Circulating immune complexes (ClC) were detected by platelet aggregation test (PAT) in 40.0% of 45 diabetics and by polyethylene glycol precipitation-complement consumption test (PEG-CC test) in 30.6% of 36 diabetics as compared to 5% and 10% of 20 normal control subjects for each test. The prevalence of CIC in diabetics was significantly higher than in the normal controls (P < 0.05%). There were no correlations between the presence of ClC detected by PAT and the duration of the disease, insulin treatment, or diabetic complications. Thus multiple factors must contribute to the increase of ClC in diabetics. The role of these various factors needs to be studied.
Antigen-Antibody Complex/metabolism* ; Diabetes Mellitus/complications ; Diabetes Mellitus/immunology* ; Diabetes Mellitus, Insulin-Dependent/drug therapy ; Diabetes Mellitus, Insulin-Dependent/immunology ; Diabetes Mellitus, Non-Insulin-Dependent/immunology ; Human ; Insulin/therapeutic use ; Platelet Aggregation ; Time Factors

BACKGROUND: Type 1 diabetes mellitus is frequently associated with other autoimmune diseases. The occurrence of common features of autoimmune diseases and the coassociation of multiple autoimmune diseases in the same individual or family supports the notion that there may be common genetic factors. METHODS: To investigate potential clustering of autoimmune thyroid disease (ATD) among type 1 diabetes patients and the contribution of common susceptibility genes to this, HLA DR/DQ alleles as well as antithyroid autoantibodies were measured in 115 Korean patients with type 1 diabetes and their 96 first-degree family members. RESULTS: Twenty-five percent of the patients had ATD, whereas 3 of 36 (8%) age-matched normal controls had ATD (RR = 3.7, p < 0.05). Twenty-six of ninty-six (27%) type 1 diabetes family members had ATD. No differences in the distribution of HLA alleles/haplotypes and genotypes between the patients with and without ATD were found. CONCLUSION: From this finding, we could assess that individuals with type 1 diabetes and their relatives frequently develop ATD, perhaps due to common susceptibility genes that are shared among first degree relatives.
Adult ; Alleles ; Autoantibodies/blood ; Autoimmune Diseases/epidemiology* ; Child ; Child, Preschool ; Diabetes Mellitus, Insulin-Dependent/genetics ; Diabetes Mellitus, Insulin-Dependent/complications* ; Female ; Glutamate Decarboxylase/immunology ; HLA-DQ Antigens/genetics ; HLA-DR Antigens/genetics ; Human ; Male ; Prevalence ; Thyroid Diseases/epidemiology*

To investigate whether BCG, lymphtoxin (LT) or bee venom (BV) can prevent insulitis and development of diabetes in non-obese diabetic (NOD) mice, we measured the degree of insulitis and incidence of diabetes in 24 ICR and 96 female NOD mice. NOD mice were randomly assigned to control, BCG-, LT-, and BV-treated groups. The BCG was given once at 6 weeks of age, and LT was given in 3 weekly doses from the age of 4 to 10 weeks. The BV was injected in 2 weekly doses from the age of 4 to 10 weeks. Diabetes started in control group at 18 weeks of age, in BCG group at 24 weeks of age, and in LT- or BV-treated group at 23 weeks of age. Cumulative incidences of diabetes at 25 weeks of age in control, BCG-, LT-, and BV-treated NOD mice are 58, 17, 25, and 21%, respectively. Incidence and severity of insulitis were reduced by BCG, LT and BV treatment. In conclusion, these results suggest that BCG, LT or BV treatment in NOD mice at early age inhibit insulitis, onset and cumulative incidence of diabetes.
Adjuvants, Immunologic/pharmacology* ; Age Factors ; Animal ; Bee Venoms/pharmacology* ; Cholesterol/blood ; Diabetes Mellitus/prevention & control* ; Diabetes Mellitus/immunology ; Diabetes Mellitus, Insulin-Dependent/prevention & control* ; Diabetes Mellitus, Insulin-Dependent/immunology ; Disease Models, Animal ; Female ; Islets of Langerhans/pathology* ; Islets of Langerhans/drug effects ; Lymphotoxin/pharmacology* ; Mice ; Mice, Inbred NOD ; Mycobacterium bovis/immunology* ; Triglycerides/blood

Due to their high immunostimulatory ability as well as the critical role they play in the maintenance of self-tolerance, dendritic cells have been implicated in the pathogenesis of autoimmune diseases. The non-obese diabetic (NOD) mouse is an animal model of autoimmune type 1 diabetes, in which pancreatic beta cells are selectively destroyed mainly by T cell-mediated immune responses. To elucidate initiation mechanisms of beta cell-specific autoimmunity, we attempted to generate bone marrow-derived dendritic cells from NOD mice. However, our results showed low proliferative response of NOD bone marrow cells and some defects in the differentiation into the myeloid dendritic cells. NOD dendritic cells showed lower expressions of MHC class II, B7-1, B7-2 and CD40, compared with C57BL/6 dendritic cells. In mixed lymphocyte reactions, stimulatory activities of NOD dendritic cells were also weak. Treatment with LPS, INF-gamma and anti-CD40 stimulated NOD dendritic cells to produce IL-12p70. The amount of IL-12, however, appeared to be lower than that of C57BL/6. Results of the present study indicated that there may be some defects in the development of NOD dendritic cells in the bone marrow, which might have an impact on the breakdown of self tolerance.
Animal ; Autoimmune Diseases/pathology ; Autoimmune Diseases/immunology ; Bone Marrow Cells/pathology* ; Bone Marrow Cells/immunology* ; Bone Marrow Cells/chemistry ; Cell Differentiation/immunology ; Cell Differentiation/drug effects ; Dendritic Cells/pathology* ; Dendritic Cells/immunology* ; Dendritic Cells/chemistry ; Diabetes Mellitus, Insulin-Dependent/pathology* ; Diabetes Mellitus, Insulin-Dependent/immunology ; Enzyme-Linked Immunosorbent Assay ; Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology ; Interleukin-12/analysis ; Interleukin-4/pharmacology ; Lipopolysaccharides/pharmacology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Inbred NOD ; Obesity