Autoimmunity
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Islet cell antigens have been administered orally and intravenously (I. V.) to NOD mice to assess their abilities to protect from or delay the onset of diabetes, and thereby provide insights that may have therapeutic implications in human trials. Whereas we and others have observed a delay in the onset of diabetes in NOD mice that have been fed with insulin from early life, we report here for the first time that feedings with porcine GAD65 alone (p = 0.226) or in combination with insulin (p = 0.011), have anti-diabetic effects in a prolonged study period (>400 days). ⋯ V. human recombinant GAD65, and porcine GAD given at weaning, delayed diabetes onset (p = 0.004) while similar treatments with a variety of inactive insulin preparations were generally ineffective. These findings thus indicate varying effects of oral and I. V. autoantigen administrations on the development of diabetes in NOD mice, and describe the immunological processes induced by oral autoantigen treatments.
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Comparative Study
Induction of microsomal antigen and comparison with histologic localization of HLA-DR in Graves' thyroid tissue.
We have characterized thyroid microsomal antigen (M-Ag) prepared from Graves' and normal thyroid tissues using 100,000 x g thyroid membrane fractions in enzyme-linked immunosorbent assays with pooled polyclonal human sera containing high titers of antibody to M-Ag. A ten-fold parallel increase in dose inhibition potencies occurred with M-Ag preparations from Graves' as compared to normal thyroid tissue. The M-Ag preparations were further evaluated by SDS-polyacrylamide gel electrophoresis and proteins visualized by Western blot using high titer microsomal antibody (M-Ab) sera (n = 2) devoid of thyroglobulin antibody activity. ⋯ This was in contrast to follicular cell staining for HLA-DR antigen which was present in 6 of 10 Graves' tissues examined and absent in normal thyroid tissue. Staining for HLA-DR antigen also occurred on the follicular cell surface membrane with occasional enhancement at the thyrocyte apical cell membrane. We conclude: a) M-Ag is induced approximately 10-fold in Graves' thyroid tissue and can be objectively quantified in ELISA systems, 2) There were no detectable qualitative differences between M-Ag from Graves' and normal thyroid tissue, and 3) HLA-DR antigen was detected on 60% Graves' tissues in a cell surface distribution similar to that observed for M-Ag in both Graves' and normal tissues.