Humoral and cellular immune parameters before and during immunosuppressive therapy of a patient with stiff-man syndrome and insulin dependent diabetes mellitus
- M Hummela,
- I Durinovic-Belloa,
- E Bonifaciob,
- V Lampasonab,
- J Endlc,
- S Fesselec,
- F Then Berghd,
- C Trenkwalderd,
- E Standla,
- A-G Zieglera
- aDiabetes Research Institute and 3rd Medical Department, Academic City Hospital München-Schwabing, Munich, Germany, bInstitutio Scientifico San Raffaele, Milan, Italy, cBoehringer Mannheim Research Center, Penzberg, Germany, dMax-Planck Institute for Psychiatry, Munich, Germany
- Dr Anette-G Ziegler, Diabetes Research Institute, Kölner Platz 1, 80804 Munich, Germany. Telephone 089–30 79 31 21; fax 089–3 08 17 33; emailanziegler{at}lrz.uni-muenchen.de
- Received 23 September 1997
- Revised 27 November 1997
- Accepted 23 December 1997
Abstract
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.
