Type I diabetes mellitus may represent a heterogeneous disorder with a distinct pathogenesis in patients with young and adult onset of the disease. To investigate whether serological markers directed to different autoantigens have the potential to distinguish acute onset from slowly progressive Type I diabetes we analysed antibodies to tyrosine phosphatases IA-2/ICA512 (IA-2A) and IA-2β/phogrin (IA2βA), antibodies to GAD65 (GADA) and cytoplasmic islet cell antibodies (ICA) in a non-selected group of diabetic patients clinically classified as having Type I or Type II diabetes at diagnosis. Both IA-2A and IA-2βA were found to be positively associated with onset before the age of 20 years and the presentation of classical features of Type I diabetes. In Type I diabetes 56 % (112/200) of patients were positive for IA-2A and 38 % (76/200) for IA-2βA. In contrast, only 1 of 785 (0.1 %) patients with Type II diabetes had IA-2A and all of them were negative for IA-2βA (p < 0.001). Among the patients with Type II diabetes 7.6 % (n = 60) were ICA positive and 2.8 % (n = 22) had GADA suggesting the presence of slowly progressive Type I diabetes. GADA were found in 8 of 60 (13.3 %) ICA positive subjects which was lower than the percentage detected in patients with acute onset of diabetes (115/157 73.2 %) (p < 0.001). Blocking of double antibody positive sera showed that only 3 of 8 (37.5 %) patients with slowly progressive diabetes had ICA restricted to GAD or IA-2 whereas ICA were completely inhibited in 12 of 20 (60.0 %) patients with Type I diabetes. Among 193 patients with Type II diabetes available for follow-up, 35 % of ICA positives, 58 % of GADA positives and 60 % of those positive for both markers required insulin by 3 years. However, using strict criteria for the switch to insulin treatment the corresponding sensitivity of each marker was only low (9 %, 10 % and 5 %).
We show that clinical subtypes of Type I diabetes are associated with distinct humoral autoimmunity. IA-2A and GADA were associated with classical features of Type I diabetes whereas GADA and an uncharacterized ICA subspecificity indicate slowly progressive disease. [Diabetologia (1998) 41: 891–897]
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.
"Our result also indicated the increase of BBB permeability after EV71 infection in infant mice and further more, the increase of BBB permeability after EV71 infection could result in the entrance and localization of the IgG into brain tissues. Autoimmune disease was reported in many previous studies, such as celiac disease, sclerosis, encephalitis, Diabetes mellitus [44-48]. As the BBB in infant can be destructed upon EV71 infection and the EV71 can induce cross-reactivity IgG, therefore, whether the intracranial entry of EV71 elicited IgG is one of the mechanisms of neurological pathogeneses in HFMD patients was remained to be clarified in further study. "
[Show abstract][Hide abstract] ABSTRACT: EV71 occasionally cause a series of severe neurological symptoms, including aseptic meningitis, encephalitis, and poliomyelitis-like paralysis. However, the neurological destruction mechanism was remained to be clarified. This study described the cross reaction between EV71 induced IgG and human brain tissue.
Cross reaction of the IgG from 30 EV71 infected patients' sera to human tissues of cerebra was observed, which suggested that some EV71 antigens could induce IgG cross-reactivity to human cerebra. To identify the regions of EV71 virus that containing above antigens, the polypeptide of virus was divided into 19 peptides by expression in prokaryotes cell. Mouse anti-sera of these peptides was prepared and applied in immunohistochemical staining with human adult and fetus brain tissue, respectively. The result indicated the 19 peptides can be classified into three groups: strong cross-reactivity, weak cross-reactivity and no cross-reactivity with human brain tissue according the cross reaction activity. Then, the increased Blood Brain Barrier (BBB) permeability and permits IgG entry in neonatal mice after EV71 infection was determined.
EV71 induced IgG could enter BBB and cross-reacted with brain tissue in EV71 infected neonatal mice, and then the peptides of EV71 that could induce cross-reactivity with brain tissue were identified, which should be avoided in future vaccine designing.
"In adult patients one or more of these antibodies are reported at clinical onset in 66–93% of the cases3456. Specifically, Pancreatic autoantibodies in Italian patients with newly diagnosed type 1 diabetes mellitus over the age of 20 years O R I G I N A L C. Betterle ( autoantibodies to islet-cells (ICA) are detectable in 46–73% [3–5, 7, 8], to glutamic acid decarboxylase (GADA) in 29–84%3456789, to tyrosine-phosphatase (IA2A) in 0–45%4567 9] and to insulin (IAA) in 0–29% of patients [3, 5]. The aim of this study was to assess the prevalence of different pancreatic autoantibodies in adult Italian patients with T1DM at clinical onset in order to determine which was the most advantageous cost/benefit autoantibody combination for the diagnosis of the autoimmune form of diabetes. "
[Show abstract][Hide abstract] ABSTRACT: The aim was to estimate the prevalence of the serological markers of pancreatic autoimmunity in a cohort of Italian patients with type 1 diabetes mellitus occurring after 20 years of age in order to determine the prevalence of autoimmune diabetes and the most sensitive autoantibody combination to be employed for the diagnosis. We investigated 57 patients (31 males and 26 females) at clinical diagnosis of type 1 diabetes. 35 patients were 21-40 years and 22 were 41-72 years of age. Autoantibodies to islet-cells (ICA) were detected by indirect immunofluorescence, while those against glutamic acid decarboxylase (GADA), tyrosine-phosphatase (IA2A) and insulin (IAA) were detected by radiobinding assays. A positive test for at least one of the pancreatic autoantibodies was found in 45 of the 57 patients (78.9%). Coupling two antibody tests, GADA and/or IAA were found in 73.7%, ICA and/or GADA in 71.9%, while GADA and/or IA2A were found in 70.2% of the patients. The most frequently positive test was for GADA (66.7%). In general, the frequency of diabetes-related antibodies was higher in the 21-40-year-old group compared to the 41-72-year-old group and in females than males. Based on the detection of pancreatic autoantibodies determination, the great majority of the adult patients with recent onset type 1 diabetes were found to be autoimmune in nature. The best cost/benefit combination is provided by coupling the detection of GADA and ICA.
Full-text · Article · Dec 2006 · Acta Diabetologica
"Type 1 diabetes, is a chronic disease characterized by the autoimmune destruction of pancreatic β-cells resulting in complete insulin deficiency . The disease is quite heterogeneous in its clinical expression . A large body of evidence indicates that inherited genetic factors influence both susceptibility and resistance to the disease. "
[Show abstract][Hide abstract] ABSTRACT: The cytotoxic T lymphocyte-associated antigen 4 gene (CTLA-4) encode the T cell receptor involved in the control of T cell proliferation and mediates T cell apoptosis. The receptor protein is a specific T lymphocyte surface antigen that is detected on cells only after antigen presentation. Thus, CTLA-4 is directly involved in both immune and autoimmune responses and may be involved in the pathogenesis of multiple T cell-mediated autoimmune disorders. There is polymorphism at position 49 in exon 1 of the CTLA-4 gene, providing an A-G exchange. Moreover, we assessed the CTLA-4 49 (Thr/Ala) polymorphism in diabetic patients and first-degree relatives as compared to control subjects.
Three loci (HLA-DQB1, DQA1 and CTLA-4) were analysed in 62 type 1 diabetic patients, 72 first-degree relatives and 84 nondiabetic control subjects by means of PCR-RFLP.
A significant enrichment in DQB1 alleles encoding for an amino acid different from Asp in position 57 (NA) and DQA1 alleles encoding for Arg in position 52 was observed in diabetic subjects and first-degree relatives as compared to controls. The genotype and allele frequencies of these polymorphisms in type 1 diabetic patients and first-degree relatives differed significantly from those of controls (p < 0.001 and 0.05 respectively). CTLA-49 Ala alleles frequencies were 75.8% in type 1 diabetic patients and 68.1% in first-degree relatives in comparison to 35.7% in control subjects. The Ala/Ala genotype conferred a relative risk of 18.8 (p < 0.001).
The CTLA-4 49 Ala allele confers an increased risk of type 1 diabetes, independent of age and HLA-DQ genetic markers.
Full-text · Article · Feb 2002 · International Journal of Experimental Diabetes Research