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Eystein S. Husebye - One of the best experts on this subject based on the ideXlab platform.
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Oral Tongue Malignancies in Autoimmune Polyendocrine Syndrome Type 1.
Frontiers in endocrinology, 2018Co-Authors: Øyvind Bruserud, Daniela Elena Costea, Saila Laakso, Ben-zion Garty, Eirik Mathisen, Antti Mäkitie, Outi Mäkitie, Eystein S. HusebyeAbstract:Autoimmune Polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) or Autoimmune polyendocrine syndrome type-1 (APS-1) (APECED, OMIM 240300) is a rare, childhood onset, monogenic disease caused by mutations in the Autoimmune Regulator (AIRE) gene. The overall mortality is increased compared to the general population and a major cause of death includes malignant diseases, especially oral and esophageal cancers. We here present a case series of four APS-1 patients with oral tongue cancers, an entity not described in detail previously. Scrutiny of history and clinical phenotypes indicate that chronic mucocutaneous candidiasis and smoking are significant risk factors. Preventive measures and early diagnosis are important to successfully manage this potentially fatal disease.
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autoantibodies against type i interferons as an additional diagnostic criterion for autoimmune polyendocrine syndrome type i
The Journal of Clinical Endocrinology and Metabolism, 2008Co-Authors: Antonella Meloni, Roberto Perniola, Filomena Cetani, Claudio Marcocci, Eystein S. Husebye, Maria Furcas, Alberto Falorni, Mikulas Pura, Anette S B Wolff, Desa LilicAbstract:Context: In autoimmune Polyendocrinopathy syndrome type I (APS-I), mutations in the autoimmune regulator gene (AIRE) impair thymic self-tolerance induction in developing T cells. The ensuing autoimmunity particularly targets ectodermal and endocrine tissues, but chronic candidiasis usually comes first. We recently reported apparently APS-I-specific high-titer neutralizing autoantibodies against type I interferons in 100% of Finnish and Norwegian patients, mainly with two prevalent AIRE truncations. Objectives: Because variability in clinical features and age at onset in APS-I frequently results in unusual presentations, we prospectively checked the diagnostic potential of anti-interferon antibodies in additional APS-I panels with other truncations or rare missense mutations and in disease controls with chronic mucocutaneous candidiasis (CMC) but without either common AIRE mutation. Design: The study was designed to detect autoantibodies against interferon-α2 and interferon-ω in antiviral neutralization as...
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clinical evolution of kearns sayre syndrome with Polyendocrinopathy and respiratory failure
Acta Neurologica Scandinavica, 2007Co-Authors: L Bindoff, Eystein S. Husebye, Petter Schandl Sanaker, O FondenesAbstract:Background - The triad of progressive external ophthalmoplegia, atypical retinal pigmentation and cardiac conduction defects characterizes Kearns-Sayre syndrome (KSS), which is most often caused by a single, large deletion of mitochondrial DNA. Endocrine disease appears to be more common in KSS than in other mitochondrial diseases. Materials, methods and results - A patient presenting with KSS developed Addison's disease, hypothyroidism and glucose intolerance. Thyroid peroxidase antibodies and adrenal 21-hydroxylase antibodies were identified. She developed acute respiratory failure requiring invasive ventilatory support, but improved and currently requires only non-invasive, nocturnal BiPAP treatment. Discussion and conclusion - This case confirms the association of KSS and endocrine dysfunction. Our finding of autoantibodies to thyroid and adrenal glands distinguishes this patient from most other published cases and suggests a potential synergy between the two disease mechanisms. In addition, we demonstrate that respiratory failure can be a treatable event in this disease.
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anti interferon autoantibodies in autoimmune Polyendocrinopathy syndrome type 1
PLOS Medicine, 2006Co-Authors: Anthony Meager, Part Peterson, Eystein S. Husebye, Petra Eskelin, J Perheentupa, Kai Krohn, Kumuthini Visvalingam, Kaidi Moll, Astrid MurumagiAbstract:Background The autoimmune regulator (AIRE) gene influences thymic self-tolerance induction. In autoimmune Polyendocrinopathy syndrome type 1 (APS1; OMIM 240300), recessive AIRE mutations lead to autoimmunity targetting endocrine and other epithelial tissues, although chronic candidiasis usually appears first. Autoimmunity and chronic candidiasis can associate with thymomas as well. Patients with these tumours frequently also have high titre immunoglobulin G autoantibodies neutralising type I interferon (IFN)–α and IFN-ω, which are secreted signalling proteins of the cytokine superfamily involved in both innate and adaptive immunity. Methods and Findings We tested for serum autoantibodies to type I IFNs and other immunoregulatory cytokines using specific binding and neutralisation assays. Unexpectedly, in 60/60 Finnish and 16/16 Norwegian APS1 patients with both AIRE alleles mutated, we found high titre neutralising immunoglobulin G autoantibodies to most IFN-α subtypes and especially IFN-ω (60% homologous to IFN-α)—mostly in the earliest samples. We found lower titres against IFN-β (30% homologous to IFN-α) in 23% of patients; two-thirds of these (from Finland only) also had low titres against the distantly related “type III IFN” (IFN-λ1; alias interleukin-29). However, autoantibodies to the unrelated type II IFN, IFN-γ, and other immunoregulatory cytokines, such as interleukin-10 and interleukin-12, were much rarer and did not neutralise. Neutralising titres against type I IFNs averaged even higher in patients with APS1 than in patients with thymomas. Anti–type I IFN autoantibodies preceded overt candidiasis (and several of the autoimmune disorders) in the informative patients, and persisted for decades thereafter. They were undetectable in unaffected heterozygous relatives of APS1 probands (except for low titres against IFN-λ1), in APS2 patients, and in isolated cases of the endocrine diseases most typical of APS1, so they appear to be APS1-specific. Looking for potentially autoimmunising cell types, we found numerous IFN-α+ antigen-presenting cells—plus strong evidence of local IFN secretion—in the normal thymic medulla (where AIRE expression is strongest), and also in normal germinal centres, where it could perpetuate these autoantibody responses once initiated. IFN-α2 and IFN-α8 transcripts were also more abundant in antigen-presenting cells cultured from an APS1 patient's blood than from age-matched healthy controls. Conclusions These apparently spontaneous autoantibody responses to IFNs, particularly IFN-α and IFN-ω, segregate like a recessive trait; their high “penetrance” is especially remarkable for such a variable condition. Their apparent restriction to APS1 patients implies practical value in the clinic, e.g., in diagnosing unusual or prodromal AIRE-mutant patients with only single components of APS1, and possibly in prognosis if they prove to predict its onset. These autoantibody responses also raise numerous questions, e.g., about the rarity of other infections in APS1. Moreover, there must also be clues to autoimmunising mechanisms/cell types in the hierarchy of preferences for IFN-ω, IFN-α8, IFN-α2, and IFN-β and IFN-λ1.
Part Peterson - One of the best experts on this subject based on the ideXlab platform.
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Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy
Journal of Clinical Immunology, 2015Co-Authors: Kai Kisand, Part PetersonAbstract:Autoimmune Polyendocrinopathy candidiasis ectodermal dystrophy (APECED) is an autosomal recessive disease caused by mutations in the autoimmune regulator ( AIRE ) gene. This review focuses on the clinical and immunological features of APECED, summarizes the current knowledge on the function of AIRE and discusses the importance of autoantibodies in disease diagnosis and prognosis. Additionally, we review the outcome of recent immunomodulatory treatments in APECED patients.
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autoimmune Polyendocrinopathy candidiasis ectodermal dystrophy known and novel aspects of the syndrome
Annals of the New York Academy of Sciences, 2011Co-Authors: Kai Kisand, Part PetersonAbstract:Autoimmune Polyendocrinopathy candidiasis ectodermal dystrophy (APECED) is a monogenic autosomal recessive disease caused by mutations in the autoimmune regulator (AIRE) gene and, as a syndrome, is characterized by chronic mucocutaneous candidiasis and the presentation of various autoimmune diseases. During the last decade, research on APECED and AIRE has provided immunologists with several invaluable lessons regarding tolerance and autoimmunity. This review describes the clinical and immunological features of APECED and discusses emerging alternative models to explain the pathogenesis of the disease.
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mucocutaneous candidiasis and autoimmunity against cytokines in apeced and thymoma patients clinical and pathogenetic implications
European Journal of Immunology, 2011Co-Authors: Kai Kisand, Part Peterson, Anthony Meager, Desa Lilic, Jeanlaurent Casanova, Nick WillcoxAbstract:Much has been learnt about the mechanisms of thymic self-tolerance induction from work on both the rare autosomal recessive disease autoimmune Polyendocrinopathy candidiasis ectodermal dystrophy (APECED) and the autoimmune regulator (AIRE) protein mutated in this disease. Normally, AIRE drives low-level expression of huge numbers of peripheral tissue-specific antigens (TSAgs) in medullary thymic epithelial cells (mTECs), leading to the deletion of TSAg-reactive thymocytes maturing nearby. The very recently discovered neutralizing autoantibodies (autoAbs) against Th17-related cells and cytokines in two autoimmunity-related syndromes associated with AIRE-mutant thymi or AIRE-deficient thymomas help to explain the chronic mucocutaneous candidiasis (CMC) seen in both syndromes. The surprising parallels between these syndromes also demand new hypotheses and research into the consequences of AIRE deficiency and the ensuing autoimmunizing pathways, and suggest more appropriate treatment regimens as discussed in this review.
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PHD finger of autoimmune regulator: An epigenetic link between the histone modifications and tissue-specific antigen expression in thymus
Epigenetics, 2008Co-Authors: Giovanna Musco, Part PetersonAbstract:Methylation of lysine residues on histone H3 tails regulates transcription. A recent addition to the list of known methylated histone binding modules is the plant homeodomain (PHD) finger, which is usually found in nuclear proteins with chromatin-related functions. Autoimmune regulator (AIRE) protein contains two PHD fingers and mutations in AIRE gene cause the monogenic disease autoimmune Polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). AIRE is expressed in thymic medullary epithelial cells where it promotes the expression of tissue-specific antigens. However the mechanism by which AIRE controls gene expression is currently unknown and the function of its domains, in particular of its PHD fingers is still elusive and controversial. In this review we discuss recent works on AIRE PHD finger(s) providing a new link between the status of histone modifications and the regulation of tissue-specific antigen expression in thymus.
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pituitary autoantibodies in autoimmune Polyendocrinopathy candidiasis ectodermal dystrophy apeced
Acta bio-medica : Atenei Parmensis, 2007Co-Authors: Damien T Odwyer, Part Peterson, J Perheentupa, Patrick Mcelduff, Patricia A CrockAbstract:Autoimmune Polyendocrinopathy - candidiasis - ectodermal dystrophy (APECED) is an autosomal recessive disease due to mutations in the AIRE (AutoImmune REgulator) gene. The role of pituitary autoimmunity in APECED is not known.We determined the prevalence of pituitary autoantibodies in a cohort of 67 Finnish patients with APECED from 217 serum samples collected over 26 years by one investigator. Overall, autoantibodies to the 49 kDa cytosolic autoantigen, human pituitary enolase were detected in 39 of the 67 patients (58%). On their first sample, 25 patients had autoantibodies compared to 5 of 68 controls (chi-square, 1df=17.11, p< 0.001; OR=7.32), but subsequently 14 patients seroconverted between 10 and 53 years of age. Once seropositive, all but two of the patients maintained their positive autoantibody status, even over many years. In the current study all but 7 of the 19 patients known to have high titre anti-candidal enolase antibodies had developed autoantibodies directed against human pituitary enolase. Other pituitary autoantibody reactivities were detected against cytosolic proteins of molecular weights 40-, 45-, 60- and 105 kDa in 15%, 16%, 12% and 3% of patients respectively. Autoantibodies to pituitary enolase are markers of neuroendocrine autoimmunity but seem not to be associated with clinical hypopituitarism in APECED patients.
Hans D. Ochs - One of the best experts on this subject based on the ideXlab platform.
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Immune dysregulation, Polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome: A systematic review.
Autoimmunity reviews, 2020Co-Authors: Jae Hyon Park, Hans D. Ochs, Ciriaco A. Piccirillo, Keum Hwa Lee, Bokyoung Jeon, Joon Suk Lee, Heon Yung Gee, Seeun Seo, Dongil Geum, Michael EisenhutAbstract:Abstract Background Immune dysregulation, Polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a monogenic disorder characterized by early onset fatal multi-system autoimmunity due to loss-of-function mutations in the gene encoding the forkhead box P3 (FOXP3) transcription factor which is crucial for the development, maturation, and maintenance of CD4+ regulatory T (T-reg) cells. Various autoimmune phenomena such as enteropathy, endocrinopathies, cytopenias, renal disease, and skin manifestations are characteristic findings in patients affected by IPEX syndrome. Objectives In this systematic review, we focus on both clinical and demographic characteristics of IPEX patients, highlighting possible genotype-phenotype correlations and address prognostic factors for disease outcome. Methods We performed a literature search to systematically investigate the case reports of IPEX which were published before August 7th, 2017. Results A total of 75 articles (195 patients) were identified. All IPEX patients included had FOXP3 mutations which were most frequently located in the forkhead domain (n = 68, 34.9%) followed by the leucine-zipper domain (n = 30, 15.4%) and repressor domain (n = 36, 18.4%). Clinical manifestations were as follows: enteropathy (n = 191, 97.9%), skin manifestations (n = 121, 62.1%), endocrinopathy (n = 104, 53.3%), hematologic abnormalities (n = 75, 38.5%), infections (n = 78, 40.0%), other immune-related complications (n = 43, 22.1%), and renal involvement (n = 32, 16.4%). Enteropathic presentations (P = 0.017), eczema (P = 0.030), autoimmune hemolytic anemia (P = 0.022) and food allergy (P = 0.009) were associated with better survival, while thrombocytopenia (P = 0.034), septic shock (P = 0.045) and mutations affecting the repressor domain (P = 0.021), intron 7 (P = 0.033) or poly A sequence (P = 0.025) were associated with increased risk of death. Immunosuppressive therapy alone was significantly associated with increased cumulative survival compared to patients who received no treatment (P = 0.041). Conclusions We report the most comprehensive summary of demographic and clinical profiles derived from a total of 195 IPEX patients with deleterious mutations in FOXP3. Analysis of our findings provides new insights into genotype/phenotype correlations, and clinical and genetic factors associated with increased risk of death and response to treatment strategies.
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Primary immune deficiency disorders presenting as autoimmune diseases: IPEX and APECED.
Journal of Clinical Immunology, 2008Co-Authors: Dewton Moraes-vasconcelos, Troy R Torgerson, Beatriz Tavares Costa-carvalho, Hans D. OchsAbstract:Background Several primary immune deficiency disorders are associated with autoimmunity and malignancy, suggesting a state of immune dysregulation. The concept of immune dysregulation as a direct cause of autoimmunity in primary immune deficiency disorders (PIDDs) has been strengthened by the recent discovery of distinct clinical entities linked to single-gene defects resulting in multiple autoimmune phenomena including immune dysregulation, Polyendocrinopathy, enteropathy and X-linked (IPEX) syndrome, and autoimmune Polyendocrinopathy, candidiasis and ectodermal dystrophy (APECED) syndrome.
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immune dysregulation Polyendocrinopathy enteropathy x linked inheritance model for autoaggression
Advances in Experimental Medicine and Biology, 2007Co-Authors: Hans D. Ochs, Troy R TorgersonAbstract:Patients with the rare X-linked syndrome, immune dysregulation, Polyendocrinopathy, enteropathy (IPEX) may present early in life with type I diabetes, hyperthyroidism, chronic enteropathy, villous atrophy, dermatitis, autoimmune hemolytic anemia, and antibody- induced neutropenia and thrombocytopenia. Of the reported families with IPEX, most affected boys died before the age of 3 years of malabsorbtion, failure to thrive, infections, or other complications. Characteristic findings at autopsy include lymphocytic infiltrates affecting the lungs, endocrine organs, such as pancreas and thyroid and skin, and increased lymphoid elements in lymph nodes and spleen. Although symptomatic therapy with immunosuppressive drugs provides some beneficial effects, the only curative treatment is hematopoietic stem cell transplantation.
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single cell analysis of normal and foxp3 mutant human t cells foxp3 expression without regulatory t cell development
Proceedings of the National Academy of Sciences of the United States of America, 2006Co-Authors: Marc A Gavin, Paul Deroos, Evan G Houston, Asbjorg Straypedersen, Elizabeth L Ocheltree, William Ho, Troy R Torgerson, Philip D. Greenberg, Hans D. Ochs, Alexander Y RudenskyAbstract:Forkhead winged-helix transcription factor Foxp3 serves as the dedicated mediator of the genetic program governing CD25+CD4+ regulatory T cell (Tr) development and function in mice. In humans, its role in mediating Tr development has been controversial. Furthermore, the fate of Tr precursors in FOXP3 deficiency has yet to be described. Making use of flow cytometric detection of human FOXP3, we have addressed the relationship between FOXP3 expression and human Tr development. Unlike murine Foxp3− T cells, a small subset of human CD4+ and CD8+ T cells transiently up-regulated FOXP3 upon in vitro stimulation. Induced FOXP3, however, did not alter cell-surface phenotype or suppress T helper 1 cytokine expression. Furthermore, only ex vivo FOXP3+ Tr cells persisted after prolonged culture, suggesting that induced FOXP3 did not activate a Tr developmental program in a significant number of cells. FOXP3 flow cytometry was also used to further characterize several patients exhibiting symptoms of immune dysregulation, Polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) with or without FOXP3 mutations. Most patients lacked FOXP3-expressing cells, further solidifying the association between FOXP3 deficiency and immune dysregulation, Polyendocrinopathy, enteropathy, X-linked syndrome. Interestingly, one patient bearing a FOXP3 mutation enabling expression of stable FOXP3mut protein exhibited FOXP3mut-expressing cells among a subset of highly activated CD4+ T cells. This observation raises the possibility that the severe autoimmunity in FOXP3 deficiency can be attributed, in part, to aggressive T helper cells that have developed from Tr precursors.
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successful use of the new immune suppressor sirolimus in ipex immune dysregulation Polyendocrinopathy enteropathy x linked syndrome
The Journal of Pediatrics, 2005Co-Authors: L Bindl, Hans D. Ochs, Olivier Goulet, Lucia Perroni, Troy Torgerson, Nelly Youssef, Frank M. RuemmeleAbstract:IPEX (immune-dysregulation, Polyendocrinopathy, enteropathy, X-linked) syndrome is an autoimmune disorder with an often lethal outcome in spite of immunosuppressive therapy. We report the successful use of sirolimus in 3 patients with IPEX. The efficacy of sirolimus is probably due to its different mode of action compared to calcineurin-dependent agents.
Troy R Torgerson - One of the best experts on this subject based on the ideXlab platform.
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primary immune regulatory disorders for the pediatric hematologist and oncologist a case based review
Pediatric Blood & Cancer, 2019Co-Authors: Shanmuganathan Chandrakasan, Troy R Torgerson, Sharat Chandra, Blachy Davila J Saldana, David BuchbinderAbstract:An array of monogenic immune defects marked by autoimmunity, lymphoproliferation, and hyperinflammation rather than infections have been described. Primary immune regulatory disorders pose a challenge to pediatric hematologists and oncologists. This paper focuses on primary immune regulatory disorders including autoimmune lymphoproliferative syndrome (ALPS) and ALPS-like syndromes, immunodysregulation, Polyendocrinopathy, enteropathy, X-linked (IPEX) and IPEX-like disorders, common variable immunodeficiency (CVID), CVID-like, and late-onset combined immunodeficiency (CID) disorders. Hyperinflammatory disorders and those associated with increased susceptibility to lymphoid malignancies are also discussed. Using a case-based approach, a review of clinical pearls germane to the clinical and laboratory evaluation as well as the treatment of these disorders is provided.
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the immunogenetics of immune dysregulation Polyendocrinopathy enteropathy x linked ipex syndrome
Journal of Medical Genetics, 2012Co-Authors: Eva Dhennezel, Troy R Torgerson, Khalid Bin Dhuban, Ciriaco A. PiccirilloAbstract:Immune dysregulation, Polyendocrinopathy, enteropathy, X linked (IPEX) syndrome is a rare disorder in humans caused by germ-line mutations in the FOXP3 gene, a master transcriptional regulator for the development of CD4 regulatory T (Treg) cells. This T cell subset has global inhibitory functions that maintain immune homeostasis and mediate self-tolerance. Treg developmental deficiency or dysfunction is a hallmark of IPEX. It leads to severe, multi-organ, autoimmune phenomena including enteropathy, chronic dermatitis, endocrinopathy and other organ-specific diseases such as anaemia, thrombocytopenia, hepatitis and nephritis. In this review, the genetic, immunological and clinical characteristics of IPEX syndrome are described, and the impact of heritable mutations on the function of Treg cells highlighted.
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Primary immune deficiency disorders presenting as autoimmune diseases: IPEX and APECED.
Journal of Clinical Immunology, 2008Co-Authors: Dewton Moraes-vasconcelos, Troy R Torgerson, Beatriz Tavares Costa-carvalho, Hans D. OchsAbstract:Background Several primary immune deficiency disorders are associated with autoimmunity and malignancy, suggesting a state of immune dysregulation. The concept of immune dysregulation as a direct cause of autoimmunity in primary immune deficiency disorders (PIDDs) has been strengthened by the recent discovery of distinct clinical entities linked to single-gene defects resulting in multiple autoimmune phenomena including immune dysregulation, Polyendocrinopathy, enteropathy and X-linked (IPEX) syndrome, and autoimmune Polyendocrinopathy, candidiasis and ectodermal dystrophy (APECED) syndrome.
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immune dysregulation Polyendocrinopathy enteropathy x linked inheritance model for autoaggression
Advances in Experimental Medicine and Biology, 2007Co-Authors: Hans D. Ochs, Troy R TorgersonAbstract:Patients with the rare X-linked syndrome, immune dysregulation, Polyendocrinopathy, enteropathy (IPEX) may present early in life with type I diabetes, hyperthyroidism, chronic enteropathy, villous atrophy, dermatitis, autoimmune hemolytic anemia, and antibody- induced neutropenia and thrombocytopenia. Of the reported families with IPEX, most affected boys died before the age of 3 years of malabsorbtion, failure to thrive, infections, or other complications. Characteristic findings at autopsy include lymphocytic infiltrates affecting the lungs, endocrine organs, such as pancreas and thyroid and skin, and increased lymphoid elements in lymph nodes and spleen. Although symptomatic therapy with immunosuppressive drugs provides some beneficial effects, the only curative treatment is hematopoietic stem cell transplantation.
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single cell analysis of normal and foxp3 mutant human t cells foxp3 expression without regulatory t cell development
Proceedings of the National Academy of Sciences of the United States of America, 2006Co-Authors: Marc A Gavin, Paul Deroos, Evan G Houston, Asbjorg Straypedersen, Elizabeth L Ocheltree, William Ho, Troy R Torgerson, Philip D. Greenberg, Hans D. Ochs, Alexander Y RudenskyAbstract:Forkhead winged-helix transcription factor Foxp3 serves as the dedicated mediator of the genetic program governing CD25+CD4+ regulatory T cell (Tr) development and function in mice. In humans, its role in mediating Tr development has been controversial. Furthermore, the fate of Tr precursors in FOXP3 deficiency has yet to be described. Making use of flow cytometric detection of human FOXP3, we have addressed the relationship between FOXP3 expression and human Tr development. Unlike murine Foxp3− T cells, a small subset of human CD4+ and CD8+ T cells transiently up-regulated FOXP3 upon in vitro stimulation. Induced FOXP3, however, did not alter cell-surface phenotype or suppress T helper 1 cytokine expression. Furthermore, only ex vivo FOXP3+ Tr cells persisted after prolonged culture, suggesting that induced FOXP3 did not activate a Tr developmental program in a significant number of cells. FOXP3 flow cytometry was also used to further characterize several patients exhibiting symptoms of immune dysregulation, Polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) with or without FOXP3 mutations. Most patients lacked FOXP3-expressing cells, further solidifying the association between FOXP3 deficiency and immune dysregulation, Polyendocrinopathy, enteropathy, X-linked syndrome. Interestingly, one patient bearing a FOXP3 mutation enabling expression of stable FOXP3mut protein exhibited FOXP3mut-expressing cells among a subset of highly activated CD4+ T cells. This observation raises the possibility that the severe autoimmunity in FOXP3 deficiency can be attributed, in part, to aggressive T helper cells that have developed from Tr precursors.
Antoine P Brezin - One of the best experts on this subject based on the ideXlab platform.
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ocular manifestations of autoimmune Polyendocrinopathy syndrome type 1
Current Opinion in Ophthalmology, 2016Co-Authors: Aude Couturier, Antoine P BrezinAbstract:Purpose of review The ocular manifestations in autoimmune Polyendocrinopathy syndrome type 1 (APS1) are frequent and have a poor prognosis. The phenotype of these APS1-associated ocular features have been recently characterized in molecularly confirmed patients with APS1. Recent findings Keratopathy and retinopathy can be severe manifestations of APS1. Heterogeneous corneal involvement can be observed, ranging from minimal superficial punctate staining to severe stromal scarring with deep corneal neovascularization. This phenotypic heterogeneity, observed even in patients with identical AIRE mutations, is suggestive of a poor genotype-phenotype correlation. Similarly, in patients with retinopathy, peripheral pigmentary changes are noted in all cases, yet with heterogeneous severity, ranging from isolated patchy atrophy of the retinal pigment epithelium to a retinitis pigmentosa-like fundus. Macular atrophy with vision loss is found in most cases. The severity of ophthalmic findings is uncorrelated to that of systemic manifestations. An autoimmune origin with specific autoantibodies directed against corneal and/or retinal autoantigens is the main mechanism believed to be responsible for the ocular manifestations of APS1. Summary Progressive keratopathy and/or retinopathy can lead to severe visual loss and pain in patients with APS1. Although no treatment has shown efficacy regarding the APS1-associated ocular manifestations, ophthalmologic examinations are recommended in these patients.
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keratopathy in autoimmune Polyendocrinopathy syndrome type 1
Cornea, 2015Co-Authors: Aude Couturier, Pascale Saugierveber, Jeanclaude Carel, Jerome Bertherat, Antoine P BrezinAbstract:Purpose To report the spectrum of phenotypes in patients with autoimmune Polyendocrinopathy syndrome type 1 (APS1)-related keratopathy. Methods In this retrospective observational case series, 6 patients followed for APS1 were included. Data collected included family history, age at presentation, and systemic and ophthalmic manifestations. The 14 coding exons of the autoimmune regulator (AIRE) gene were sequenced. Results The age at the onset of keratopathy ranged from 4 to 20 years. The ocular symptoms varied from mild photophobia to severe pain, and visual acuity was from light perception to 20/20 Snellen equivalent. Heterogeneous corneal involvement was observed, ranging from minimal superficial punctate staining to severe stromal scarring with deep corneal neovascularization. The severity of ophthalmic findings was uncorrelated to that of systemic manifestations. The genetic analyses identified 2 novel mutations (c.173C>A in exon 2 and c.892G>T in exon 8) and 4 known mutations (c.62C>T in exon 1, c.415C>T in exon 3, c.1096-1G>A in intron 9, and c.1193delC in exon 10) in the AIRE gene. In patients with identical AIRE mutations, including within a sib-pair, heterogeneous phenotypes were observed. Conclusions Keratopathy can be an early and severe manifestation of APS1, which contributes to the global prognosis of the disease. Its mechanisms remain to be elucidated.
