Current cases in which epitope mimicry is considered as a component cause of autoimmune disease: immune-mediated (type 1) diabetes

Kukreja, Anjli; Maclaren, Noel K.

doi:10.1007/pl00000715

Cited by 43 publications

(26 citation statements)

References 60 publications

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“…Some studies have suggested that the T h 2 profile in some way is protective against the aggressive damage inflicted on the insulin-producing cells [25,26,27,28,29]. Furthermore, in our study the LADA patients, who expressed more IgG 4 , also had better preserved beta cell function at clinical onset.…”

Section: Discussionsupporting

confidence: 64%

IgG4-subclass of glutamic acid decarboxylase antibody is more frequent in latent autoimmune diabetes in adults than in type 1 diabetes

et al. 2004

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Aims/hypothesis. Glutamic acid decarboxylase autoantibodies (GADA) are the most frequent beta-cell-specific autoantibodies in type 1 diabetes and in latent autoimmune diabetes in adults (LADA). The autoimmune attack on pancreatic islet cells is associated with a T helper 1 cell (T h 1) response, mainly represented by IgG 1 -subclass in humans. It has been proposed that the presence of IgG 4 may be associated with a T h 2 response. The aim of our study was to compare the GADA IgG-subclass distribution between adult patients with type 1 diabetes and LADA. Methods. Patients with type 1 diabetes (n=45) and patients with LADA (n=60) were included. Radioimmunoprecipitation assay with IgG-subclass specific Sepharose (IgG 1 , IgG 2 , IgG 3 and IgG 4 ) was used to precipitate the antibody/antigen-complex.Results. We only detected IgG 4 -subclass of GADA in subjects with LADA (26.7%; p<0.001). IgG 1 was the most common GADA-subclass in both groups, however IgG 1 as the solely expressed subclass was more common among type 1 diabetic patients (77.8%; p<0.05). The rank order of the frequencies of IgG-subclasses in type 1 diabetes was IgG 1 >IgG 3 >IgG 2 >IgG 4 and in LADA patients IgG 1 >IgG 4 >IgG 2 >IgG 3 . Conclusions/interpretation. The difference in GADA IgG-subclasses could indicate a different immune response, possibly an altered balance between T h 1 and T h 2 cytokine profile in pancreatic islets. This difference could contribute to the slower rate of beta cell destruction in LADA patients, as reflected by a higher C-peptide level at clinical onset.

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Section: Discussionsupporting

confidence: 64%

IgG4-subclass of glutamic acid decarboxylase antibody is more frequent in latent autoimmune diabetes in adults than in type 1 diabetes

et al. 2004

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“…The site of attack is organ-or tissue-specific: pancreatic ␤ cells in type 1 diabetes (3), myelin basic protein in multiple sclerosis (MS) 3 (4), thyroglobulin or thyroid peroxidase in thyroiditis (5), or more systemic: the synovial lining, lung, or heart in rheumatoid arthritis (RA) (6), or skin, kidney, or heart in systemic lupus erythematosus (SLE) (7). Despite these differences, clinically distinct autoimmune diseases exhibit common elements.…”

Section: 169: 5-9mentioning

confidence: 99%

Cutting Edge: Molecular Portrait of Human Autoimmune Disease

Maas

Chan

Parker

et al. 2002

The Journal of Immunology

189

167

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Autoimmune diseases affect 3–5% of the population, are mediated by the immune response to self-Ags, and are characterized by the site of tissue destruction. We compared expression levels of >4,000 genes in PBMC of control individuals before and after immunization to those of individuals with four distinct autoimmune diseases. The gene expression profile of the normal immune response exhibits coordinate changes in expression of genes with related functions over time. In contrast, each individual from all autoimmune diseases displays a similar gene expression profile unrelated to the pattern of the immunized group. To our surprise, genes with a distinct expression pattern in autoimmunity are not necessarily “immune response” genes, but are genes that encode proteins involved in apoptosis, cell cycle progression, cell differentiation, and cell migration.

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“…T-cell crossreactivity to ␤-cell autoantigens and unknown microbial epitopes has been proposed (29,30) as a molecular mechanism for the breakdown of immunologic tolerance and the subsequent appearance of T-cell autoreactivity. However, there are only limited examples of microbial agents linked to autoimmune pathogenicity (24,(31)(32)(33)(34)(35)(36).…”

Section: Discussionmentioning

confidence: 99%

Peptides From Common Viral and Bacterial Pathogens Can Efficiently Activate Diabetogenic T-Cells

et al. 2004

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Cross-reactivity between an autoantigen and unknown microbial epitopes has been proposed as a molecular mechanism involved in the development of insulin-dependent diabetes (type 1 diabetes). Type 1 diabetes is an autoimmune disease that occurs in humans and the nonobese diabetic (NOD) mouse. BDC2.5 is an isletspecific CD4؉ T-cell clone derived from the NOD mouse whose natural target antigen is unknown. A biometrical analysis of screening data from BDC2.5 T-cells and a positional scanning synthetic combinatorial library (PS-SCL) was used to analyze and rank all peptides in public viral and bacterial protein databases and identify potential molecular mimic sequences with predicted reactivity. Selected sequences were synthesized and tested for stimulatory activity with BDC2.5 T-cells. Active peptides were identified, and some of them were also able to stimulate spontaneously activated T-cells derived from young, pre-diabetic NOD mice, indicating that the reactivity of the BDC2.5 T-cell is directed at numerous mouse peptides. Our results provide evidence for their possible role as T-cell ligands involved in the activation of diabetogenic T-cells.

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Current cases in which epitope mimicry is considered as a component cause of autoimmune disease: immune-mediated (type 1) diabetes

Cited by 43 publications

References 60 publications

IgG4-subclass of glutamic acid decarboxylase antibody is more frequent in latent autoimmune diabetes in adults than in type 1 diabetes

IgG4-subclass of glutamic acid decarboxylase antibody is more frequent in latent autoimmune diabetes in adults than in type 1 diabetes

Cutting Edge: Molecular Portrait of Human Autoimmune Disease

Peptides From Common Viral and Bacterial Pathogens Can Efficiently Activate Diabetogenic T-Cells

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