Review Article Immunogenetic Heterogeneity of Type 1 Diabetes in Japan

Type 1 diabetes is an organ-specific autoimmune disease characterized by T-cell mediated destruction of pancreatic ﾎｲ-cells . In Japanese population, the incidence of type 1 diabetes in children is very low compared to European countries. However, there are more patients with type 1 diabetes in adults, including latent autoimmune diabetes in adults (LADA). A variety of environmental and genetic factors are involved in the development of the disease. The human leukocyte antigen (HLA) class II genes (termed IDDM1) are the major genes associated with susceptibility to type 1 diabetes. HLA-DRB1*0405-DQB1*0401, HLA-DRB1* 0901-DQB1*0303 and HLA-DRB1*0802-DQB1*0302 are three major haplotypes in Japanese patients with type 1 diabetes. Other genetic factors reported in Japanese type 1 diabetes include the polymorphisms in insulin gene (IDDM2), CTLA-4 gene (IDDM12), MICA gene, Neuro D/Beta 2 gene, and IL-10 gene. The circulating autoantibodies to multiple islet autoantigens including GAD, insulin, and IA-2 are the important immunological features of type 1 diabetes. The prevalences of anti-islet autoantibodies in patients with Japanese type 1 diabetes are 60-70% for GAD autoantibodies, 45-50% for insulin autoantibodies (IAA), and 60-65% for IA-2 autoantibodies at disease onset, which are similar to those reported in Caucasian patients. With combinatorial analysis of these autoantibodies ninety percent of patients express at least one of these autoantibodies and are classified as immune-mediated type 1 diabetes. Although the majority of patients with type 1 diabetes are young, lean, and ketosisprone, there are number of patients with type 1 diabetes initially diagnosed as having type 2 diabetes at disease onset. These slow-onset diabetic patients with anti-islet autoantibodies often progress toward insulin-deficient state within several years after diagnosis. High level of GAD autoantibodies has a high predictive value for future insulin deficiency in slow-onset patients with type 1 diabetes. In conclusion, Japanese patients with type 1 diabetes are clinically heterogenous and the determination of immunological and genetic features are helpful to clarify the characteristics of the Japanese type 1 diabetic syndrome

Comparative frequency of four different types of pregnancy-associated thyrotoxicosis in a single thyroid centre

Abstract Background Pregnancy and delivery markedly influence thyroid function. However, the comparative prevalence of gestational thyrotoxicosis (GT), new onset of Graves’ disease during pregnancy (GD during pregnancy), postpartum destructive thyrotoxicosis (PPT), and postpartum Graves’ thyrotoxicosis (PPGD) has not yet been determined. Methods We prospectively registered and performed a review of 4127 consecutive non treated female patients with thyrotoxicosis, seen between August 2008 and December 2013 in our outpatient clinic of Kuma Hospital. 187 out of the 4127 women had new diagnosis of thyrotoxicosis during pregnancy or in the postpartum period. We investigated the prevalence of new diagnosis of GT, GD during pregnancy, PPT and PPGD and compared the characteristics of these types of thyrotoxicosis. The postpartum period is defined as twelve months after delivery. Results Out of 187 pregnant or postpartum women, we identified 30 (16.0%) with GT, 13 (7.0%) with GD during pregnancy, 42 (22.5%) with PPT, and 102 (54.5%) with PPGD. The onset time of thyrotoxicosis during pregnancy, i.e., both GT and GD during pregnancy, was delayed by a couple of weeks when hCG peaked at 10 gestational weeks. Seventy-six percent of patients with PPT developed thyrotoxicosis between delivery and 4 months postpartum; on the other hand, 83.3% of patients with PPGD developed thyrotoxicosis at 6 months postpartum or later. Conclusions We named gestational thyrotoxicosis, new onset of Graves’ disease during pregnancy, postpartum destructive thyrotoxicosis, and postpartum Graves’ thyrotoxicosis as pregnancy-associated thyrotoxicosis. A clinically significant number of women developed Graves’ disease in the postpartum period in a single thyroid centre

Investigation of oral macrolide prescriptions in Japan using a retrospective claims database, 2013–2018

Macrolide usage in Japan exceeds that in Europe and the United States. Investigating the actual conditions in which macrolides are used is important for identifying further interventions for appropriate antimicrobial use; however, this situation has not been evaluated in Japan. Therefore, we aimed to clarify the number of macrolide prescriptions and their changes before and after implementation of the Antimicrobial Resistance (AMR) Action Plan. In addition, we also investigated the names of diseases for which macrolides have been prescribed and the number of days of prescription. A retrospective observational study was conducted using JMDC claims data from January 2013 to December 2018. The proportion of all oral antimicrobials and macrolides used during this period and the diseases for which macrolides were used in the 3 years before and after the AMR Action Plan were determined separately for acute ( 14 prescription days) diseases. The number of prescriptions for macrolides constituted approximately 30% of those for all oral antimicrobials; of these, clarithromycin accounted for approximately 60%. Most prescriptions for acute diseases were for common cold, whereas allergic and dermatological diseases were included among chronic diseases. The names of these illnesses did not change before and after the AMR Action Plan. Overall, these results indicate that appropriate macrolide use involves a review of their use for common cold along with appropriate evaluation of their long-term use for skin and allergic diseases. They also indicate the need for further fact-finding studies and ongoing AMR measures

Antineutrophil Cytoplasmic Antibody-associated Vasculitis Complicating Graves\u27 Disease: Report of Two Adult Cases

Two adult female patients with established Graves\u27 disease were treated with propylthiouracil (PTU). One patient developed agranulocytosis, high fever of unknown origin and bilateral episcleritis. Another patient reported repeated attacks of common cold-like symptoms, polyarthralgia and skin purpura. There was no hematuria or proteinuria. Administration of PTU was withdrawn following identification of high myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) titer in the serum. Without steroids or immunosuppressive therapy, symptoms improved gradually in association with a fall in serum MPO-ANCA titer. We speculated that the symptoms of our two cases were due to MPO-ANCA associated vasculitis. MPO-ANCA positive vasculitis and glomerulonephritis are rare complications of PTU therapy, however, when these occur, the condition may become serious. Patients with Graves\u27 disease treated with PTU should be carefully observed during therapy

Genetic differentiation of Poly I:C from B:9-23 peptide induced experimental autoimmune diabetes

International audienceType 1 diabetes is an immune-mediated disease, in which T cells of the adaptive immune system mediate beta cell destruction. Recently the innate immune system has been linked to etiopathogenesis of several autoimmune diseases including type 1 diabetes, as innate effector cells (e.g. dendritic cells, monocytes/macrophages and NK cells) can prime and promote or regulate (auto)immune responses. We have previously developed an experimental autoimmune diabetes (EAD) model with insulin peptide B:9-23 immunization in transgenic H-2 d mice expressing the costimulatory molecule B7.1 in their islets (under the Rat Insulin Promotor, RIP). We compared the induction of diabetes with polyinosinic–polycytidylic acid (Poly I:C), a mimic of double stranded viral RNA versus insulin B:9-23 peptide in mice following backcrossing of the B7.1 transgene on to BALB/c mice from original B7.1 C57Bl/6 mice. We find that diabetes induction by Poly I:C is C57Bl/6 associated, whereas B:9-23 peptide induced diabetes and induction of insulin autoantibodies (IAA) are dependent on BALB/c genes. This B:9-23 peptide induced diabetes is consistent with MHC class II H-2 d being necessary for the response to this peptide. Of note Poly I:C induction of diabetes was lost while B:9-23 induction was retained with backcrossing to BALB/c mice. Interaction of genes and environment (antigenic epitope and viral mimic) can be important in the pathogenesis of immune mediated diabetes and activation of the innate immune system (e.g. Poly I:C) may be one key determinant