Humoral and cellular immune parameters before and during immunosuppressive therapy of a patient with stiff-man syndrome and insulin dependent diabetes mellitus.
OBJECTIVE
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-gamma) 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-gamma production after stimulation with GAD or IA-2 suggesting increased activation of TH1 cells.


CONCLUSIONS
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.
Hummel
M
M
Diabetes Research Institute and 3rd Medical Department, Academic City Hospital, München-Schwabing, Munich, Germany.
Durinovic-Bello
I
I
Bonifacio
E
E
Lampasona
V
V
Endl
J
J
Fessele
S
S
Then Bergh
F
F
Trenkwalder
C
C
Standl
E
E
Ziegler
A G
AG
D001323:Autoantibodies / Q000097:blood*; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000276:immunology*; D003929:Diabetic Neuropathies / Q000188:drug therapy / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D000939:Epitopes / Q000276:immunology; D005968:Glutamate Decarboxylase / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000097:blood; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009460:Neurologic Examination / Q000187:drug effects; D011239:Prednisolone / Q000627:therapeutic use*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000276:immunology; D016750:Stiff-Person Syndrome / Q000188:drug therapy / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D001323:Autoantibodies; D000939:Epitopes; D007166:Immunosuppressive Agents; D007371:Interferon-gamma; D011239:Prednisolone; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; D005968:Glutamate Decarboxylase