RESUMEN

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.

Asunto(s)

Factores de Transcripción Forkhead , Enfermedades Genéticas Ligadas al Cromosoma X , Linfocitos T Reguladores , Humanos , Turquía , Masculino , Preescolar , Factores de Transcripción Forkhead/genética , Factores de Transcripción Forkhead/metabolismo , Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Enfermedades Genéticas Ligadas al Cromosoma X/inmunología , Enfermedades Genéticas Ligadas al Cromosoma X/terapia , Linfocitos T Reguladores/inmunología , Lactante , Femenino , Niño , Diabetes Mellitus Tipo 1/inmunología , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/congénito , Enfermedades del Sistema Inmune/diagnóstico , Enfermedades del Sistema Inmune/genética , Enfermedades del Sistema Inmune/terapia , Enfermedades del Sistema Inmune/congénito , Autoinmunidad , Adolescente , Diarrea

Asunto(s)

Trasplante de Células Madre Hematopoyéticas , Inmunodeficiencia Combinada Grave , Humanos , Inmunodeficiencia Combinada Grave/terapia , Inmunodeficiencia Combinada Grave/diagnóstico , Inmunodeficiencia Combinada Grave/genética , Masculino , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico , Enfermedades Genéticas Ligadas al Cromosoma X/terapia , Lactante , Diabetes Mellitus Tipo 1/congénito , Diarrea , Enfermedades del Sistema Inmune/congénito

RESUMEN

Inactivating mutations of Foxp3, the master regulator of regulatory T cell development and function, lead to immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome in mice and humans. IPEX is a fatal autoimmune disease, with allogeneic stem cell transplant being the only available therapy. In this study, we report that a single dose of adeno-associated virus (AAV)-IL-27 to young mice with naturally occurring Foxp3 mutation (Scurfy mice) substantially ameliorates clinical symptoms, including growth retardation and early fatality. Correspondingly, AAV-IL-27 gene therapy significantly prevented naive T cell activation, as manifested by downregulation of CD62L and upregulation of CD44, and immunopathology typical of IPEX. Because IL-27 is known to induce IL-10, a key effector molecule of regulatory T cells, we evaluated the contribution of IL-10 induction by crossing IL-10-null allele to Scurfy mice. Although IL-10 deficiency does not affect the survival of Scurfy mice, it largely abrogated the therapeutic effect of AAV-IL-27. Our study revealed a major role for IL-10 in AAV-IL-27 gene therapy and demonstrated that IPEX is amenable to gene therapy.

Asunto(s)

Factores de Transcripción Forkhead , Enfermedades Genéticas Ligadas al Cromosoma X , Terapia Genética , Mutación de Línea Germinal , Interleucina-10 , Linfocitos T Reguladores , Animales , Factores de Transcripción Forkhead/genética , Ratones , Interleucina-10/genética , Interleucina-10/inmunología , Terapia Genética/métodos , Linfocitos T Reguladores/inmunología , Enfermedades Genéticas Ligadas al Cromosoma X/terapia , Enfermedades Genéticas Ligadas al Cromosoma X/inmunología , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Interleucinas/inmunología , Interleucinas/genética , Diarrea/genética , Diarrea/terapia , Diarrea/inmunología , Enfermedades Intestinales/inmunología , Enfermedades Intestinales/genética , Enfermedades Intestinales/terapia , Dependovirus/genética , Ratones Endogámicos C57BL , Enfermedades del Sistema Inmune/inmunología , Enfermedades del Sistema Inmune/terapia , Enfermedades del Sistema Inmune/genética , Enfermedades del Sistema Inmune/congénito , Diabetes Mellitus Tipo 1/inmunología , Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/congénito , Ratones Noqueados , Activación de Linfocitos/inmunología , Humanos , Interleucina-27/genética

Asunto(s)

Terapia Genética , Diagnóstico Prenatal , Humanos , Embarazo , Diagnóstico Prenatal/métodos , Femenino , Terapia Genética/métodos , Pruebas Genéticas/métodos , Mutación , Enfermedades del Sistema Inmune/terapia , Enfermedades del Sistema Inmune/inmunología , Enfermedades del Sistema Inmune/congénito , Terapias Fetales/métodos

RESUMEN

Regulatory T cell (Treg) deficiency leads to immune dysregulation, polyendocrinopathy, enteropathy, and X-linked (IPEX) syndrome, which is a CD4+ T cell-driven autoimmune disease in both humans and mice. Despite understanding the molecular and cellular characteristics of IPEX syndrome, new treatment options have remained elusive. Here, we hypothesized that salvianolic acid B (Sal B), one of the main active ingredients of Salvia miltiorrhiza, can protect against immune disorders induced by Treg deficiency. To examine whether Sal B can inhibit Treg deficiency-induced autoimmunity, Treg-deficient scurfy (SF) mice with a mutation in forkhead box protein 3 were treated with different doses of Sal B. Immune cells, inflammatory cell infiltration, and cytokines were evaluated by flow cytometry, hematoxylin and eosin staining and enzyme-linked immunosorbent assay Kits, respectively. Moreover, RNA sequencing, western blot, and real-time PCR were adopted to investigate the molecular mechanisms of action of Sal B. Sal B prolonged lifespan and reduced inflammation in the liver and lung of SF mice. Moreover, Sal B decreased plasma levels of several inflammatory cytokines, such as IL-2, IFN-γ, IL-4, TNF-α, and IL-6, in SF mice. By analyzing the transcriptomics of livers, we determined the signaling pathways, especially the IL-2-signal transducer and activator of transcription 5 (STAT5) signaling pathway, which were associated with Treg deficiency-induced autoimmunity. Remarkably, Sal B reversed the expression of gene signatures related to the IL-2-STAT5 signaling pathway in vitro and in vivo. Sal B prolongs survival and inhibits lethal inflammation in SF mice through the IL-2-STAT5 axis. Our findings may inspire novel drug discovery efforts aimed at treating IPEX syndrome.

Asunto(s)

Autoinmunidad , Benzofuranos , Interleucina-2 , Factor de Transcripción STAT5 , Transducción de Señal , Linfocitos T Reguladores , Animales , Factor de Transcripción STAT5/metabolismo , Ratones , Linfocitos T Reguladores/efectos de los fármacos , Benzofuranos/farmacología , Transducción de Señal/efectos de los fármacos , Interleucina-2/metabolismo , Autoinmunidad/efectos de los fármacos , Ratones Endogámicos C57BL , Citocinas/metabolismo , Masculino , Enfermedades Genéticas Ligadas al Cromosoma X , Diabetes Mellitus Tipo 1/congénito , Diarrea , Enfermedades del Sistema Inmune/congénito , Depsidos

Asunto(s)

Anticuerpos Monoclonales Humanizados , Humanos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Masculino , Enfermedades Genéticas Ligadas al Cromosoma X/tratamiento farmacológico , Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico , Fármacos Gastrointestinales/uso terapéutico , Resultado del Tratamiento , Diabetes Mellitus Tipo 1/congénito , Diarrea , Enfermedades del Sistema Inmune/congénito

RESUMEN

A 19-year-old, G1P0, pregnant person was referred at 20w2d gestation for evaluation due to non-immune hydrops fetalis (NIHF), which was confirmed at the time of evaluation. Amniocentesis was performed at 20 w4d, and FISH, karyotype, chromosomal microarray, and exome sequencing (ES) were ordered. Trio ES identified a novel hemizygous c.142 C > T (p.Arg48*; maternally inherited) variant in the FOXP3 gene, resulting in a premature termination codon and establishing the diagnosis of immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome. Intrauterine fetal demise (IUFD) was diagnosed at 21w3d. CVS was performed at 12w1d in a subsequent pregnancy (male fetus) and the known familial variant was identified. NIHF was identified at 18w1d. Ultrasound at 19w2d revealed IUFD. This is the first report of this variant in a diagnosis of IPEX syndrome, presenting with NIHF and male fetal demise. Genotype-phenotype correlations are not available in many cases of IPEX syndrome, as the same genotype can be present with variable severity in different individuals. Given the near identical presentations in this family, we anticipate a more severe phenotype with this variant. We propose a novel variant resulting in an early premature termination codon as an explanation for the severe presentation of IPEX syndrome in two successive fetuses in this family.

Asunto(s)

Codón sin Sentido , Diabetes Mellitus Tipo 1/congénito , Diarrea , Enfermedades Genéticas Ligadas al Cromosoma X , Hidropesía Fetal , Enfermedades del Sistema Inmune/congénito , Embarazo , Femenino , Humanos , Masculino , Adulto Joven , Adulto , Hidropesía Fetal/diagnóstico por imagen , Hidropesía Fetal/genética , Muerte Fetal , Factores de Transcripción Forkhead/genética

RESUMEN

OBJECTIVE: To analyze the clinical characteristics of three patients with Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome. METHODS: Three patients with IPEX syndrome diagnosed at the Children's Hospital of Fudan University from January 24, 2013 to July 29, 2019 were selected as the study subjects. Their clinical features, laboratory investigations and results of genetic testing were summarized. Treatment and prognosis were also explored. RESULTS: All of the three children had developed the disorder during infancy. One child had initial features including diabetes and diabetic ketoacidosis, whilst the other two had initiated by diarrhea. All patients had gastrointestinal involvement, and one was diagnosed as very early onset inflammatory bowel disease by colonoscopy and biopsy. Two children also had endocrine glands involvement. One child had manifested type 1 diabetes and positivity for thyroglobulin and thyroid peroxidase antibodies, though his thyroid function had remained normal. Another one had hypothyroidism and was treated by levothyroxine. Genetic testing revealed that all children had harbored missense variants of the FOXP3 gene, including c.1222G>A (p.V408M), c.767T>C (p.M256T) and c.1021A>G (p.T341A). The clinical symptoms of one patient were alleviated following allogeneic hematopoietic stem cell transplantation. One patient was stable after treatment with infliximab plus insulin, and one child had died of refractory septic shock and multiple organ dysfunction syndrome at 3 months old. CONCLUSION: FOXP3 gene variant-associated IPEX syndrome may have very early onset and diverse clinical manifestations. For male patients with infantile onset chronic diarrhea, multiple endocrine or multiple system involvement, genetic testing is recommended, which may facilitate early diagnosis, treatment and genetic counseling.

Asunto(s)

Diabetes Mellitus Tipo 1/congénito , Enfermedades Genéticas Ligadas al Cromosoma X , Enfermedades del Sistema Inmune/congénito , Enfermedades Intestinales , Niño , Humanos , Masculino , Lactante , Diarrea/genética , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico , Enfermedades Intestinales/genética , Factores de Transcripción Forkhead/genética , Mutación

RESUMEN

In the past 2 decades, a significant number of studies have been published describing the molecular and clinical aspects of immune dysregulation polyendocrinopathy enteropathy X-linked (IPEX) syndrome. These studies have refined our knowledge of this rare yet prototypic genetic autoimmune disease, advancing the diagnosis, broadening the clinical spectrum, and improving our understanding of the underlying immunologic mechanisms. Despite these advances, Forkhead box P3 mutations have devastating consequences, and treating patients with IPEX syndrome remains a challenge, even with safer strategies for hematopoietic stem cell transplantation and gene therapy becoming a promising reality. The aim of this review was to highlight novel features of the disease to further advance awareness and improve the diagnosis and treatment of patients with IPEX syndrome.

Asunto(s)

Diabetes Mellitus Tipo 1/congénito , Enfermedades Genéticas Ligadas al Cromosoma X , Enfermedades del Sistema Inmune , Enfermedades del Sistema Inmune/congénito , Enfermedades Intestinales , Poliendocrinopatías Autoinmunes , Humanos , Linfocitos T Reguladores , Diarrea , Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Enfermedades Genéticas Ligadas al Cromosoma X/terapia , Enfermedades Intestinales/diagnóstico , Enfermedades Intestinales/genética , Enfermedades del Sistema Inmune/diagnóstico , Enfermedades del Sistema Inmune/genética , Enfermedades del Sistema Inmune/terapia , Mutación , Factores de Transcripción Forkhead/genética , Poliendocrinopatías Autoinmunes/diagnóstico , Poliendocrinopatías Autoinmunes/genética , Poliendocrinopatías Autoinmunes/terapia

RESUMEN

Los errores innatos de la inmunidad (EII), antes llamados inmunodeficiencias primarias (IDP), son un grupo heterogéneo de trastornos genéticos con defectos en uno o más componentes del sistema inmune. Los pacientes afectados por EII presentan aumentada susceptibilidad a microorganismos únicos o múltiples que se manifestará con infecciones recurrentes de diferente tipo y gravedad dependiendo del tipo de la localización del defecto. La prevención de infecciones es uno de los pilares fundamentales en el abordaje integral de los pacientes con EII. En este trabajo se resumen las conclusiones consensuadas en el Grupo de Trabajo de Inmunología Pediátrica de la Sociedad Argentina de Pediatría, sobre la base de la revisión de la evidencia disponible, respecto a los principios esenciales para el cuidado, la prevención de infecciones y la quimioprofilaxis en los errores innatos de la inmunidad para la orientación del pediatra y especialista dedicados al seguimiento de estas enfermedades.

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Inborn errors of immunity, previously named primary immunodeficiency are a heterogeneous group of genetic defects of different components of the immune system. Patients present high susceptibility to an only or several microorganisms, developing recurrent infections; the severity is related to the specific genetic type of immunity defect. The main strategy on the management of these illness is the prevention of infections. These consensus guidelines made by the Pediatric Immunology Work Group of Sociedad Argentina de Pediatría, givese main approaches of infection prevention in order to provide a useful tool for all practitioners who are involved in the management of these patients, based on scientific evidence and broad consensus of a specialized panel expert.

Asunto(s)

Humanos , Niño , Quimioprevención , Enfermedades del Sistema Inmune/congénito

RESUMEN

Background: Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare disorder of the immune regulatory system caused by forkhead box P3 (FOXP3) mutations. Abnormal numbers or functions of regulatory T (Treg) cells account for the various autoimmune symptoms. We aimed to explore the molecular genetics and phenotypic spectra of patients with atypical IPEX syndrome in China. Methods: We analyzed the molecular, clinical and immune phenotype characteristics of five Chinese patients with FOXP3 mutations. Results: We summarized the molecular and phenotypic features of five patients with FOXP3 mutations, including two novel mutations. Four of the five patients displayed atypical phenotypes, and one developed immune-related peripheral neuropathy. Three of the five patients showed normal frequencies of Treg cells, but the proportions of subsets of Treg cells, CD4+ T cells and B cells were out of balance. Conclusions: Our report broadens the understanding of the clinical features of atypical IPEX syndrome. Our detailed analyses of the immunological characteristics of these patients enhance the understanding of the possible mechanisms underlying the clinical manifestations.

Asunto(s)

Factores de Transcripción Forkhead , Poliendocrinopatías Autoinmunes , Diabetes Mellitus Tipo 1/congénito , Diabetes Mellitus Tipo 1/genética , Diarrea/etiología , Diarrea/genética , Factores de Transcripción Forkhead/genética , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Humanos , Enfermedades del Sistema Inmune/congénito , Enfermedades del Sistema Inmune/genética , Enfermedades Intestinales/congénito , Enfermedades Intestinales/genética , Fenotipo , Poliendocrinopatías Autoinmunes/congénito , Poliendocrinopatías Autoinmunes/genética , Síndrome

RESUMEN

Introduction: In recent decades, there has been a growing increase in the diagnosis of patients with inborn errors of the immune system, formerly known as primary immunodeficiency dis-orders (PIDs). Timely diagnosis remains a challenge due to low clinical suspicion and poor edu-cation on the subject. It is estimated that between 70% and 90% of these pathologies remain underdiagnosed in our environment.Objective: The objective of this study is to characterize the demographic and clinical presen-tation of pediatric group patients with inborn errors of the immune system in a Colombian tertiary hospital.Methods: Retrospective descriptive study of 306 patients with a diagnosis of innate errors of the immune system who consulted the PID clinic between 2011 and 2018 in a high-complexity institution in Cali, Colombia.Results: Three-hundred and six patients were included. The median age was 4 years (IQR 2.3–7.7 years), and 59.5% of the patients were male. According to the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency classification for inborn errors of the immune system, the most common group was antibody deficiency in 74.8% (n=229), especially in the age group between 1 and 5 years. The least frequent in our pop-ulation was complement deficiency. Of the warning signs stipulated for these pathologies, the most frequent were the (1) need for intravenous antibiotics (32%), (2) difficulty growing (15.7%), (3) four or more episodes of ear infection (10.8%), and (4) abscesses in organs or cuta-neous abscesses (12.7%). No patient reported two or more episodes of pneumonia or sinusitis, and only 5.8% of the patients received a bone marrow transplant (AU)

Asunto(s)

Humanos , Masculino , Femenino , Preescolar , Niño , Enfermedades del Sistema Inmune/congénito , Atención Terciaria de Salud , Estudios Retrospectivos , Colombia

RESUMEN

Immune dysregulation polyendocrinopathy enteropathy X linked (IPEX) syndrome is an uncurable disease of the immune system, with immune dysregulation that is caused by mutations in FOXP3. Current treatment options, such as pharmacological immune suppression and allogeneic hematopoietic stem cell transplantation, have been beneficial but present limitations, and their life-long consequences are ill-defined. Other similar blood monogenic diseases have been successfully treated using gene transfer in autologous patient cells, thus providing an effective and less invasive therapeutic. Development of gene therapy for patients with IPEX is particularly challenging because successful strategies must restore the complex expression profile of the transcription factor FOXP3, ensuring it is tightly regulated and its cell subset-specific roles are maintained. This review summarizes current efforts toward achieving gene therapy to treat immune dysregulation in IPEX patients.

Asunto(s)

Diabetes Mellitus Tipo 1 , Enfermedades Genéticas Ligadas al Cromosoma X , Enfermedades del Sistema Inmune , Diabetes Mellitus Tipo 1/congénito , Diarrea , Factores de Transcripción Forkhead/genética , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Enfermedades Genéticas Ligadas al Cromosoma X/terapia , Terapia Genética , Humanos , Enfermedades del Sistema Inmune/congénito , Enfermedades del Sistema Inmune/genética , Enfermedades del Sistema Inmune/terapia , Mutación , Linfocitos T Reguladores

RESUMEN

Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare genetic disorder that typically presents in the first year of life with severe diarrhea, autoimmune endocrine disorder, and inflammatory dermatitis, most commonly an eczematous dermatitis. IPEX syndrome is caused by variants in the FOXP3 gene leading to dysregulation of T-regulatory (Treg) cells and an aberrant immune response. Here, we present a case of severe IPEX syndrome diagnosed following whole genome sequencing (WGS) in a 2-week-old boy with bloody mucoid diarrhea, failure to thrive, and a diffuse eczematous dermatitis. As multiple variants of interest were identified with WGS, this case highlights the importance of relating the clinical symptoms to the genetic results.

Asunto(s)

Diabetes Mellitus Tipo 1 , Eccema , Enfermedades Genéticas Ligadas al Cromosoma X , Enfermedades del Sistema Inmune , Enfermedades Intestinales , Poliendocrinopatías Autoinmunes , Diabetes Mellitus Tipo 1/congénito , Diarrea/diagnóstico , Diarrea/genética , Factores de Transcripción Forkhead/genética , Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Humanos , Enfermedades del Sistema Inmune/congénito , Enfermedades del Sistema Inmune/diagnóstico , Enfermedades del Sistema Inmune/genética , Enfermedades Intestinales/genética , Masculino , Técnicas de Diagnóstico Molecular , Mutación , Poliendocrinopatías Autoinmunes/diagnóstico , Poliendocrinopatías Autoinmunes/genética , Síndrome

RESUMEN

BACKGROUND: Most patients with childhood-onset immune dysregulation, polyendocrinopathy, and enteropathy have no genetic diagnosis for their illness. These patients may undergo empirical immunosuppressive treatment with highly variable outcomes. OBJECTIVE: We sought to determine the genetic basis of disease in patients referred with Immune dysregulation, polyendocrinopathy, enteropathy, X-linked-like (IPEX-like) disease, but with no mutation in FOXP3; then to assess consequences of genetic diagnoses for clinical management. METHODS: Genomic DNA was sequenced using a panel of 462 genes implicated in inborn errors of immunity. Candidate mutations were characterized by genomic, transcriptional, and (for some) protein analysis. RESULTS: Of 123 patients with FOXP3-negative IPEX-like disease, 48 (39%) carried damaging germline mutations in 1 of the following 27 genes: AIRE, BACH2, BCL11B, CARD11, CARD14, CTLA4, IRF2BP2, ITCH, JAK1, KMT2D, LRBA, MYO5B, NFKB1, NLRC4, POLA1, POMP, RAG1, SH2D1A, SKIV2L, STAT1, STAT3, TNFAIP3, TNFRSF6/FAS, TNRSF13B/TACI, TOM1, TTC37, and XIAP. Many of these genes had not been previously associated with an IPEX-like diagnosis. For 42 of the 48 patients with genetic diagnoses, knowing the critical gene could have altered therapeutic management, including recommendations for targeted treatments and for or against hematopoietic cell transplantation. CONCLUSIONS: Many childhood disorders now bundled as "IPEX-like" disease are caused by individually rare, severe mutations in immune regulation genes. Most genetic diagnoses of these conditions yield clinically actionable findings. Barriers are lack of testing or lack of repeat testing if older technologies failed to provide a diagnosis.

Asunto(s)

Diabetes Mellitus Tipo 1/congénito , Diarrea/genética , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Enfermedades del Sistema Inmune/congénito , Adolescente , Niño , Preescolar , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/terapia , Diarrea/diagnóstico , Diarrea/terapia , Femenino , Expresión Génica , Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico , Enfermedades Genéticas Ligadas al Cromosoma X/terapia , Trasplante de Células Madre Hematopoyéticas , Humanos , Enfermedades del Sistema Inmune/diagnóstico , Enfermedades del Sistema Inmune/genética , Enfermedades del Sistema Inmune/terapia , Lactante , Recién Nacido , Masculino , Mutación

RESUMEN

Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is an early onset systemic autoimmune genetic disorder caused by mutation of the forkhead box protein 3 (FOXP3) gene. Enteropathy, endocrinopathy and skin manifestations are considered the classic triad of IPEX syndrome. However, patients with IPEX syndrome display a variety of phenotypes including life threatening multi-organ autoimmunity. Here, we present the case of two siblings with IPEX syndrome with the same hemizygous mutation, but with different types of symptomology at onset of the disease.

Asunto(s)

Diabetes Mellitus Tipo 1 , Enfermedades Genéticas Ligadas al Cromosoma X , Enfermedades Intestinales , Poliendocrinopatías Autoinmunes , Diabetes Mellitus Tipo 1/congénito , Diarrea/genética , Factores de Transcripción Forkhead/genética , Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Humanos , Enfermedades del Sistema Inmune/congénito , Enfermedades Intestinales/diagnóstico , Enfermedades Intestinales/genética , Mutación , Poliendocrinopatías Autoinmunes/diagnóstico , Poliendocrinopatías Autoinmunes/genética , Hermanos , Síndrome

Asunto(s)

Autoanticuerpos/sangre , Diabetes Mellitus Tipo 1/congénito , Diarrea/sangre , Enfermedades Genéticas Ligadas al Cromosoma X/sangre , Enfermedades del Sistema Inmune/congénito , Síndrome de Isaacs/sangre , Canales de Potasio con Entrada de Voltaje/inmunología , Adolescente , Niño , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/inmunología , Diabetes Mellitus Tipo 1/terapia , Diarrea/genética , Diarrea/inmunología , Diarrea/terapia , Factores de Transcripción Forkhead/genética , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Enfermedades Genéticas Ligadas al Cromosoma X/inmunología , Enfermedades Genéticas Ligadas al Cromosoma X/terapia , Trasplante de Células Madre Hematopoyéticas , Humanos , Enfermedades del Sistema Inmune/sangre , Enfermedades del Sistema Inmune/genética , Enfermedades del Sistema Inmune/inmunología , Enfermedades del Sistema Inmune/terapia , Recién Nacido , Síndrome de Isaacs/genética , Síndrome de Isaacs/inmunología , Síndrome de Isaacs/terapia , Masculino , Mutación

Asunto(s)

Diabetes Mellitus Tipo 1/congénito , Diarrea/inmunología , Enfermedades Genéticas Ligadas al Cromosoma X/inmunología , Enfermedades del Sistema Inmune/congénito , Síndromes Mielodisplásicos/inmunología , Linfocitos T Reguladores/inmunología , Adolescente , Diabetes Mellitus Tipo 1/inmunología , Humanos , Enfermedades del Sistema Inmune/inmunología , Masculino

RESUMEN

This case describes a patient with immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome with diffuse eczematous dermatitis and severe, intractable pruritus. Despite a bone marrow transplant and immunosuppressive therapy, his skin findings and pruritus persisted. Off-label dupilumab provided significant improvement and almost complete clearance of the dermatitis and pruritus. This is the first known report of dupilumab being used in a patient with IPEX syndrome.

Asunto(s)

Dermatitis Atópica , Eccema , Enfermedades Genéticas Ligadas al Cromosoma X , Anticuerpos Monoclonales Humanizados , Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/genética , Diabetes Mellitus Tipo 1/congénito , Diarrea , Eccema/tratamiento farmacológico , Eccema/genética , Factores de Transcripción Forkhead/genética , Enfermedades Genéticas Ligadas al Cromosoma X/tratamiento farmacológico , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Humanos , Enfermedades del Sistema Inmune/congénito , Mutación , Prurito/tratamiento farmacológico , Prurito/genética

RESUMEN

Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare immune deficiency with a broad clinical presentation. IPEX syndrome causes dysfunctional regulatory T cells, increasing the risk of autoimmune diseases. In this case report, we describe a 7-year-old boy with lymphocytic interstitial pneumonia and bullous pemphigoid who was recently diagnosed with IPEX syndrome.

Asunto(s)

Enfermedades Pulmonares Intersticiales , Penfigoide Ampolloso , Niño , Diabetes Mellitus Tipo 1/congénito , Diarrea , Factores de Transcripción Forkhead , Enfermedades Genéticas Ligadas al Cromosoma X , Humanos , Enfermedades del Sistema Inmune/congénito , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/genética , Masculino , Penfigoide Ampolloso/diagnóstico , Penfigoide Ampolloso/tratamiento farmacológico , Penfigoide Ampolloso/genética , Linfocitos T Reguladores