Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 134
Filtrar
Filtros adicionais











País/Região como assunto
Intervalo de ano
2.
Endocr Connect ; 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30530876

RESUMO

Immunoassays of steroid hormones are still used in the diagnosis and monitoring of patients with congenital adrenal hyperplasia. However, cross-reactivity between steroids can give rise to falsely elevated steroid levels. Here we compare the use of immunoassays and liquid chromatography-tandem mass spectrometry (LC-MS/MS) in the monitoring of patients with classic 21-hydroxylase deficiency (21OHD). Steroid profiles in different mutation groups (genotypes) were also compared. Fifty-five patients with classic 21OHD (38 women) were studied. Blood samples were collected in the morning after an overnight medication fast. LC-MS/MS and immunoassays were employed to assay 17-hydroxyprogesterone (17OHP), testosterone and androstenedione. In addition, 21-deoxycortisol (21DF), 11-deoxycortisol (11DF), corticosterone, deoxycorticosterone, cortisone and cortisol were analyzed by LC-MS/MS. Testosterone, androstenedione and 17OHP levels were consistently lower (by about 30-50%) when measured by LC-MS/MS compared with immunoassays, with exception of testosterone in men. There was a significant correlation between 21DF and 17OHP (r=0.87, p<0.001), but three patients had undetectable 21DF. Subjects with no enzyme activity had significantly lower mean 11DF concentrations than subjects with residual activity. The use of LC-MS/MS gives a more specific view of adrenal steroid levels in 21OHD compared with immunoassays, which seem to considerably overestimate the levels of 17OHP and androstenedione. Falsely elevated levels of 17OHP and androstenedione could lead to overtreatment with glucocorticoids.

3.
Front Immunol ; 9: 2468, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30410491

RESUMO

Background: Mutations in RMRP, encoding a non-coding RNA molecule, underlie cartilage-hair hypoplasia (CHH), a syndromic immunodeficiency with multiple pathogenetic mechanisms and variable phenotype. Allergy and asthma have been reported in the CHH population and some patients suffer from autoimmune (AI) diseases. Objective: We explored AI and allergic manifestations in a large cohort of Finnish patients with CHH and correlated clinical features with laboratory parameters and autoantibodies. Methods: We collected clinical and laboratory data from patient interviews and hospital records. Serum samples were tested for a range of autoantibodies including celiac, anti-cytokine, and anti-21-hydroxylase antibodies. Nasal cytology samples were analyzed with microscopy. Results: The study cohort included 104 patients with genetically confirmed CHH; their median age was 39.2 years (range 0.6-73.6). Clinical autoimmunity was common (11/104, 10.6%) and included conditions previously undescribed in subjects with CHH (narcolepsy, psoriasis, idiopathic thrombocytopenic purpura, and multifocal motor axonal neuropathy). Patients with autoimmunity more often had recurrent pneumonia, sepsis, high immunoglobulin (Ig) E and/or undetectable IgA levels. The mortality rates were higher in subjects with AI diseases ( χ ( 2 ) 2 = 14.056, p = 0.0002). Several patients demonstrated serum autoantibody positivity without compatible symptoms. We confirmed the high prevalence of asthma (23%) and allergic rhinoconjunctivitis (39%). Gastrointestinal complaints, mostly persistent diarrhea, were also frequently reported (32/104, 31%). Despite the history of allergic rhinitis, no eosinophils were observed in nasal cytology in five tested patients. Conclusions: AI diseases are common in Finnish patients with CHH and are associated with higher mortality, recurrent pneumonia, sepsis, high IgE and/or undetectable IgA levels. Serum positivity for some autoantibodies was not associated with clinical autoimmunity. The high prevalence of persistent diarrhea, asthma, and symptoms of inflammation of nasal mucosa may indicate common pathways of immune dysregulation.

4.
J Intern Med ; 2018 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-30485554

RESUMO

BACKGROUND: Patients with hypoparathyroidism are at risk of both hypocalcemic and hypercalcemic crisis. Patients report that health professionals do not always respond adequately in an acute situation. The extent and handling of severe hypo- and hypercalcemia in hypoparathyroidism is unknown. AIMS: To outline the need for a medical emergency card for primary hypoparathyroidism. METHOD: Postal survey among Norwegian and Swedish patients with chronic hypoparathyroidism of all causes. Altogether 455 invitations were sent (333 from Norway and 122 from Sweden). RESULTS: 336 of 455 (74%) patients responded (253 from Norway and 83 from Sweden). The majority was women (79%) and the main cause post-surgical hypoparathyroidism (66%). Overall 44% and 16% had been hospitalized at least once for hypo- or hypercalcemia, respectively. Eighty-seven percent felt that an emergency card would be highly needed or useful. Among those hospitalized for hypocalcemia, 95% felt a card was needed compared to 90% among those hospitalized for hypercalcemia. Five percent believed that a card would not be useful. CONCLUSIONS: The majority answered that an acute card is highly needed or useful. Hospitalization for acute hypocalcemia was more common (44%) than for acute hypercalcemia (16%). As a result of this survey an emergency card will be distributed in three European countries to test its utility. This article is protected by copyright. All rights reserved.

5.
J Diabetes ; 2018 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-30367557

RESUMO

BACKGROUND: Peripheral arterial disease (PAD) and diabetes mellitus (DM) represent major public health challenges and are tightly associated. To facilitate early diagnosis, HbA1c has been implemented as the preferred diagnostic tool for the diagnosis of type 2 DM. In this study, we compared and evaluated HbA1c, fasting plasma glucose (FPG), and 2-hour post-load glucose values to determine which test best predicted mortality in patients with PAD. METHODS: In all, 273 PAD patients with unknown glycemic status admitted to Haukeland University Hospital for elective surgery between October 2006 and September 2007 were included in the study. All 273 patients underwent a standard oral glucose tolerance test (OGTT) in addition to determination of HbA1c; patients were then grouped into those with DM, intermediate hyperglycemia, and normoglycemia according to World Health Organization and International Expert Committee criteria. RESULTS: All-cause mortality was 40% over a 9-year follow-up period. After adjusting for age, sex, and relevant medication, HbA1c was a predictor for mortality (hazard ratio [HR] 1.54; 95% confidence interval [CI] 1.03-2.32]; P = 0.04). The association did not achieve statistical significance in a fully adjusted Cox regression model, although the effect estimation of HbA1c on all-cause mortality remained largely unchanged (HR 1.39; 95% CI 0.92-2.09; P = 0.13). The OGTT was not a predictor of long-term mortality. CONCLUSIONS: The results indicate that HbA1c is a useful marker in the preoperative screening of patients of unknown glycemic status at the time of admission for vascular surgery, and may identify people at high risk of long-term mortality following surgical treatment for PAD.

6.
Artigo em Inglês | MEDLINE | ID: mdl-30177913

RESUMO

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.

7.
J Clin Endocrinol Metab ; 103(12): 4553-4560, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30137397

RESUMO

Context: Autonomous cortisol secretion (ACS) can be unilateral or bilateral irrespective of the presence of an adrenal tumor. A reliable method to distinguish between unilateral and bilateral ACS is lacking. Objective: Evaluate the use of adrenal venous sampling (AVS) to distinguish between unilateral and bilateral ACS. Design and Methods: This was a prospective study of AVS in patients with adrenal tumors who received a diagnosis of ACS or adrenal Cushing syndrome (CS). Unilateral secretion was defined as >2.3-fold difference in cortisol levels between the two adrenal veins. Metanephrine levels were used to ascertain correct catheter position. Results were correlated with findings on CT and iodine-131-cholesterol scintigraphy. Results: Thirty-nine patients underwent AVS; there were no complications. The procedure was inconclusive in six patients and repeated with success in one, giving a success rate of 85%, and leaving 34 procedures for evaluation (adrenal CS, n = 2; ACS, n = 32). Of 14 patients with bilateral tumors, 10 had bilateral and 4 had unilateral overproduction. Of 20 patients with unilateral tumors, 11 had lateralization to the side of the tumor and the remaining had bilateral secretion. Cholesterol scintigraphy findings were concordant with those of AVS in 13 of 18 cases (72%) and discordant in 5 (28%). Conclusion: Laterality of ACS does not always correspond to findings on CT images. AVS is a safe and valuable tool for differentiation between unilateral and bilateral cortisol secretion and should be considered when operative treatment of ACS is a possibility.

9.
Front Horm Res ; 49: 104-113, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29894991

RESUMO

Pharmacological glucocorticoid treatment is associated with adverse metabolic consequences such as hypertension, overweight, reduced glucose tolerance, diabetes mellitus and ultimately increased mortality in cardiovascular disease. Here we review the evidence of detrimental effects of hormone replacement therapy in adrenal insufficiency (AI). Registry studies indicate increased cardiovascular mortality, hypertension, diabetes, and dyslipidemia in both primary and secondary AI, but when cohorts with carefully characterized patients are studied the picture is less clear, and recently patients with primary AI was reported to have less hypertension and lower body mass index than controls. Whether near physiological replacement therapy increase long-term cardiovascular morbidity and mortality in AI is still unclear.

10.
Ann Endocrinol (Paris) ; 79(3): 157-163, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29631795

RESUMO

Autoimmunity against the adrenal cortex is the leading cause of Addison's disease in industrialized countries, with prevalence estimates ranging from 93-220 per million in Europe. The immune-mediated attack on adrenocortical cells cripples their ability to synthesize vital steroid hormones and necessitates life-long hormone replacement therapy. The autoimmune disease etiology is multifactorial involving variants in immune genes and environmental factors. Recently, we have come to appreciate that the adrenocortical cell itself is an active player in the autoimmune process. Here we summarize the complex interplay between the immune system and the adrenal cortex and highlight unanswered questions and gaps in our current understanding of the disease.


Assuntos
Doença de Addison/etiologia , Doenças Autoimunes/etiologia , Doença de Addison/tratamento farmacológico , Doença de Addison/epidemiologia , Doença de Addison/imunologia , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/epidemiologia , Doenças Autoimunes/imunologia , Autoimunidade , Europa (Continente)/epidemiologia , Terapia de Reposição Hormonal , Humanos
11.
Nutrition ; 49: 66-73, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29522979

RESUMO

OBJECTIVES: On the basis of the immunomodulatory actions of vitamin D (VD), we investigated the effects of high-dose VD therapy over a 3 mo period on the immune response in patients with Addison's disease (AD). METHODS: This randomized, controlled, crossover trial included 13 patients with AD who received either cholecalciferol (4000 IU/d) for 3 mo followed by 3 mo placebo oil or the sequential alternative placebo followed by verum. Glucocorticoid replacement doses remained stable. The primary outcome measures were changes in 25-hydroxyvitamin D3 (25(OH)D3) levels and immune cells including T helper cells (Th; CD3+CD4+), late-activated Th cells (CD3+CD4+HLA-DR+), regulatory T cells (CD3+CD4+CD25brightCD127dim/neg), cytotoxic T cells (Tc; CD3+CD8+), late-activated Tc cells (CD3+CD8+HLA-DR+), and monocytes. The explorative analysis included the correlation of changes with VD-related gene polymorphisms and 21-hydroxylase antibody titers. RESULTS: Ten of 13 patients (77%) were VD deficient. Median 25(OH)D3 concentrations increased significantly to 41.5 ng/ml (median changes: 19.95 ng/ml; P = 0.0005) after 3 mo of cholecalciferol treatment. Within the T-cells, only the late-activated Th (median changes: 1.6%; P = 0.02) and late-activated Tc cells (median changes: 4.05%; P = 0.03) decreased, whereas monocytes (median changes: 1.05%; P = 0.008) increased after VD therapy. T-cell changes were associated with two polymorphisms (CYP27B1-rs108770012 and VDR-rs10735810), but no changes in the 21-hydroxylase antibody titers were observed. CONCLUSIONS: Three months of treatment with cholecalciferol achieved sufficient 25(OH)D3 levels and can regulate late-activated T-cells and monocytes in patients with AD. Explorative analysis revealed potential genetic contributions. This pilot trial provides novel insights about immunomodulation in AD.

13.
J Oral Microbiol ; 10(1): 1442986, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29503707

RESUMO

Background: Autoimmune polyendocrine syndrome type-1 (APS-1) is a rare, childhood onset disease caused by mutations in the Autoimmune Regulator gene. The phenotypic expression is highly variable and includes disease manifestations in the oral cavity, including mucocutaneous candidiasis. Increasing evidence suggests a potential role of the skin, oral and gut microbiotas in the pathogenesis of autoimmunity. To date, no information exists regarding the oral microbiota in APS-1. Objective: To assess the bacterial microbiota of whole saliva in APS-1 patients by using high throughput sequencing. Design: Whole unstimulated saliva was collected from 10 APS-1 patients and 17 healthy controls and examined by high throughput sequencing of the hypervariable region V1-V2 of 16S rRNA using the 454 GS Junior system. Metastats (http://cbcb.umd.edu/software/metastats) was used to analyse the pyrosequencing reads. Results: A reduction in the total number of bacterial genera and species was detected in APS-1 compared to healthy controls. The proportion of the major phyla Firmicutes was higher (60% vs 41%, p = 0.002) and Bacteroidetes lower (15% vs 28%, p = 0.007) in APS-1 compared to healthy controls. On the genus level, Streptococcus and Gemella were prevalent in APS-1. Conclusion: Our findings indicate a significantly altered oral microbiota in APS-1.

14.
Endocr Connect ; 7(3): 413-424, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29440130

RESUMO

BACKGROUND: Primary aldosteronism (PA) is associated with increased cardiovascular morbidity, presumably due to left ventricular (LV) hypertrophy and fibrosis. However, the degree of fibrosis has not been extensively studied. Cardiac magnetic resonance imaging (CMR) contrast enhancement and novel sensitive T1 mapping to estimate increased extracellular volume (ECV) are available to measure the extent of fibrosis. OBJECTIVES: To assess LV mass and fibrosis before and after treatment of PA using CMR with contrast enhancement and T1 mapping. METHODS: Fifteen patients with newly diagnosed PA (PA1) and 24 age- and sex-matched healthy subjects (HS) were studied by CMR with contrast enhancement. Repeated imaging with a new scanner with T1 mapping was performed in 14 of the PA1 and 20 of the HS median 18 months after specific PA treatment and in additional 16 newly diagnosed PA patients (PA2). RESULTS: PA1 had higher baseline LV mass index than HS (69 (53-91) vs 51 (40-72) g/m2; P < 0.001), which decreased significantly after treatment (58 (40-86) g/m2; P < 0.001 vs baseline), more with adrenalectomy (n = 8; -9 g/m2; P = 0.003) than with medical treatment (n = 6; -5 g/m2; P = 0.075). No baseline difference was found in contrast enhancement between PA1 and HS. T1 mapping showed no increase in ECV as a myocardial fibrosis marker in PA. Moreover, ECV was lower in the untreated PA2 than HS 10 min post-contrast, and in both PA groups compared with HS 20 min post-contrast. CONCLUSION: Specific treatment rapidly reduced LV mass in PA. Increased myocardial fibrosis was not found and may not represent a common clinical problem.

15.
J Clin Endocrinol Metab ; 103(4): 1696-1703, 2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29452421

RESUMO

Background: The cosyntropin test is used to diagnose adrenal insufficiency (AI) and nonclassical congenital adrenal hyperplasia (NCCAH). Current cutoffs for cortisol and 17-hydroxyprogesterone (17-OHP) are derived from nonstandardized immunoassays. Liquid chromatography tandem mass spectrometry (LC-MS/MS) offers direct measurement of steroids, prompting the need to re-establish normal ranges. Objective: The goal of this study was to define cutoff values for cortisol and 17-OHP in serum by LC-MS/MS 30 and 60 minutes after intravenous administration of 250 µg tetracosactide acetate to healthy volunteers and to compare the results with LC-MS/MS with routine immunoassays. Methods: Cosyntropin testing was performed in healthy subjects (n = 138) and in patients referred for evaluation of adrenocortical function (n = 94). Steroids were assayed by LC-MS/MS and compared with two immunoassays used in routine diagnostics (Immulite and Roche platforms). The cutoff level for cortisol was defined as the 2.5% percentile in healthy subjects not using oral estrogens (n = 121) and for 17-OHP as the 97.5% percentile. Results: Cortisol cutoff levels for LC-MS/MS were 412 and 485 nmol/L at 30 and 60 minutes, respectively. Applying the new cutoffs, 13 of 60 (22%) subjects who had AI according to conventional criteria now had a normal test result. For 17-OHP, the cutoff levels were 8.9 and 9.0 nmol/L at 30 and 60 minutes, respectively. Conclusions: LC-MS/MS provides cutoff levels for cortisol and 17-OHP after cosyntropin stimulation that are lower than those based on immunoassays, possibly because cross-reactivity between steroid intermediates and cortisol is eliminated. This reduces the number of false-positive tests for AI and false-negative tests for NCCAH.


Assuntos
17-alfa-Hidroxiprogesterona/sangue , Hiperplasia Suprarrenal Congênita/diagnóstico , Insuficiência Adrenal/diagnóstico , Cosintropina , Hidrocortisona/sangue , Adolescente , Hiperplasia Suprarrenal Congênita/sangue , Insuficiência Adrenal/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Cromatografia Líquida , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Espectrometria de Massas em Tandem , Adulto Jovem
16.
J Clin Endocrinol Metab ; 103(1): 179-186, 2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-29069385

RESUMO

Context: Autoimmune polyendocrine syndrome type 1 (APS1) is a monogenic disorder that features autoimmune Addison disease as a major component. Although APS1 accounts for only a small fraction of all patients with Addison disease, early identification of these individuals is vital to prevent the potentially lethal complications of APS1. Objective: To determine whether available serological and genetic markers are valuable screening tools for the identification of APS1 among patients diagnosed with Addison disease. Design: We systematically screened 677 patients with Addison disease enrolled in the Swedish Addison Registry for autoantibodies against interleukin-22 and interferon-α4. Autoantibody-positive patients were investigated for clinical manifestations of APS1, additional APS1-specific autoantibodies, and DNA sequence and copy number variations of AIRE. Results: In total, 17 patients (2.5%) displayed autoantibodies against interleukin-22 and/or interferon-α4, of which nine were known APS1 cases. Four patients previously undiagnosed with APS1 fulfilled clinical, genetic, and serological criteria. Hence, we identified four patients with undiagnosed APS1 with this screening procedure. Conclusion: We propose that patients with Addison disease should be routinely screened for cytokine autoantibodies. Clinical or serological support for APS1 should warrant DNA sequencing and copy number analysis of AIRE to enable early diagnosis and prevention of lethal complications.


Assuntos
Doença de Addison/diagnóstico , Autoanticorpos/sangue , Biomarcadores/sangue , Citocinas/imunologia , Programas de Rastreamento , Poliendocrinopatias Autoimunes/diagnóstico , Sistema de Registros , Doença de Addison/sangue , Doença de Addison/imunologia , Autoanticorpos/imunologia , Estudos de Casos e Controles , Seguimentos , Humanos , Poliendocrinopatias Autoimunes/sangue , Poliendocrinopatias Autoimunes/imunologia , Prognóstico , Suécia
17.
J Clin Endocrinol Metab ; 102(9): 3546-3556, 2017 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-28911151

RESUMO

Context: Autoimmune polyendocrine syndrome type 1 (APS-1) is a rare monogenic autoimmune disease caused by mutations in the autoimmune regulator (AIRE) gene and characterized by chronic mucocutaneous candidiasis, hypoparathyroidism, and primary adrenal insufficiency. Comprehensive characterizations of large patient cohorts are rare. Objective: To perform an extensive clinical, immunological, and genetic characterization of a large nationwide Russian APS-1 cohort. Subjects and Methods: Clinical components were mapped by systematic investigations, sera were screened for autoantibodies associated with APS-1, and AIRE mutations were characterized by Sanger sequencing. Results: We identified 112 patients with APS-1, which is, to the best of our knowledge, the largest cohort described to date. Careful phenotyping revealed several additional and uncommon phenotypes such as cerebellar ataxia with pseudotumor, ptosis, and retinitis pigmentosa. Neutralizing autoantibodies to interferon-ω were found in all patients except for one. The major Finnish mutation c.769C>T (p.R257*) was the most frequent and was present in 72% of the alleles. Altogether, 19 different mutations were found, of which 9 were unknown: c.38T>C (p.L13P), c.173C>T (p.A58V), c.280C>T (p.Q94*), c.554C>G (p.S185*), c.661A>T (p.K221*), c.821del (p.Gly274Afs*104), c.1195G>C (p.A399P), c.1302C>A (p.C434*), and c.1497del (p.A500Pfs*21). Conclusions: The spectrum of phenotypes and AIRE mutation in APS-1 has been expanded. The Finnish major mutation is the most common mutation in Russia and is almost as common as in Finland. Assay of interferon antibodies is a robust screening tool for APS-1.


Assuntos
Predisposição Genética para Doença/epidemiologia , Mutação , Poliendocrinopatias Autoimunes/epidemiologia , Poliendocrinopatias Autoimunes/genética , Fatores de Transcrição/genética , Adolescente , Adulto , Idade de Início , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Genótipo , Humanos , Masculino , Linhagem , Fenótipo , Poliendocrinopatias Autoimunes/diagnóstico , Prevalência , Doenças Raras , Medição de Risco , Federação Russa/epidemiologia , Análise de Sobrevida , Adulto Jovem
19.
Front Immunol ; 8: 976, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28861084

RESUMO

High titer autoantibodies produced by B lymphocytes are clinically important features of many common autoimmune diseases. APECED patients with deficient autoimmune regulator (AIRE) gene collectively display a broad repertoire of high titer autoantibodies, including some which are pathognomonic for major autoimmune diseases. AIRE deficiency severely reduces thymic expression of gene-products ordinarily restricted to discrete peripheral tissues, and developing T cells reactive to those gene-products are not inactivated during their development. However, the extent of the autoantibody repertoire in APECED and its relation to thymic expression of self-antigens are unclear. We here undertook a broad protein array approach to assess autoantibody repertoire in APECED patients. Our results show that in addition to shared autoantigen reactivities, APECED patients display high inter-individual variation in their autoantigen profiles, which collectively are enriched in evolutionarily conserved, cytosolic and nuclear phosphoproteins. The APECED autoantigens have two major origins; proteins expressed in thymic medullary epithelial cells and proteins expressed in lymphoid cells. These findings support the hypothesis that specific protein properties strongly contribute to the etiology of B cell autoimmunity.

20.
Autoimmunity ; 50(4): 223-231, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28557628

RESUMO

Autoimmune polyendocrine syndrome type 1 (APS1) is a rare monogenic autoimmune disorder caused by mutations in the autoimmune regulator (AIRE) gene. High titer autoantibodies are a characteristic feature of APS1 and are often associated with particular disease manifestations. Pituitary deficits are reported in up to 7% of all APS1 patients, with immunoreactivity to pituitary tissue frequently reported. We aimed to isolate and identify specific pituitary autoantigens in patients with APS1. Immunoscreening of a pituitary cDNA expression library identified endothelin-converting enzyme (ECE)-2 as a potential candidate autoantigen. Immunoreactivity against ECE-2 was detected in 46% APS1 patient sera, with no immunoreactivity detectable in patients with other autoimmune disorders or healthy controls. Quantitative-PCR showed ECE-2 mRNA to be most abundantly expressed in the pancreas with high levels also in the pituitary and brain. In the pancreas ECE-2 was co-expressed with insulin or somatostatin, but not glucagon and was widely expressed in GH producing cells in the guinea pig pituitary. The correlation between immunoreactivity against ECE-2 and the major recognized clinical phenotypes of APS1 including hypopituitarism was not apparent. Our results identify ECE-2 as a specific autoantigen in APS1 with a restricted neuroendocrine distribution.


Assuntos
Autoantígenos/imunologia , Enzimas Conversoras de Endotelina/imunologia , Poliendocrinopatias Autoimunes/imunologia , Adolescente , Processamento Alternativo , Autoanticorpos/imunologia , Autoantígenos/genética , Autoimunidade , Criança , Enzimas Conversoras de Endotelina/genética , Feminino , Expressão Gênica , Perfilação da Expressão Gênica , Loci Gênicos , Humanos , Imuno-Histoquímica , Masculino , Fenótipo , Hipófise/imunologia , Hipófise/metabolismo , Poliendocrinopatias Autoimunes/diagnóstico , Poliendocrinopatias Autoimunes/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA