HUMORAL AND CELLULAR IMMUNE PARAMETERS BEFORE AND DURING IMMUNOSUPPRESSIVE THERAPY OF A PATIENT WITH STIFF-MAN SYNDROME AND INSULIN-DEPENDENT DIABETES-MELLITUS

Objectives-Humoral and cellular immune reactivity are reported for two neuroendocrine autoantigens-glutamic acid decarboxylase (GAD) and the protein tyrosine phosphatase IA-2-in a patient with the autoimmune ty pe of stiff-man syndrome and insulin dependent diabetes (IDDM). Method s-Antibodies and T cell proliferation against GAD and IA-2 and cytokin e release of antigen stimulated T cells (IFN-gamma) were determined be fore and several times during immunosuppressive therapy with prednisol one. Results-Raised GAD antibodies against full length GAD65 or chimer ic constructs were detected before therapy and they remained at a high concentration despite a marked clinical improvement during cortisone treatment. Antibodies to IA-2 were undetectable, but weak T cell respo nses to both GAD and IA-2 were seen before therapy and once on reducti on of high cortisone dosages when the patient showed signs of clinical deterioration. Cytokine profiles showed increased IFN-gamma productio n after stimulation with GAD or IA-2 suggesting increased activation o f T(H)1 cells. Conclusion-Immunosuppressive therapy -even with extreme ly high doses of 500 mg a day-does not lead to the reduction of antibo dy concentrations in the periphery nor to a switch in epitope recognit ion of such antibodies despite clinical improvement. The amount of T c ell reactivity to various antigens, however, may be a useful marker to monitor the effectiveness of immunotherapy.