Humoral and cellular immune parameters before and during immunosuppressive therapy of a patient with stiff-man syndrome and insulin dependent diabetes mellitus

• Published in: Journal of neurology, neurosurgery and psychiatry neurosurgery and psychiatry, 1998-08, Vol.65 (2), p.204-208
• Main Authors: Hummel, M, Durinovic-Bello, I, Bonifacio, E, Lampasona, V, Endl, J, Fessele, S, Bergh, F Then, Trenkwalder, C, Standl, E, Ziegler, A-G
• Format: Article
• Language: English
• Subjects: Antibodies; autoantibodies; Autoantibodies - blood; Autoimmune Diseases - drug therapy; Autoimmune Diseases - immunology; Biological and medical sciences; Cell growth; Cytokines; Diabetes; Diabetes Mellitus, Type 1 - drug therapy; Diabetes Mellitus, Type 1 - immunology; Diabetic Neuropathies - drug therapy; Diabetic Neuropathies - immunology; Dose-Response Relationship, Drug; Drug Administration Schedule; Epitopes - immunology; Glucose; Glutamate Decarboxylase - immunology; Humans; Immunomodulators; Immunosuppressive Agents - therapeutic use; Insulin; Interferon-gamma - blood; Lymphocyte Activation - drug effects; Lymphocyte Activation - immunology; Lymphocytes; Male; Medical sciences; Middle Aged; Neurologic Examination - drug effects; Oral administration; Patients; Pharmacology. Drug treatments; Prednisolone - therapeutic use; prednisolone therapy; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Protein Tyrosine Phosphatases - immunology; Proteins; stiff-man syndrome; Stiff-Person Syndrome - drug therapy; Stiff-Person Syndrome - immunology; T cell reactivity; T-Lymphocytes - drug effects; T-Lymphocytes - immunology
• ISSN: 0022-3050; 1468-330X
• DOI: 10.1136/jnnp.65.2.204

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 TH1 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.