IMPORTANCE OF INTERFERON-GAMMA AND HLA-DR EXPRESSION IN AUTOIMMUNE THYROID-DISEASE

The purpose of this paper is to study some of the mechanisms by which antigen presentation, one of the first steps in the immune process, is modulated. Three different experiments are performed: a) Using thyroi d tissue from patients operated on for Graves'Disease, spontaneous HLA -DR and TPO antigen expressions were measured through the Citotoxicity Assay; these findings were correlated with the presence of antiTPO in the sera of these patients. It was found that only patients whose thy roid tissue spontaneously expressed both antigens had circulating anti TPO in their sera, thus demonstrating that dual expression is basic fo r antibody production. b) Blood samples from other Graves' patients we re obtained; peripheral lymphocytes were isolated and cultured in comp lete media for 5 days, then supernatant was separated and IFN-B concen tration was measured by a sandwich type RIA; the same procedure was do ne in 12 normal controls in order to compare the results. It was found that lymphocytes from Graves' patients secreted significantly more IF N-g than normal controls (20.9 +/- 13.54 U/ml vs 3.7 +/- 3.22 U/ml res pectively, p < 0.001) confirming that they were sensitized, so this de termination could be used as a marker of immune process, if other infe ctious conditions are excluded; also it was found that IFN-g hypersecr etion persists once hyperthyroidism has been treated, pointing out tha t the immune abnormality is still present. c) Finally, the capacity of reinducing HLA-DR antigen expression by IFN-g or other stimulators wa s studied in normal and Graves' thyrocytes by the citotoxicity assay: the response is dependant on the immunological condition of thyrocytes . in normal thyrocytes, reinduction of HLA-DR is higher than the one o btained in autoimmune thyrocytes: 23.9 +/- 6.48% vs 14.2 +/- 4.08% (p < 0.005), suggesting that in autoimmune diseases, receptors are occupi ed by other factors so they are not able to react to other stimuli Acc ording to. the present data, in Graves'Disease, previously sensitized lymphocytes hypersecrete IFN-g which perpetuates spontaneous HLA-DR ex pression and, if it is associated with the expression of other antigen s (TPO in our study, thus modulating specific antibody production by B lymphocytes. Reinduction of antigen expression in vitro is dependant on the underlying pathology.