1,721,084 research outputs found
Anti-Pancreatic islet cell antibodies in type I diabetes mellitus and in latent autoimmune diabetes in adults (LADA) [Autoanticorpi anti-insula pancreatica nel Diabete Mellito di Tipo 1 e nel latent autoimmune diabetes in adults (LADA)]
No full textIslet autoimmunity is made evident by the appearance of islet cell antibodies directed against insulin (IAA), glutamic acid decarboxylase (GADA), protein tyrosine phosphatase IA-2 (IA-2A) and other autoantigens. Islet autoantibodies are not pathogenic, but they are useful markers of the ongoing autoimmune process. IAA and IA-2A are predominantly detected in childhood type 1 diabetes mellitus (T1DM), while frequency of GADA is not affected by age at disease onset. In adult-onset T1DM patients, GADA is the immune marker at higher diagnostic sensitivity. In adult diabetic patients who do not require insulin treatment for at least 6 months after diagnosis, GADA identify the so-called latent autoimmune diabetes in adults (LADA). In over 80% of cases, LADA patients develop insulin dependency within a few years after the diagnosis and have an increased risk for development of other organ-specific autoimmune diseases. High GADA titres identify a subgroup of LADA patients with low body mass index (BMI), low C-peptide levels and increased frequency of T1DM-related HLA class II haplotypes. Therefore, GADA assay should be offered to adult diabetic patients to identify cases with latent autoimmunity, and in case of positivity, screening for other autoimmune diseases should be carried out. Commercial kits for GADA and IA-2A are currently available. The choice of the specific assay should take into consideration the proficiency in international workshops of standardization, such as the Diabetes Antibody Standardization Program (DASP)
Addison's Disease
No full textAutoimmune Addison's disease (AAD) represents 70-90% of all cases of primary adrenal insufficiency (PAI) in western countries and Japan. The adrenal autoimmune process is made evident by the appearance of autoantibodies, directed against steroid-21-hydroxylase (21OHAb), the gold marker to identify AAD in patients with clinical and biochemical signs of adrenal insufficiency. 21OHAb have no major pathogenic role, and the disease is thought to be caused by a cell-mediated immune process. In 21OHAb-negative patients, adrenal imaging and very long-chain fatty acids determination should be performed to exclude other causes of PAI such as posttuberculosis Addison's disease or X-linked adrenoleukodystrophy. AAD is a major component of autoimmune polyendocrine syndrome (APS) type 1 and type 2. Isolated AAD and APS2-related AAD are strongly associated with HLA-DRB1 (star)0301 DQA1 (star)0501- DQB1 (star)0201 (DR3-DQ2) and DRB1 (star)04-DQA1 (star)0301 DQB1 (star)0302 (DR4-DQ8). HLA- DRB1 (star)0403 is strongly protective for the development of AAD. Other genetic factors that contribute to the risk of AAD include MICA5.1, and the polymorphisms of the CTLA-4, PTPN22, and MHC2TA genes. Around two-thirds of AAD subjects show clinical or biochemical signs of other autoimmune diseases, the most common being thyroid autoimmune diseases, type 1 diabetes mellitus, and primary ovarian insufficiency. Presence of 21OHAb in subjects with no clinical signs of adrenal insufficiency and with normal basal cortisol levels identifies the so-called subclinical AAD. In subjects with subclinical AAD, a stimulation test with 1 mu g of synthetic ACTH should be performed to discriminate between an early and potentially reversible adrenal dysfunction and a progressive form of the disease
MICA gene: A new polymorphic major histocompatibility complex (MHC)susceptibility gene for autoimmune endocrine diseases
No full textAutoantibody profile and epitope mapping in latent autoimmune diabetes in adults
No full textThe presence of islet cell autoantibodies in adult diabetic subjects who do not require insulin treatment for at least six months after the initial clinical diagnosis identifies the so-called latent autoimmune diabetes in the adult (LADA). Glutamic acid decarboxylase autoantibodies (GAD65Ab) are the best immune marker to identify LADA patients, while other islet autoantibodies, such as IA-2 autoantibodies, have a very low diagnostic sensitivity. Islet cell antibodies, as detected by indirect immunofluorescence, may improve the diagnostic specificity of the immune analysis when detected in GAD65Ab-positive patients. Although the majority of LADA patients progresses towards insulin dependency within a few years after the diagnosis, this form of diabetes is heterogeneous. The presence of high titers of GAD65Ab and/or GAD65Ab directed towards COOH-terminal epitopes of the autoantigen (GAD65-CAb) identifies a subgroup of LADA patients with clinical characteristics similar to those of typical type 1 diabetes and at very high risk of progression toward insulin dependency. On the other hand, low titers of GAD65Ab, or the exclusive presence of GAD65Ab directed to middle epitopes of the autoantigen, characterizes LADA patients with clinical characteristics almost indistinguishable from those of GAD65Ab-negative type 2 diabetic patients. LADA subjects, especially in the presence of high titers of GAD65Ab and/or GAD65-CAb, have an increased risk for other organ-specific autoimmune diseases such as thyroid autoimmune diseases or autoimmune Addison's. LADA should be considered a major component of the autoimmune polyendocrine syndromes, and screening for other autoimmune diseases should be performed in all LADA patient
Adrenal autoimmunity and correlation with adrenal dysfunction
No full textPrimary adrenal insufficiency (Addison's disease) affects approximately 1 in 8500 persons in the general population. In the western countries, 70-75% of cases of Addison's disease are caused by autoimmune destruction of the adrenal cortex. The presence of adrenal cortex autoantibodies (ACA), as detected by indirect immunofluorescence, is a good marker of adrenal autoimmunity. The enzyme steroid-21-hydroxylase (21OH) is a major target of ACA and 21OH autoantibodies (21OHAb) have been found in 80-90% of subjects with clinically idiopathic Addison's disease and in almost all cases with short disease duration. Autoantibodies to other steroidogenic enzymes, such as 17α-hydroxylase (17αOHAb) and side-chain cleavage enzyme (P450sccAb) are often detected in patients with autoimmune polyglandular syndrome type I (APS I) or with APS II with gonadal insufficiency, but they are rarely found in isolated Addison's or in APS II without gonadal insufficiency. The genetic risk for autoimmune Addison's disease is associated with HLA-DR3-DQ2 and with the allele 5.1 of the MHC class I chain-related A (MIC-A) gene. The predictive value of genetic markers for Addison's disease is very low. Adrenal autoantibodies are found in approximately 1-1.5% of subjects with other organ-specific autoimmune diseases. The predictive value of ACA/21OHAb is very high (90%) in children, but is not higher than 20-30% in adult subjects. This is probably related to a slow, chronic process in adults that requires longer follow-up periods. The level of adrenal autoantibodies correlate with the degree of adrenal dysfunction and, using immune and biochemical markers, the natural history of autoimmune Addison's is described in this review. The clinical applications of the adrenal autoantibody assays are discussed
Sindrome da insufficienza corticosurrenalica primitiva: nuovi concetti eziopatogenetici e diagnostici
No full text- …
