg) and circulating T follicular helper (cT<sub>FH</sub>) cells, and T-cell proliferation were analyzed.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Predominant presentations included autoimmunity (91.6%), failure to thrive (66.7%), and eczema (58.3%). There were four classical and eight atypical IPEX individuals. Allergic manifestations were more common in atypical patients. Notably, chronic diarrhea demonstrated heightened severity compared to other manifestations. Four patients (33.3%) demonstrated eosinophilia, and nine (75%) showed high serum IgE levels. Most patients exhibited normal percentages of Treg cells with reduced CD25, FOXP3, and CTLA-4 expressions, corrected after hematopoietic stem cell transplantation (HSCT). Compared to healthy controls, the T<sub>H</sub>2-like skewing accompanied by reduced T<sub>H</sub>17-like responses was observed in cT<sub>FH</sub> and Treg cells of patients. Overall, nine patients (75%) received immunosuppressants (ISs), and six (50%) underwent HSCT, which was the only treatment revealing sustained control. Sirolimus was used in six patients and showed better control than other ISs.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>The first cohort from Turkey with long-term follow-up results, comparing typical and atypical cases, provides insights into the outcomes of different therapeutic modalities and T- cell subtype changes in IPEX syndrome.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"29 1","pages":""},"PeriodicalIF":7.2000,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Diverse Clinical and Immunological Profiles in Patients with IPEX Syndrome: a Multicenter Analysis from Turkey\",\"authors\":\"Hayrunnisa Bekis Bozkurt, Feyza Bayram Catak, Ali Sahin, Ezgi Yalcin Gungoren, Betul Gemici Karaarslan, Nalan Yakici, Melek Yorgun Altunbas, Mehmet Cihangir Catak, Salim Can, Razin Amirov, Selcen Bozkurt, Necmiye Ozturk, Sevgi Bilgic Eltan, Nurhan Kasap, Fatma Bal Cetinkaya, Fazil Orhan, Mustafa Arga, Ozlem Cavkaytar, Ayca Kiykim, Elif Karakoc-Aydiner, Ahmet Ozen, Safa Baris\",\"doi\":\"10.1007/s10875-024-01791-w\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<h3 data-test=\\\"abstract-sub-heading\\\">Purpose</h3><p>Immunodysregulation, Polyendocrinopathy, Enteropathy, and X-linked syndrome (IPEX), caused by pathogenic <i>FOXP3</i> variants, is a rare autoimmune disorder with diverse clinical features, including early-onset diabetes, eczema, and enteropathy. Atypical cases show milder symptoms and unique signs, requiring different treatments. Therefore, there are ambiguities in the accurate diagnosis and management of IPEX. We sought to present clinical, genetic, and immunological assessments of 12 IPEX patients with long-term follow-up to facilitate the diagnosis and management of the disease.</p><h3 data-test=\\\"abstract-sub-heading\\\">Methods</h3><p>Clinical findings and treatment options of the patients were collected over time. Lymphocyte subpopulations, protein expressions, regulatory T (Treg) and circulating T follicular helper (cT<sub>FH</sub>) cells, and T-cell proliferation were analyzed.</p><h3 data-test=\\\"abstract-sub-heading\\\">Results</h3><p>Predominant presentations included autoimmunity (91.6%), failure to thrive (66.7%), and eczema (58.3%). There were four classical and eight atypical IPEX individuals. Allergic manifestations were more common in atypical patients. Notably, chronic diarrhea demonstrated heightened severity compared to other manifestations. Four patients (33.3%) demonstrated eosinophilia, and nine (75%) showed high serum IgE levels. Most patients exhibited normal percentages of Treg cells with reduced CD25, FOXP3, and CTLA-4 expressions, corrected after hematopoietic stem cell transplantation (HSCT). Compared to healthy controls, the T<sub>H</sub>2-like skewing accompanied by reduced T<sub>H</sub>17-like responses was observed in cT<sub>FH</sub> and Treg cells of patients. Overall, nine patients (75%) received immunosuppressants (ISs), and six (50%) underwent HSCT, which was the only treatment revealing sustained control. Sirolimus was used in six patients and showed better control than other ISs.</p><h3 data-test=\\\"abstract-sub-heading\\\">Conclusions</h3><p>The first cohort from Turkey with long-term follow-up results, comparing typical and atypical cases, provides insights into the outcomes of different therapeutic modalities and T- cell subtype changes in IPEX syndrome.</p>\",\"PeriodicalId\":15531,\"journal\":{\"name\":\"Journal of Clinical Immunology\",\"volume\":\"29 1\",\"pages\":\"\"},\"PeriodicalIF\":7.2000,\"publicationDate\":\"2024-09-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Clinical Immunology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s10875-024-01791-w\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Clinical Immunology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10875-024-01791-w","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Diverse Clinical and Immunological Profiles in Patients with IPEX Syndrome: a Multicenter Analysis from Turkey
Purpose
Immunodysregulation, Polyendocrinopathy, Enteropathy, and X-linked syndrome (IPEX), caused by pathogenic FOXP3 variants, is a rare autoimmune disorder with diverse clinical features, including early-onset diabetes, eczema, and enteropathy. Atypical cases show milder symptoms and unique signs, requiring different treatments. Therefore, there are ambiguities in the accurate diagnosis and management of IPEX. We sought to present clinical, genetic, and immunological assessments of 12 IPEX patients with long-term follow-up to facilitate the diagnosis and management of the disease.
Methods
Clinical findings and treatment options of the patients were collected over time. Lymphocyte subpopulations, protein expressions, regulatory T (Treg) and circulating T follicular helper (cTFH) cells, and T-cell proliferation were analyzed.
Results
Predominant presentations included autoimmunity (91.6%), failure to thrive (66.7%), and eczema (58.3%). There were four classical and eight atypical IPEX individuals. Allergic manifestations were more common in atypical patients. Notably, chronic diarrhea demonstrated heightened severity compared to other manifestations. Four patients (33.3%) demonstrated eosinophilia, and nine (75%) showed high serum IgE levels. Most patients exhibited normal percentages of Treg cells with reduced CD25, FOXP3, and CTLA-4 expressions, corrected after hematopoietic stem cell transplantation (HSCT). Compared to healthy controls, the TH2-like skewing accompanied by reduced TH17-like responses was observed in cTFH and Treg cells of patients. Overall, nine patients (75%) received immunosuppressants (ISs), and six (50%) underwent HSCT, which was the only treatment revealing sustained control. Sirolimus was used in six patients and showed better control than other ISs.
Conclusions
The first cohort from Turkey with long-term follow-up results, comparing typical and atypical cases, provides insights into the outcomes of different therapeutic modalities and T- cell subtype changes in IPEX syndrome.
期刊介绍：
The Journal of Clinical Immunology publishes impactful papers in the realm of human immunology, delving into the diagnosis, pathogenesis, prognosis, or treatment of human diseases. The journal places particular emphasis on primary immunodeficiencies and related diseases, encompassing inborn errors of immunity in a broad sense, their underlying genotypes, and diverse phenotypes. These phenotypes include infection, malignancy, allergy, auto-inflammation, and autoimmunity. We welcome a broad spectrum of studies in this domain, spanning genetic discovery, clinical description, immunologic assessment, diagnostic approaches, prognosis evaluation, and treatment interventions. Case reports are considered if they are genuinely original and accompanied by a concise review of the relevant medical literature, illustrating how the novel case study advances the field. The instructions to authors provide detailed guidance on the four categories of papers accepted by the journal.
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