Diverse Clinical and Immunological Profiles in Patients with IPEX Syndrome: a Multicenter Analysis from Turkey

• Published in: Journal of clinical immunology Vol. 45; no. 1; p. 9
• Main Authors: Bekis Bozkurt, Hayrunnisa, Bayram Catak, Feyza, Sahin, Ali, Yalcin Gungoren, Ezgi, Gemici Karaarslan, Betul, Yakici, Nalan, Yorgun Altunbas, Melek, Catak, Mehmet Cihangir, Can, Salim, Amirov, Razin, Bozkurt, Selcen, Ozturk, Necmiye, Bilgic Eltan, Sevgi, Kasap, Nurhan, Bal Cetinkaya, Fatma, Orhan, Fazil, Arga, Mustafa, Cavkaytar, Ozlem, Kiykim, Ayca, Karakoc-Aydiner, Elif, Ozen, Ahmet, Baris, Safa
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.12.2025; Springer Nature B.V
• Subjects: Adolescent; Age; Autoimmunity; Biomedical and Life Sciences; Biomedicine; CD25 antigen; Cell proliferation; Child; Child, Preschool; CTLA-4 protein; Diabetes mellitus; Diabetes Mellitus, Type 1 - congenital; Diabetes Mellitus, Type 1 - diagnosis; Diabetes Mellitus, Type 1 - genetics; Diabetes Mellitus, Type 1 - immunology; Diagnosis; Diarrhea; Eczema; Eosinophilia; Female; Forkhead Transcription Factors - genetics; Forkhead Transcription Factors - metabolism; Foxp3 protein; Genetic Diseases, X-Linked - diagnosis; Genetic Diseases, X-Linked - genetics; Genetic Diseases, X-Linked - immunology; Genetic Diseases, X-Linked - therapy; Helper cells; Hematopoietic stem cells; Humans; Immune System Diseases - congenital; Immune System Diseases - diagnosis; Immune System Diseases - genetics; Immune System Diseases - therapy; Immunology; Immunosuppressive agents; Infant; Infectious Diseases; Internal Medicine; Lymphocytes T; Male; Medical Microbiology; Medical treatment; Patients; Rapamycin; Stem cell transplantation; T-Lymphocytes, Regulatory - immunology; Turkey; Turkey; Atypical phenotype; IPEX syndrome; Immunosuppressants; Outcome; Hematopoietic stem cell transplantation
• ISSN: 0271-9142; 1573-2592; 1573-2592
• DOI: 10.1007/s10875-024-01791-w

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 (cT FH ) 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 T H 2-like skewing accompanied by reduced T H 17-like responses was observed in cT FH 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.