Prevention of type 1 diabetes mellitus using a novel vaccine

Abstract

Type 1 diabetes mellitus (T1DM) affects 1 in 300 people and the incidence of the disease is rising worldwide. T1DM is caused by chronic autoimmune destruction of the insulin-producing β-cells. The exact etiology and primary auto-antigen are not yet known. The autoimmune, chronic, and progressive nature of the disease raises the possibility of intervention, preferably by slowing down or stopping the destruction of the β-cells as early as the prediabetic stage. Since the 1980s, several attempts have been made to maintain β-cell function using immunosuppressive agents, immune modulation such as plasmapheresis, cytokine therapy, or antibody treatment. These agents were not diabetes specific; the occasionally observed beneficial effect did not compensate for the often very severe side effects. According to the latest assumption, the administration of diabetes-specific auto-antigens can elicit tolerance, which can prevent the destruction of the β-cells, hopefully without serious side effects. The authors summarize current understanding of the immunology of T1DM, review the trials on prevention, and discuss their vaccination study.

The Role of MIF in Type 1 and Type 2 Diabetes Mellitus

“…T1DM is the result of the autoimmune destruction of pancreatic islet β cells by infiltrating immune cells (insulitis); this occurs due to a failure in immune tolerance because the organism has had contact with specific viruses [ 33 ] such as cytomegalovirus [ 34 ] or with food molecules that caused molecular mimicry [ 35 ]. The common autoantigens recognized in this disease are insulin, glutamate decarboxylase 65 (GAD65), and the islet antigens IA-2 and IA-2 β [ 36 , 37 ]. During insulitis, high levels of proinflammatory cytokines, including IL-1 β , TNF α , IL-12, MIF, and IFN γ , are secreted by effector T cells to trigger the β cell destruction process [ 32 ].…”

The elusive role of B lymphocytes and islet autoantibodies in (human) type 1 diabetes

“…Immunotherapies targeting (auto)antibodies, such as plasmapheresis and intravenous immunoglobulin replacement (IVIG), as a primary treatment for type 1 diabetes, have had negligible effects on disease [31,32]. Autoantibody titres rarely correlate with clinical remission in immune intervention studies, suggesting that islet autoantibodies play a minor role, at best, in relapse or remission of type 1 diabetes [33].…”

Monocyte chemoattractant protein 1 and macrophage migration inhibitory factor in children with type 1 diabetes

“…It is the result of the autoimmune destruction of pancreatic islet β cells (insulitis); this occurs due to a failure in immune tolerance because the organism has had contact with specific viruses or with food molecules that caused molecular mimicry [3]. The common autoantigens recognized T1DM are insulin, glutamate decarboxylase 65 (GAD65), and the islet antigens IA-2 and IA-2β [4,5]. During insulitis, high levels of pro-inflammatory cytokines, including, MIF are secreted by effector T cells to trigger the β cell destruction process [1].…”