Humoral and cellular autoimmune responses in stiff person syndrome.
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.
Lohmann
Tobias
T
Department of Medicine I, University of Erlangen, 91054 Erlangen, Germany. tobias.lohmann@med1.imed.uni-erlangen.de
Londei
Marco
M
Hawa
Mohammed
M
Leslie
R David G
RD
D000293:Adolescent; D000328:Adult; D000368:Aged; D000917:Antibody Formation; D000918:Antibody Specificity; D015551:Autoimmunity; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000276:immunology; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D016056:Immunodominant Epitopes / Q000276:immunology; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000276:immunology; D016750:Stiff-Person Syndrome / Q000150:complications / Q000175:diagnosis / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D016056:Immunodominant Epitopes; D007527:Isoenzymes; D010446:Peptide Fragments; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2