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Humoral and Cellular Autoimmune Responses in Stiff Person Syndrome
aDepartment of Medicine I, University of Erlangen, 91054 Erlangen, Germany bKennedy Institute of Rheumatology, London W6 8LW, United Kingdom cSt. Bartholomew's Hospital, London EC1A 7BE, United Kingdom
Address for correspondence: Tobias Lohmann, Department of Medicine I, University of Erlangen, Ulmenweg 18, 91054 Erlangen, Germany. Voice: +49-9131-85-35229; fax: +49-9131-85-35231. tobias.lohmann{at}med1.imed.uni-erlangen.de Ann. N.Y. Acad. Sci. 998: 215-222 (2003).
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.
Key Words: stiff person syndrome • autoimmune disease • type 1 diabetes • glutamic acid decarboxylase 65 This article has been cited by other articles:
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