Our objective was to ascertain the frequency of antibodies to glutamic acid decarboxylase (GAD) in Europids and four Asian ethnic groups with insulin-dependent diabetes mellitus (IDDM) to gain insight into why the prevalence and incidence of IDDM varies so widely among ethnic and/or geographically diverse population groups. The subjects in this study were Europid (n = 49), Japanese (n = 16), Thai (n = 7), Korean (n = 21), and Chinese (n = 13) persons with IDDM with a duration ranging from 5 to 14 years. There were similar numbers of healthy controls matched for each ethnic group. A validated radioimmunoprecipitation assay used GAD from pig brain radiolabeled with 125I using chloramine T. Islet cell cytoplasmic antibodies measured by indirect immunofluorescence were expressed as Juvenile Diabetes Foundation units. The prevalence of antibodies to GAD, compared with Europids (63%), was much lower in all Asian populations with IDDM: Japanese (31%), Thai (29%), Korean (5%), and Chinese (27%). The mean level of antibodies to GAD, however, among diabetics from each population who gave a positive reaction, was similar. For all groups, the prevalence of antibodies to GAD was much higher than that of islet cell cytoplasmic antibodies. Almost all IDDM subjects positive for islet cell antibodies had antibodies to GAD, but the converse did not hold. A radioimmunoprecipitation assay for antibodies to GAD applied to serum from subjects with IDDM in various ethnic groups showed that Europids with IDDM had a much higher prevalence of such antibodies than did Asians. This held for all ethnic groups, and particularly Koreans. Thus, among different populations, there may be etiologic heterogeneity of IDDM.(ABSTRACT TRUNCATED AT 250 WORDS)

Asian People↗

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The testicular biopsy: surgical procedure, fixation, and staining technics.

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Adult↗

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Hepatic portal infiltrates in mice immunized with syngeneic lymphoid cells: connotations for models of autoimmune liver disease.

The aim of this study was to investigate liver histology in mice after immunization with the conserved self molecule dihydrolipoamide dehydrogenase, E3, a subunit of the mitochondrial 2-OADC enzyme family identified as the M2 autoantigen in the liver disease, primary biliary cirrhosis. Mice were immunized by a novel procedure. The autoantigen E3 was introduced by pinocytosis into hypertonically treated syngeneic lymphoid cells to facilitate intracellular antigen processing and presentation and the generation of a cytolytic T cell response. Liver sections were examined and scored for evidence of an inflammatory response by two independent procedures: standard microscopy with visual scoring, and automated scanning with computerized scoring. There was a close correlation between read-outs of liver histology by standard microscopy and automated scanning, using the index of mononuclear cellular infiltrations in hepatic portal tracts. Such infiltrates were prominent in the immunized mice, but, unexpectedly, the degree of infiltration was similar in mice injected with autoantigen (E3)-loaded syngeneic cells, or syngeneic cells treated only with hypertonic medium. The equivalent changes in the liver with the experimental and control protocol is indicative of the reactivity of the liver to any provocative immune stimulus, and is cautionary for protocols designed for the induction of autoimmune liver disease in experimental animals.

Animals↗

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Type II collagen-immune complex arthritis in sheep: collagen antibodies in serum, synovial fluid and afferent lymph.

Type II native bovine collagen was used to induce arthritis in sheep. The sheep received a subcutaneous injection of collagen in Freund's adjuvant, and some sheep also received an intra-articular injection of collagen. The response to the collagen injections was monitored by measurement of antibody levels to bovine and ovine collagen in serum, synovial fluid and afferent lymph samples. There were antibodies in the normal sheep serum which reacted with native and denatured type II collagen, but there was a marked rise in serum and synovial fluid reactivity after subcutaneous injection of native collagen. In these sensitised sheep there was a further rise in antibody levels in the synovial fluid and afferent lymph samples after an intra-articular injection of collagen. There was little effect on antibody levels in the non-injected contralateral limb. Histological and immunohistochemical studies showed that the rise in antibody levels was associated with pathological changes to the synovium which were consistent with the development of arthritis. These changes were most severe in those joints of sensitized sheep which had received an intra-articular injection of collagen and were characterized by increased numbers of T cells in the synovial tissue, mainly of the CD4 phenotype. There was a marked increase in B cell expression by cells on the surface of the synovial intima, and accumulations of B and T cells were seen in the subsynovial tissues. Collagen-immune complex arthritis in sheep appears to be a useful large animal model of arthritis, with significant similarities to the arthropathies of other species, including man.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗