Autoimmunity in isolated Addison's disease and in polyglandular autoimmune diseases type 1, 2 and 4.
ABSTRACT Sera from 300 Italian patients with Addison's disease were collected over a 30 year period. Among these patients, 82% had autoimmune disease, 13% had tuberculosis and 5% had another causal condition. In 59% of the cases, autoimmune disease was associated with the autoimmune manifestations contributing to the description of polyglandular autoimmune disease (PGAD). In PGAD type 1, the disease was associated with chronic candidiasis and/or chronic hypoparathyroidism. In PGAD type 2, the patients had autoimmune thyroid disease and/or diabetes mellitus type 1, and in PGAD type 4, they presented a combination with other autoimmune diseases excluding those previously mentioned. Finally, the autoimmune disease was apparently isolated in 41% of the cases. In addition, patients with these four forms of disease exhibited a different genetic pattern, sex distribution, and age at presentation in addition to minor frequency of autoimmune diseases. Adrenal cortex autoantibodies directed against 21-hydroxylase were common serological markers for these four main clinical forms, showing a very high frequency at clinical onset of adrenal insufficiency. In some patients, steroid-producing cell autoantibodies were also present and correlated with gonadal failure and they recognize of 17alpha-hydroxylase or P450 side chain cleavage enzymes as target antigens.
Article: Autoimmune polyendocrine syndrome type 1 in Norway: phenotypic variation, autoantibodies, and novel mutations in the autoimmune regulator gene.[show abstract] [hide abstract]
ABSTRACT: The autoimmune polyendocrine syndrome type I (APS I) is a rare disease that previously was difficult to diagnose. Autoantibody screening as well as mutational analysis of the disease gene autoimmune regulator (AIRE) are important diagnostic tools for this life-threatening syndrome. The objective of the study was to identify all patients with APS I in Norway and correlate their clinical features with their autoantibody profiles and mutations in the AIRE gene. We identified 36 Norwegian patients from 24 families with APS I (20 males, 16 females) during a nationwide survey for patients with Addison's disease and polyendocrine syndromes, seven of them only after their death. Clinical data were collected from questionnaires and patient records. AIRE mutations were determined by DNA sequencing. Most autoantibodies were measured in RIAs against recombinant autoantigens, but anti-type I interferon (IFN) antibodies were titrated in ELISA or antiviral interferon neutralization assays. The prevalence of APS I in Norway was estimated to be about 1:90,000. Several patients exhibited a milder phenotype with few APS I disease components and onset only in late adolescent or adulthood. The others showed about the same distribution of disease components as reported in Finnish patients. Eleven different mutations were identified in the AIRE gene, six of these were novel, i.e. c.22C>T (p.Arg8Cys), c.290T>C (p.Leu97Pro), c.402delC (p.Ser135GlnfsX12), c.879 + 1G>A (p.IVS7 + 1G>A), c.1249dupC (p.Leu417ProfsX7), and c.1336T>G (p.Cys446Gly). The 13-bp deletion in exon 8 (c.967-979del13) was the most prevalent mutation, present in 23 of 48 (48%) of the alleles. The presence of neutralizing autoantibodies against IFN-omega was the most specific marker of APS I, being found in all but one Norwegian patient. Some other common APS I-associated autoantibodies appeared de novo during long-term follow-up of younger patients. Norwegian patients with APS I clinically resemble those from Finland and other European countries, but some have milder phenotypes. In total, six new mutations were identified in the Norwegian APS I patients. Anti-type I IFN autoantibodies are easily detectable; their APS I specificity and persistently high titers render them reliable markers of APS I, even in prodromal or atypical cases. Both the clinical features and the AIRE mutations are more diverse in the Norwegian population than previously thought.Journal of Clinical Endocrinology & Metabolism 02/2007; 92(2):595-603. · 6.50 Impact Factor
[show abstract] [hide abstract]
ABSTRACT: Autoimmune polyendocrinopathy type II is rarely reported in Chinese patients. A 42-year-old Chinese woman with a history of Hashimoto's thyroiditis and hypogonadotropic hypogonadism presented with pneumonia. During hospitalisation, she went into an adrenal crisis and diabetic ketoacidosis. Subsequent dynamic hormonal tests revealed primary and secondary adrenal insufficiency. She also had pernicious anaemia, possible alopecia areata, and myasthenia gravis. This constellation of multiple endocrine and non-endocrine disorders led to the diagnosis of autoimmune polyendocrinopathy type II. As the syndrome can be lethal, it is important to maintain a high index of suspicion, enabling early diagnosis and the appropriate replacement therapy, to ensure a successful outcome.Hong Kong medical journal = Xianggang yi xue za zhi / Hong Kong Academy of Medicine 11/2006; 12(5):385-7.
Article: Growth hormone impaired secretion and antipituitary antibodies in patients with coeliac disease and poor catch-up growth after a long gluten-free diet period: a causal association?[show abstract] [hide abstract]
ABSTRACT: Coeliac disease (CD) is usually associated with impaired growth in children. A gluten-free diet (GFD) induces a catch-up growth with the recovery of height in about 2 years. AIM AND DISCUSSION: The lack of the height improvement has been related to growth hormone (GH) secretion impairment. CD is an autoimmune disease often associated with other endocrine and non-endocrine autoimmune disease. The aim of this study was to evaluate antipituitary autoantibodies (APA) and antihypothalamus autoantibodies in CD children with poor clinical response to a GFD and growth hormone deficiency (GHD). We diagnosed CD on the basis of specific antibodies and endoscopic biopsies in 130 patients aged 1-15 years. Seven CD children, without catch-up growth after at least 12-months GFD, were tested for GH secretion and, in five out of seven patients, the diagnosis of GHD was made in the absence of metabolic and systemic diseases. APA and antihypothalamus antibodies were detected by the indirect immunofluorescence method in the seven CD children without catch-up growth factor and in 25 CD children without growth impairment matched for sex and age, and in 58 healthy children as control groups. APA resulted positive at high titres in four out of five CD-GHD patients and were also positive at low titres (<1:8) in three of only CD children and in two out of 58 controls. Hypothalamic-pituitary magnetic resonance imaging (MRI) was normal in all patients except in one with cystic pineal. APA have been previously detected not only in adults with GHD, but also in idiopathic GHD children, suggesting the occurrence of an autoimmune hypophysitis in these patients. In our study, the presence of APA in CD children without catch-up growth after GFD seems to be able to identify an autoimmune form of hypophysitis involving the somatotrophs cells.European Journal of Pediatrics 12/2006; 165(12):897-903. · 1.88 Impact Factor