Humoral and cellular autoimmune responses in stiff person syndrome

Ann N Y Acad Sci. 2003 Sep;998:215-22. doi: 10.1196/annals.1254.024.


Stiff person syndrome (SPS) is a chronic autoimmune disease associated with humoral and cellular immune responses to glutamic acid decarboxylase (GAD) 65. Another chronic autoimmune disease, type 1 diabetes (T1D), is also associated with autoimmune responses to this antigen, but T1D patients develop SPS only extremely rarely and only a third of SPS patients develop T1D (mostly mild manifestations in adulthood). In a previous study, we described important differences between T1D and SPS in the autoimmune response to GAD 65: (1) T cells of SPS patients recognize epitopes in the middle of GAD 65 (amino residues 81-171 and 313-403), whereas patients with T1D preferentially recognize another middle (161-243) and a C-terminal region (473-555); and (2) GAD antibodies (Abs) were nearly exclusively of the Th1-associated IgG1 type in T1D, whereas SPS patients had both Th1- and Th2-associated IgG4 and IgE GAD Abs. These differences were not simply related to different HLA alleles. Fine epitope mapping revealed further distinct T cell epitopes in both diseases despite similar HLA background. Therefore, a single autoantigen can elicit different immune responses causing distinct chronic autoimmune diseases possibly related to a Th1 or Th2 bias of the disease.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibody Formation*
  • Antibody Specificity
  • Autoimmunity*
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / immunology
  • Female
  • Glutamate Decarboxylase / immunology*
  • Humans
  • Immunity, Cellular*
  • Immunodominant Epitopes / immunology
  • In Vitro Techniques
  • Isoenzymes / immunology*
  • Male
  • Middle Aged
  • Peptide Fragments / immunology
  • Stiff-Person Syndrome / complications
  • Stiff-Person Syndrome / diagnosis
  • Stiff-Person Syndrome / immunology*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism


  • Immunodominant Epitopes
  • Isoenzymes
  • Peptide Fragments
  • Glutamate Decarboxylase
  • glutamate decarboxylase 2