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 type of stiff-man syndrome and insulin dependent diabetes (IDDM). Methods Antibodies and T cell proliferation against GAD and IA-2 and cytokine release of antigen stimulated T cells (IFN-γ) were determined before and several times during immunosuppressive therapy with prednisolone. Results Raised GAD antibodies against full length GAD65 or chimeric 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 responses to both GAD and IA-2 were seen before therapy and once on reduction of high cortisone dosages when the patient showed signs of clinical deterioration. Cytokine profiles showed increased IFN-γ production after stimulation with GAD or IA-2 suggesting increased activation of T _H1 cells. Conclusion Immunosuppressive therapy --even with extremely high doses of 500 mg a day--does not lead to the reduction of antibody concentrations in the periphery nor to a switch in epitope recognition of such antibodies despite clinical improvement. The amount of T cell reactivity to various antigens, however, may be a useful marker to monitor the effectiveness of immunotherapy.