Редактирование: AIRE

Autoimmune regulator (Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy protein) (APECED protein) [APECED]

==Publications==

{{medline-entry
|title=Immunological senescence and thymic function in transplantation.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/19667967
|abstract=In the field of organ transplantation, the state of thymic function has not been a major concern but data from bone marrow transplantation studies have unravel the persistence of some thymopoiesis in the adult and, more importantly, the possibility of reinducing it. Given the central role of the thymus in tolerance, these facts have stimulated the interest in the biology of the thymus in humans. Contemporarily, basic research has provided new tools, if imperfect, to monitor thymic function, that is, T-cell receptor excision circles, markers for lymphocytes recently emigrated from the thymus and new imaging techniques. The deployment of these new tools is already changing some paradigms and has now established that re-enactment of thymic activity in the course of bone marrow transplantation or in patients with human immunodeficiency virus on highly active anti-retroviral therapy is beneficial and that can be achieved in the adult. Clinical trials using thymopoiesis-stimulating factors are underway. On the other hand, the discovery that the thymus contains a broad representation of self-antigens and that this depends on the expression of the product of the gene [[AIRE]] by the medullary thymic epithelial cells opens the possibility of manipulating central tolerance. Current protocols inducing microchimerism to generate tolerance to solid organ grafts suggest that this could be a feasible therapeutic goal. Therefore, there are many signs indicating that a period of translational research applying the principles of thymic biology and central tolerance to transplantation has already started.
|mesh-terms=* Adult
* Aging
* Autoantigens
* Autoimmunity
* Bone Marrow Transplantation
* HIV Infections
* Hematopoietic Stem Cell Transplantation
* Humans
* Immune Tolerance
* Organ Transplantation
* Receptors, Antigen, T-Cell
* T-Lymphocytes
* Thymus Gland
* Transplantation Immunology

|full-text-url=https://sci-hub.do/10.1097/TP.0b013e3181af653c
}}
{{medline-entry
|title=Determining the cost-effectiveness of preventing cardiovascular disease: are estimates calculated over the duration of a clinical trial adequate?
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/18401465
|abstract=Economic analyses of randomized clinical trials often focus only on the results that are observed during the study. However, for many preventive interventions, associated costs and benefits will accrue over a patient's remaining lifetime. To determine the importance of the chosen time horizon, the cost-effectiveness (C/E) of ramipril therapy was calculated and compared in the Heart Outcomes Prevention Evaluation (HOPE), the Microalbuminuria, Cardiovascular, and Renal Outcomes in HOPE (MICRO-HOPE) and the Acute Infarction Ramipril Efficacy ([[AIRE]]) study versus the entire life expectancy (L/E) of potential patients. The Cardiovascular Disease Life Expectancy model, a validated Markov model, was calibrated to accurately forecast the results of each trial. These results were then extrapolated over the remaining L/E of hypothetical patients 55 to 75 years of age. The predicted change in L/E and associated direct health care costs for Canadians were calculated and discounted 3% annually. In HOPE, the forecasted increased L/E averaged 0.06 years during the five-year study versus 1.3 years over the remaining years of L/E. The associated C/E of ramipril was $15,000 per year of life saved (YOLS) over the study duration and $8,500/YOLS over the remaining lifetime. For hypothetical patients, the C/E of ramipril over 4.5 years ranged from $6,700/YOLS to more than $58,300/YOLS and was lowest among elderly men. When the remaining L/E was considered, the C/E of ramipril was similar for men and women of all ages, ranging from $8,100/YOLS to $10,200/YOLS. The analyses of MICRO-HOPE and [[AIRE]] provided similar results. The estimated efficacy and associated C/E of ramipril in HOPE, MICRO-HOPE and the [[AIRE]] study is extremely sensitive to the selected time horizon. Economic analyses beyond the duration of randomized clinical trials are required to fully evaluate the potential costs and benefits of long-term preventive therapies.
|mesh-terms=* Aged
* Angiotensin-Converting Enzyme Inhibitors
* Canada
* Cardiovascular Diseases
* Cost-Benefit Analysis
* Drug Costs
* Female
* Humans
* Life Expectancy
* Male
* Markov Chains
* Middle Aged
* Outcome Assessment, Health Care
* Ramipril
* Randomized Controlled Trials as Topic
* Value of Life

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2644029
}}
{{medline-entry
|title=Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/16684821
|abstract=Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy is known as a rare hereditary disease with classic triad of mucocutaneous candidiasis, hypoparathyroidism, and adrenocortical failure, two of which, diagnostic dyad, are required for the diagnosis. Evidently many patients suffer unrecognized because the condition is more variable and complex. The objective of the study was to describe the variability of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy for promoting recognition and adequate follow-up of patients. The Finnish series of patients is the largest internationally. The study population was all 91 known Finnish patients. Besides the classical triad, a dozen autoimmune endocrine and other components occurred variably, several of them dangerous. The initial manifestation appeared within the age range of 0.2-18 yr, mucocutaneous candidiasis being part of it in 60% of the patients, hypoparathyroidism in 32%, and adrenocortical failure in 5%. But 23% of the patients had one to six other components before the diagnostic dyad: hepatitis, keratoconjunctivitis, chronic diarrhea, periodic rash with fever. The dyad appeared 0.2-20 yr later. Prevalence of most components increased with age, diabetes mellitus, hypothyroidism, and testicular failure becoming common toward middle age. Tubulointerstitial nephritis occurred in 9% of the patients, apparent mineralocorticoid excess in 9%, asplenia in 19% of adults, and oral or esophageal squamous cell carcinoma in 10% of patients older than 25 yr. Any child or young adult with one of the many disease components should be examined for others and consideration of [[AIRE]] mutation assay.
|mesh-terms=* Adolescent
* Adrenal Cortex Diseases
* Adult
* Aging
* Candidiasis, Chronic Mucocutaneous
* Child
* Child, Preschool
* Chronic Disease
* Diabetes Mellitus
* Diarrhea
* Female
* Finland
* Hepatitis
* Humans
* Hypoparathyroidism
* Hypothyroidism
* Infant
* Keratoconjunctivitis
* Male
* Middle Aged
* Polyendocrinopathies, Autoimmune
* Skin Diseases
* Testicular Diseases

|full-text-url=https://sci-hub.do/10.1210/jc.2005-2611
}}
{{medline-entry
|title=Projection of an immunological self shadow within the thymus by the aire protein.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/12376594
|abstract=Humans expressing a defective form of the transcription factor [[AIRE]] (autoimmune regulator) develop multiorgan autoimmune disease. We used aire- deficient mice to test the hypothesis that this transcription factor regulates autoimmunity by promoting the ectopic expression of peripheral tissue- restricted antigens in medullary epithelial cells of the thymus. This hypothesis proved correct. The mutant animals exhibited a defined profile of autoimmune diseases that depended on the absence of aire in stromal cells of the thymus. Aire-deficient thymic medullary epithelial cells showed a specific reduction in ectopic transcription of genes encoding peripheral antigens. These findings highlight the importance of thymically imposed "central" tolerance in controlling autoimmunity.
|mesh-terms=* Aging
* Animals
* Autoantibodies
* Autoantigens
* Autoimmune Diseases
* Autoimmunity
* Epithelial Cells
* Female
* Gene Expression Profiling
* Gene Expression Regulation
* Gene Targeting
* Humans
* Lymphocytes
* Male
* Mice
* Mice, Inbred C57BL
* Mice, Knockout
* Polyendocrinopathies, Autoimmune
* Radiation Chimera
* Reverse Transcriptase Polymerase Chain Reaction
* Self Tolerance
* Stromal Cells
* T-Lymphocytes
* Thymus Gland
* Transcription Factors

|full-text-url=https://sci-hub.do/10.1126/science.1075958
}}