The Role of Interferon-γ in Autoimmune Polyendocrine Syndrome Type 1.

BACKGROUND: Autoimmune polyendocrine syndrome type 1 (APS-1) is a life-threatening, autosomal recessive syndrome caused by autoimmune regulator (AIRE) deficiency. In APS-1, self-reactive T cells escape thymic negative selection, infiltrate organs, and drive autoimmune injury. The effector mechanisms governing T-cell-mediated damage in APS-1 remain poorly understood. METHODS: We examined whether APS-1 could be classified as a disease mediated by interferon-γ. We first assessed patients with APS-1 who were participating in a prospective natural history study and evaluated mRNA and protein expression in blood and tissues. We then examined the pathogenic role of interferon-γ using Aire-/-Ifng-/- mice and Aire-/- mice treated with the Janus kinase (JAK) inhibitor ruxolitinib. On the basis of our findings, we used ruxolitinib to treat five patients with APS-1 and assessed clinical, immunologic, histologic, transcriptional, and autoantibody responses. RESULTS: Patients with APS-1 had enhanced interferon-γ responses in blood and in all examined autoimmunity-affected tissues. Aire-/- mice had selectively increased interferon-γ production by T cells and enhanced interferon-γ, phosphorylated signal transducer and activator of transcription 1 (pSTAT1), and CXCL9 signals in multiple organs. Ifng ablation or ruxolitinib-induced JAK-STAT blockade in Aire-/- mice normalized interferon-γ responses and averted T-cell infiltration and damage in organs. Ruxolitinib treatment of five patients with APS-1 led to decreased levels of T-cell-derived interferon-γ, normalized interferon-γ and CXCL9 levels, and remission of alopecia, oral candidiasis, nail dystrophy, gastritis, enteritis, arthritis, Sjögren's-like syndrome, urticaria, and thyroiditis. No serious adverse effects from ruxolitinib were identified in these patients. CONCLUSIONS: Our findings indicate that APS-1, which is caused by AIRE deficiency, is characterized by excessive, multiorgan interferon-γ-mediated responses. JAK inhibition with ruxolitinib in five patients showed promising results. (Funded by the National Institute of Allergy and Infectious Diseases and others.).

Dysregulated germinal center reaction with expanded T follicular helper cells in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy lymph nodes.

BACKGROUND: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED, also called APS-1) is an inborn error of immunity with clear signs of B-cell autoimmunity such as neutralizing anti-IFN antibodies. In APECED, mutations in the AIRE gene impair thymic negative selection of T cells. The resulting T-cell alterations may then cause dysregulation of B-cell responses. However, no analysis of interactions of T and B cells in the germinal centers (GCs) in patients' secondary lymphatic tissues has been reported. OBJECTIVE: This study examined the relationship between B cells and follicular T helper cells (TfH) in peripheral blood and lymph node (LN) GCs in patients with APECED. METHODS: Immunophenotyping of peripheral blood B cells and TfH was performed for 24 patients with APECED. Highly multiplexed fluorescent immunohistochemical staining was performed on 7 LN biopsy samples from the patients to study spatial interactions of lymphocytes in the GCs at the single-cell level. RESULTS: The patients' peripheral B-cell phenotype revealed skewing toward a mature B-cell phenotype with marked loss of transitional and naive B cells. The frequency of circulating TfH cells was diminished in the patients, while in the LNs the TfH population was expanded. In LNs the overall frequency of Treg cells and interactions of Treg cells with nonfollicular T cells were reduced, suggesting that aberrant Treg cell function might fail to restrain TfH differentiation. CONCLUSIONS: GC reactions are disrupted in APECED as a result of defective T-cell control.

Increased type 1 inflammation in gynecologic cervicovaginal samples in patients with APS-1.

BACKGROUND: Inborn errors of immunity offer important insights into mucosal immunity. In autoimmune polyendocrine syndrome type-1 (APS-1), chronic mucocutaneous candidiasis has been ascribed to neutralizing IL-17 autoantibodies. Recent evidence implicates excessive T-cell IFN-γ secretion and ensuing epithelial barrier disruption in predisposition to candidiasis, but these results remain to be replicated. Whether IL-17 paucity, increased type I inflammation, or their combination underlies susceptibility to chronic mucocutaneus candidiasis in APS-1 is debated. OBJECTIVE: Our aim was to characterize the immunologic features in the cervicovaginal mucosa of females with APS-1. METHODS: Vaginal fluid was collected with a flocked swab from 17 females with APS-1 and 18 controls, and cytokine composition was analyzed using Luminex (Luminex Corporation, Austin, Tex). Cervical cell samples were obtained with a cervix brush from 6 patients and 6 healthy controls and subjected to transcriptome analysis. RESULTS: The vaginal fluid samples from patients with APS-1 had IFN-γ concentrations comparable to those of the controls (2.6 vs 2.4 pg/mL) but high concentrations of the TH1 chemokines CXCL9 and CXCL10 (1094 vs 110 pg/mL [P < .001] and 4033 vs 273 pg/mL [P = .001], respectively), whereas the IL-17 levels in the samples from the 2 groups were comparable (28 vs 8.8 pg/mL). RNA sequencing of the cervical cells revealed upregulation of pathways related to mucosal inflammation and cell death in the patients with APS-1. CONCLUSION: Excessive TH1 cell response appears to underlie disruption of the mucosal immune responses in the genital tract of patients with APS-1 and may contribute to susceptibility to candidiasis in the genital tract as well.

Neurological Diseases and Prevalence of Antineuronal Antibodies in Patients with Autoimmune Polyendocrine Syndrome Type 1 - A National Cohort Study.

Autoimmune polyendocrine syndrome type 1 (APS-1) is a rare monogenic disease caused by mutations in the autoimmune regulator gene. Although the disease-associated autoantibodies mostly target endocrine organs, autoantibodies from patients with APS-1 bind also to rat brain structures. The patients often have GAD65-antibodies, that can cause autoimmune encephalitis. However, neurological manifestations of APS-1 have not been systematically explored. We conducted a retrospective chart review on 44 Finnish patients with APS-1 (median age 38 years, 61% females) and collected all their neurological diagnoses. To assess the prevalence of serum antineuronal antibodies in APS-1, serum samples of 24 patients (median age 36 years, 63% females) were analyzed using a fixed cell-based assay. Of the 44 APS-1 patients, 10 (23%) had also received a diagnosis of a neurological disease. Of these neurological comorbidities, migraine (n = 7; 16%), central nervous system infections (n = 3; 7%), and epilepsy (n = 2; 5%) were the most prevalent. Other diagnoses recorded for single patients were axonal sensorimotor polyneuropathy, essential tremor, idiopathic intracranial hypertension, ischemic stroke, and trigeminal neuralgia. Serum antineuronal antibodies were detected in 42% of patients tested (10/24, 50% females, median age 42 years), GAD65 antibodies being the most common finding. Antibodies against glycine and aquaporin 4 were found in low titers. In four patients, relatively high titers of GAD65 antibodies without coexisting type 1 diabetes were found, but none presented with GAD65-encephalitis. Our study suggests an association between APS-1 and neurological disorders, the mechanisms of which are to be further investigated.

Clinical manifestations, diagnosis and long-term prognosis of adult autoimmune enteropathy: Experience from Peking Union Medical College Hospital.

BACKGROUND: Autoimmune enteropathy (AIE) is a rare disease whose diagnosis and long-term prognosis remain challenging, especially for adult AIE patients. AIM: To improve overall understanding of this disease's diagnosis and prognosis. METHODS: We retrospectively analyzed the clinical, endoscopic and histopathological characteristics and prognoses of 16 adult AIE patients in our tertiary medical center between 2011 and 2023, whose diagnosis was based on the 2007 diagnostic criteria. RESULTS: Diarrhea in AIE patients was characterized by secretory diarrhea. The common endoscopic manifestations were edema, villous blunting and mucosal hyperemia in the duodenum and ileum. Villous blunting (100%), deep crypt lymphocytic infiltration (67%), apoptotic bodies (50%), and mild intraepithelial lymphocytosis (69%) were observed in the duodenal biopsies. Moreover, there were other remarkable abnormalities, including reduced or absent goblet cells (duodenum 94%, ileum 62%), reduced or absent Paneth cells (duodenum 94%, ileum 69%) and neutrophil infiltration (duodenum 100%, ileum 69%). Our patients also fulfilled the 2018 diagnostic criteria but did not match the 2022 diagnostic criteria due to undetectable anti-enterocyte antibodies. All patients received glucocorticoid therapy as the initial medication, of which 14/16 patients achieved a clinical response in 5 (IQR: 3-20) days. Immunosuppressants were administered to 9 patients with indications of steroid dependence (6/9), steroid refractory status (2/9), or intensified maintenance medication (1/9). During the median of 20.5 months of follow-up, 2 patients died from multiple organ failure, and 1 was diagnosed with non-Hodgkin's lymphoma. The cumulative relapse-free survival rates were 62.5%, 55.6% and 37.0% at 6 months, 12 months and 48 months, respectively. CONCLUSION: Certain histopathological findings, including a decrease or disappearance of goblet and Paneth cells in intestinal biopsies, might be potential diagnostic criteria for adult AIE. The long-term prognosis is still unsatisfactory despite corticosteroid and immunosuppressant medications, which highlights the need for early diagnosis and novel medications.

Enfermedades autoinmunitarias asociadas a diabetes mellitus tipo 1A / Autoimmune diseases in type 1A diabetes mellitus

Type 1A diabetes (DM1A) is an autoimmune disease that comprises 10% of patients with diabetes mellitus. Its frequency is gradually increasing in countries like Mexico. Patients with DM1A commonly have hypothyroidism, Addison disease, celiac disease and less common diseases such as polyglandular syndrome. These diseases are related to susceptibility genes such as HLA, CTLA-4 and PTPN22, which induce central and peripheral immunologic tolerance. This review article emphasizes the importance of searching other autoimmune diseases in patients with DM1A, to improve their prognosis and quality of life.

Rastreio de síndrome poliglandular autoimune em uma população de pacientes com diabetes melito tipo 1 / Screening for autoimmune polyglandular syndrome in a cohort of patients with type 1 diabetes mellitus

OBJETIVO: Caracterizar uma população de pacientes com diabetes melito tipo 1 (DMT1) relativamente à presença de outras entidades autoimunes que permitam estabelecer o diagnóstico de síndrome poliglandular autoimune (SPGA). SUJEITOS E MÉTODOS: Incluímos 151 pacientes com DMT1. Analisamos os seguintes parâmetros clínicos: gênero, idade atual, duração da doença, antecedentes pessoais de patologia autoimune e antecedentes familiares de diabetes melito. Submetemos cada doente a um estudo laboratorial com o objetivo de detectar a presença de marcadores imunológicos para a tireoidite, insuficiência adrenocortical, gastrite e doença celíaca, e eventual disfunção associada. RESULTADOS: Coorte com 51,7% homens, idade média atual de 33,4 ± 13 anos e duração da doença de 14,4 ± 9,6 anos. Antecedentes pessoais de autoimunidade presentes em 2% da amostra e história familiar de diabetes melito em 31,1%. A frequência de marcadores imunológicos foi de 24% para a tireoidite, 9,4% para a insuficiência adrenocortical, 17,2% para a gastrite e 2% para a doença celíaca. Foi diagnosticada SPGA em 25,2% dos pacientes. O risco de SPGA e tireoidite autoimune foi superior em mulheres. A duração da doença correlacionou-se diretamente com a presença de autoanticorpos gástricos e inversamente com a positividade dos anticorpos anti-ilhota, antiglutamato descarboxilase e antitirosina fosfatase. Constatou-se a existência de uma associação entre os marcadores imunológicos da tireoidite e gastrite, bem como entre a doença celíaca e insuficiência adrenocortical. CONCLUSÃO: Atendendo à frequência e ao prognóstico inerente à SPGA, a necessidade de realizar rastreio em pacientes com DMT1 é enfatizada. O diagnóstico atempado de outras doenças autoimunes permitirá individualizar o tratamento e seguimento do doente.

OBJECTIVE: To characterize a cohort of patients with type 1 diabetes mellitus (T1DM) on the presence of other autoimmune disorders that could establish the diagnosis of autoimmune polyglandular syndrome (APS). SUBJECTS AND METHODS: We included 151 patients with T1DM. The following clinical parameters were analyzed: gender, current age, disease duration, previous history of autoimmune disorders, and familial history for diabetes mellitus. Each patient was analyzed to detect autoimmune markers of thyroiditis, adrenocortical insufficiency, gastritis, and celiac disease, as well as possible associated dysfunctions. RESULTS: A cohort with 51.7% males, average current age of 33.4 ± 13 years and disease duration of 14.4 ± 9.6 years was analyzed. Previous history of autoimmunity was found in 2%, and familial history for diabetes mellitus in 31.1% of the cohort. Frequency of autoimmune markers was 24% for thyroiditis, 9.4% for adrenocortical insufficiency, 17.2% for gastritis, and 2% for celiac disease. APS was diagnosed on 25.2% of the patients. APS and autoimmune thyroiditis risk was higher in females. Disease duration correlated directly with gastric autoantibodies, and inversely with positive islet cell, glutamic acid decarboxylase, and tyrosine phosphatase antibodies. We noticed a correlation between autoimmune markers for thyroiditis and gastritis, as well as between celiac disease and adrenocortical insufficiency. CONCLUSION: Considering APS prevalence and prognosis, the need for APS screening in patients with T1DM is emphasized. Early diagnosis of other autoimmune disorders will enable us to adjust each patient treatment and follow-up.

Autoimmune polyendocrine syndrome type 1: case report and review of literature / Síndrome poliglandular autoimune tipo 1: descrição de caso e revisão da literatura

Autoimmune polyendocrine syndrome type 1 (APECED) is a rare autosomal recessive disorder characterized by autoimmune multiorgan attack. The disease is caused by mutations in the autoimmune regulator gene (AIRE), resulting in defective AIRE protein, which is essential for selftolerance. Clinical manifestations are widely variable. Although the classic triad is composed by mucocutaneous candidiasis, hypoparathyroidism and adrenal failure, many other components may develop. Treatment is based on supplementation of the various deficiencies, and patients require regular follow-up throughout their lifespan. This article describes the case of a patient with the disease, and reviews literature data on the epidemiology, clinical course, immunogenetic aspects, diagnosis and treatment of the syndrome.

Síndrome poliglandular autoimune tipo 1 é uma rara desordem autossômica recessiva caracterizada por ataque autoimune a diversos órgãos. A doença é causada por mutações no gene AIRE (autoimmune regulator), resultando em uma proteína AIRE defeituosa, proteína esta essencial para a manutenção da autotolerância. As manifestações clínicas são extremamente variáveis. A tríade clássica é composta por candidíase mucocutânea crônica, hipoparatiroidismo e insuficiência adrenal, porém diversos outros componentes podem estar presentes. A base do tratamento é a reposição das diversas deficiências, e os pacientes devem ser acompanhados por toda a vida. Este artigo descreve o caso de uma paciente com a síndrome e apresenta uma revisão sobre a epidemiologia, quadro clínico, aspectos imunogenéticos, diagnóstico e tratamento da desordem, de acordo com a literatura publicada.

Síndrome Poliglandular Autoinmune Tipo II: Posible Asociación con HLA DRB1*-DQB1* / Possible association of Type II Autoimmune Polyendrocrine Syndrome with HLA DRB1*-DQB1*

Los síndromes poliendocrinos autoinmunes (APS) asocian enfermedades endocrinas autoinmunes con otros desórdenes autoinmunes no endocrinos. El APS tipo II se caracteriza por compromiso primario suprarrenal, tiroideo y/o DM tipo I. Presentamos un paciente masculino de 46 años que fue internado por astenia, adinamia, hiporexia, severa disminución de peso, mareos y vómitos. Antecedente de obesidad y diabetes diagnosticada 3 años antes. Presentaba hipotensión arterial, hiperpigmentación de mucosas y pliegues, anemia, hiponatremia e hipoglucemias frecuentes a pesar de la disminución de la dosis de insulina. Se diagnosticó insuficiencia suprarrenal, concomitantemente con hipotiroidismo y diabetes tipo 1, todas de origen autoinmune, iniciándose reemplazo hormonal. Se encontró una posible asociación del HLA DRB1*-DQB1* en los estudios genéticos. Conclusiones: Nuestro paciente presenta el HLA DQB1*0302 descripto en el APSII, pero el HLA DRB1 *08 encontrado no está descripto en este síndrome ni en ningún otro desorden autoinmune. En pacientes con Diabetes tipo 1 que disminuyan el requerimiento insulínico, habría que descartar insuficiencia suprarrenal, un componente del APS II, como factor etiológico, a pesar de su baja prevalencia.

Autoimmune polyendocrine syndromes (APS) are the association of autoimmune endocrine diseases with other non-endocrine autoimmune disorders. Type II APS is defined by occurrence of Addison´s disease with thyroid autoimmune disease and/or type 1 diabetes mellitus. We present a 46-year-old male patient who was hospitalized because of asthenia, adynamia, hyporexia, severe loss of weight, dizziness and vomiting. Diabetes mellitus had been diagnosed 3 years earlier when he was obese. He presented arterial hypotension, anemia, darkening of the skin and oral mucosa, hyponatremia and frequent hypoglycemia although his insulin dose was decreased. Adrenal insufficiency was diagnosed together with hypothyroidism and type 1 diabetes, all of them of autoimmune origin. Hormonal replacement treatment was initiated. Genetic studies were performed and a new polymorphism was found. Conclusions: HLA DRB1 *08 found in our patient has not been described in APS II or in any other autoimmune disorders. He also has HLA DQB1*0302 described in previous reports related to APS II. In type 1 diabetic patients whose insulin requirement decreases, it would be advisable to rule out adrenal insufficiency, a component of APS II, as an etiologic factor in spite of its low prevalence. In diabetic obese patients (mainly young) who lose weight without a defined cause, type 1 diabetes mellitus should be excluded.

Diabetes melito tipo 1 no contexto das poliendocrinopatias auto-imunes: [revisão] / Type 1 diabetes and autoimmune polyendocrine syndromes: [review]

Três entidades clínicas distintas, causadas por desarranjos genéticos, estão associadas a múltiplas desordens auto-imunes: síndrome linfoproliferativa auto-imune, poliendocrinopatias auto-imunes (APSs) e desregulação imune, poliendocrinopatia, enteropatia ligada ao X (IPEX). O diabetes melito auto-imune ou tipo 1 (DM1) pode estar presente nas APSs e na IPEX. A APS-1 caracteriza-se pela associação de candidíase crônica, hipoparatireoidismo e insuficiência adrenal auto-imune ou idiopática (doença de Addison), no entanto, o diabetes melito tipo 1 pode estar presente em até 12 por cento dos casos. A APS-2 inclui a doença de Addison (sempre presente), a doença tireoidiana auto-imune e o diabetes melito tipo 1, enquanto na APS-3 a doença tireoidiana se associa a outra doença imunológica, excluindo a insuficiência adrenal e o hipoparatireoidismo, e a APS-4 é composta por combinações diferentes das descritas anteriormente. Já a IPEX caracteriza-se por alteração rara da regulação auto-imune que resulta doenças auto-imunes de início precoce, envolvendo pâncreas, tireóide, intestino com diarréia secretora grave, eczema e anemia. O diagnóstico e o tratamento das doenças componentes das poliendocrinopatias e da IPEX são semelhantes ao da patologia na forma isolada.

Type 1 diabetes (T1D) is associated with autoimmune thyroid disease (AIT), celiac disease (CD), Addison's disease (AD), and other autoimmune diseases. These diseases can occur simultaneously in defined syndromes with distinct pathophysiology and characteristics: autoimmune polyendocrine syndromes (APSs) and the immunodysregulation polyendocrinopathy enteropathy X-linked syndrome (IPEX). APSs were initially defined as a multiple endocrine gland insufficiency associated to an autoimmune disease in a patient. APS-1 is characterized by the evidence of chronic candidiasis, chronic hypoparathyroidism, AD and T1D could be present as part of this syndrome. The combination of autoimmune adrenal insufficiency with AIT and/or type 1 autoimmune diabetes mellitus defines APS-2. AIT associated to other autoimmune diseases (excluding AD and/or hypoparathyroidism) are the main characteristics of APS-3. Different clinical combinations of autoimmune diseases which were not included in the previous groups are the characteristics of APS-4. IPEX is a recessive disorder characterized by the neonatal onset of T1D, infections, enteropathy, thrombocytopenia and anemia, as well as endocrinopathy, eczema and cachexia. These disorders are not common, but their consequences can be life threatening when the diagnosis is overlooked, and the treatment is the same prescribed for isolated disease presentation.

Heterogeneidade do diabetes melito tipo 1 / Heterogeneity of type 1 diabetes mellitus

O diabetes melito tipo 1 (DM1) caracteriza-se pela deficiência de insulina por causa da destruição das células-beta pancreáticas. O DM1 atualmente é classificado em dois subtipos: um auto-imune (DM1A) e outro não auto-imune (DM1B). O DM1A poligênico (isolado ou associado a outras doenças auto-imunes) é a forma mais prevalente. O DM1A pode fazer parte de síndromes raras em virtude de alterações monogênicas [gene regulador da auto-imunidade (AIRE)] e mutações no gene FOX-p3. O DM1B corresponde de 4 por cento a 7 por cento do DM1 e pode incluir formas não clássicas, como o diabetes fulminante e o DATC. Jovens com DM1A e sinais de resistência à insulina associados têm sido denominados de diabetes duplo (DD), tipo 1 e tipo 2. Nessa revisão são discutidas as patofisiologias e as características clínicas das formas raras de DM1A, o DM1B, as formas atípicas de DM1 não auto-imune e as inter-relações entre a inflamação subclínica da obesidade e o processo auto-imune do DM1A no DD. Em resumo, apresentamos o conceito de heterogeneidade do DM1.

Type 1 diabetes (T1D) comprises all forms of autoimmune-mediated and idiopathic beta-cell destruction leading to absolute insulin deficiency. The etiological heterogeneity of T1D has been recognized for the last decades, but it has been divided into only two subtypes so far: autoimmune (T1D)A and non-autoimmune (T1D)B mediated. Polygenic T1DA (isolated or associated to other autoimmune diseases) is the most prevalent type of T1D. T1DA might be part of rare monogenic syndromes related to mutations in the autoimmune regulator gene (AIRE) and FOXp3. Non-autoimmune forms of T1D correspond to approximately 4 to 7 percent of newly diagnosed T1D and include T1DB, as well as other types of atypical diabetes, for example fulminant type 1 diabetes and adult ketosis-prone diabetes. A new expression of diabetes in young with insulin resistance and obesity, along with the presence of pancreatic autoimmunity markers, namely auto-antibodies to islet cell antigens, is called double diabetes (DD), T1DA plus type 2 diabetes. Evidence has been collected concerning the potential effect of obesity-linked cytokines in amplifying the autoimmune response in DD. Therefore all these issues are presented and discussed in this review as the concept of heterogeneity of Type 1 Diabetes.

Anticuerpos anti 21 hidroxilasa séricos en pacientes con anticuerpos antifracción microsomal: síndrome poliendocrino autoinmune / Seric 21- hydroxilase antibodies in patients with anti-microsomal fraction antibodies: autoimmune polyendocrine syndrome

El síndrome poliendocrino autoinmune (SPA) es la asociación de enfermedades endocrinas autoinmunes con otros desórdenes autoinmunes no endocrinos. Los tipos 1, 2 y 4 presentan adrenalitis autoinmune, esto indica la presencia de autoanticuerpos, y su marcador serológico específico es el anti 21 hidroxilasa (a21-OH). El SPA tipo 2 es la asociación de adrenalitis, enfermedad tiroidea y/o diabetes mellitus inducidas por autoanticuerpos. Como componentes menores, pueden estar asociados entre otros, vitiligo, alopecia y miastenia. Nuestros objetivos fueron: establecer la prevalencia de a21-OH séricos en pacientes con anticuerpos anti fracción microsomal (AFM) positivos, enfermedad tiroidea autoinmune y/o afecciones endocrinas y no endocrinas autoinmunes; diagnosticar formas incompletas de SPA y estudiar individuos con probable riesgo de progresión a un SPA completo. Estudiamos 72 pacientes AFM positivos y 60 sujetos tomados como grupo control, AFM negativos. Hallamos a21-OH elevados en dos pacientes: A= 47 U/ml, hipotiroidismo autoinmune y miastenia; y B= 8.75 U/ml, hipotiroidismo autoinmune y vitiligo; ambos con ausencia de insuficiencia adrenal. La prevalencia de a21-OH encontrada fue del 2.8%. Las pacientes A y B corresponden a un SPA tipo 2 incompleto y latente en relación al componente adrenal. Considerando a los a21-OH marcadores de enfermedad autoinmune latente, el eventual riesgo de evolución hacia la afección clínica sugiere la necesidad de estrechos controles clínicos y bioquímicos periódicos.

Autoimmune polyendocrine syndrome (APS) is the association of autoimmune endocrine diseases, with other autoimmune nonendocrine disorders. APS types 1, 2 and 4 include autoimmune adrenalitis; this suggests the presence of autoantibodies. A specific serological marker for these is the anti 21- hydroxilase autoantibody (a21-OH). APS type 2 is the association of autoimmune adrenalitis, to autoimmune thyroid disease and/or diabetes mellitus, all these are induced by autoantibodies. Alopecia, vitiligo, myasthenia and other manifestations can be minor components. We sought to establish the prevalence of seric a21-OH in patients with positive anti-microsomal fraction autoantibodies, autoimmune thyroid disease and/or non-endocrine autoimmune diseases. We also aimed to diagnose incomplete forms of APS and to follow up patients at risk of progression to complete forms of APS. A population of 72 patients and another of 60 controls with negative anti-microsomal fraction autoantibodies were studied. Elevated seric a21-OH were found in two patients. Patient A with 47 U/ml had autoimmune hypothyroidism and myasthenia; and patient B with 8.75 U/ml had autoimmune hypothyrodism and vitiligo; they both lacked adrenal insufficiency. Seric a21-OH had a prevalence of 2.8%. Regarding the adrenal component, patients A and B had an incomplete and latent APS type 2. Considering a21-OH as markers of latent endocrine autoimmune diseases and taking into account the eventual risk of developing clinical manifestations, periodic biochemical and clinical follow-ups are recommended.