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Stuart Baker, Ricardo Núñez Miguel, Daniel Thomas, Michael Powell, Jadwiga Furmaniak, and Bernard Rees Smith

. ( ) Godlewska M Czarnocka B Gora M 2012 Localization of key amino acid residues in the dominant conformational epitopes on thyroid peroxidase recognized by mouse monoclonal antibodies . Autoimmunity 45 476

Open access

Ricardo Núñez Miguel, Paul Sanders, Lloyd Allen, Michele Evans, Matthew Holly, William Johnson, Andrew Sullivan, Jane Sanders, Jadwiga Furmaniak, and Bernard Rees Smith

receptor with TSH antagonist activity . Auto-Immunity Highlights 10 11. ( ) Furmaniak J Sanders J Sanders P Li Y Rees Smith B 2022 TSH receptor specific monoclonal autoantibody K1-70™ targeting of the

Free access

WM Kuhtreiber, T Hayashi, EA Dale, and DL Faustman

Lymphocyte development, selection and education represent tightly controlled immune processes that normally prevent autoimmunity. Lymphocyte development likely induces cellular selection through apoptosis to remove potentially autoreactive cells. Dysregulated apoptosis, both interrupted as well as accelerated apoptosis, are now demonstrated as central defects in diverse murine autoimmune disease. In murine models of autoimmune lupus, mutations in cell death receptor Fas (CD95) and its ligand, FasL (CD95 L), have been identified. These errors create a lymphoid system resistant to apoptosis. In contrast, select lymphoid subpopulations of maturing autoimmune prone non-obese diabetic mice have identifiable and pathogenic T cells with both in vivo and in vitro heightened apoptosis after drug interventions. In part, these defects are due to faulty activation of transcription factors such as nuclear factor-kappaB (NF-kappaB) that normally protect against apoptotic death. The genetic basis of interrupted NF-kappaB in pathogenic memory T cells in diabetes is attributable to a developmentally controlled gene defect in an essential subunit of the proteasome. No specific gene in most common forms of human autoimmune disease has yet been identified. Functional assays from diverse laboratories repeatedly demonstrate heightened apoptosis in multiple cellular signaling pathways for cell death, suggesting a common theme in disease causality.

Free access

Zodwa Dlamini, Fortunate Mokoena, and Rodney Hull

Diabetes mellitus (DM) is a non-communicable, metabolic disorder that affects 416 million individuals worldwide. Type 2 diabetes contributes to a vast 85–90% of the diabetes incidences while 10–15% of patients suffer from type 1 diabetes. These two predominant forms of DM cause a significant loss of functional pancreatic β-cell mass causing different degrees of insulin deficiency, most likely, due to increased β-cell apoptosis. Treatment options involve the use of insulin sensitisers, α-glucosidase inhibitors, and β-cell secretagogues which are often expensive, limited in efficacy and carry detrimental adverse effects. Cost-effective options for treatment exists in the form of herbal drugs, however, scientific validations of these widely used medicinal plants are still underway. Alternative splicing (AS) is a co-ordinated post-transcriptional process in which a single gene generates multiple mRNA transcripts which results in increased amounts of functionally different protein isoforms and in some cases aberrant splicing leads to metabolic disease. In this review, we explore the association of AS with metabolic alterations in DM and the biological significance of the abnormal splicing of some pathogenic diabetes-related genes. An understanding of the molecular mechanism behind abnormally spliced transcripts will aid in the development of new diagnostic, prognostic and therapeutic tools.

Free access

Heather C Denroche and C Bruce Verchere

differently in the presence of beta cell dysfunction in early autoimmunity. Indeed, we recently reported disproportionately elevated levels of the proIAPP processing intermediate hproIAPP 1–48 in T1D ( Courtade et al . 2017 a ) suggesting that, along with

Free access

DA Chistiakov and RI Turakulov

Autoimmune thyroid disease (AITD) occurs in two common forms: Graves' disease and Hashimoto thyroiditis. On the basis of functional and experimental data, it has been suggested that the gene encoding cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) is a candidate gene for conferring susceptibility to thyroid autoimmunity. In this review, we critically evaluate the evidence for pathogenetic involvement of CTLA-4 in the various forms of AITD and focus on the possible role of genetic variation of the CTLA4 locus. Population genetics data strongly suggest a role for the CTLA4 region in susceptibility to AITD. However, further functional studies are required to understand the significance of CTLA4 polymorphisms in the pathogenic mechanism of AITD.

Free access

Francesco Maria Egro

contrasting ideas have been brought forward in the literature to explain this rapid increase in the incidence of type 1 diabetes. A variety of hypotheses try to explain this lability in the immune system, which leads to autoimmunity of the pancreatic β

Free access

Catherine J Owen, James A Eden, Claire E Jennings, Valerie Wilson, Tim D Cheetham, and Simon H S Pearce

Introduction Autoimmune endocrinopathies, including Graves’ disease (GD) and autoimmune Addison’s disease (AAD), are the commonest type of autoimmunity in Western populations. However, their pathogenesis remains poorly defined. Like

Free access

Ehsan Razmara, Mehrnaz Salehi, Saeed Aslani, Amirreza Bitaraf, Hassan Yousefi, Jonathan Rosario Colón, and Mahdi Mahmoudi

autoimmune diseases ( Devarajan 2014 ) ( Fig. 3A ). Indeed, activating heterozygote mutations in CTLA4 increased the rate of autoimmunity, while treating with anti-CTLA4 monoclonal antibodies suppressed T cell activation and reduced the incidence of AITDs

Free access

C E Jennings, C J Owen, V Wilson, and S H S Pearce

,25-dihydroxyvitamin D 3 (1,25(OH) 2 -D 3 ), the biologically active form of vitamin D, has been shown to ameliorate murine autoimmunity in the nonobese diabetic (NOD) model ( Mathieu et al. 1992 ) and in experimental autoimmune encephalomyelitis, a model of