BACKGROUND: Glutamic acid decarboxylase (GAD) is a rate-limiting enzyme in the synthesis of gamma-amino butyric acid (GABA) and an important autoantigen both in patients with type 1 diabetes (T1D) and stiff-person syndrome (SPS). Autoantibodies (GADA) to the 65-kDa isoform of GAD are a characteristic feature in both diseases. Approximately 30% of patients with SPS develop diabetes, yet, it is unclear to which extent co-existing autoimmunity to GAD65 and other islet autoantigens determines the risk of developing T1D. METHODS: In this study, we monitored CD4+ T-cell responses to GAD65 and proinsulin in a patient with SPS who remained normoglycaemic during the 46-month follow-up. RESULTS: Fluctuating but persistent T-cell reactivity to GAD65 was identified, as well as T-cell reactivity to proinsulin at one time point. The majority of the T-cell clones isolated from the patient with SPS produced high levels of Th2 cytokines (IL-13, IL-5 and IL-4). We also examined levels of GADA, insulin and IA-2 autoantibodies, and epitope specificity of GADA. In both serum and cerebrospinal fluid (CSF), GADA levels were high, and GADA persisted throughout the follow-up. Despite T-cell reactivity to both GAD65 and proinsulin, autoantibodies to other islet autoantigens did not develop. CONCLUSIONS: Further follow-up will determine whether the beta-cell autoimmunity observed in this patient will eventually lead to T1D.
BACKGROUND:Glutamic acid decarboxylase (GAD) is a rate-limiting enzyme in the synthesis of gamma-amino butyric acid (GABA) and an important autoantigen both in patients with type 1 diabetes (T1D) and stiff-person syndrome (SPS). Autoantibodies (GADA) to the 65-kDa isoform of GAD are a characteristic feature in both diseases. Approximately 30% of patients with SPS develop diabetes, yet, it is unclear to which extent co-existing autoimmunity to GAD65 and other islet autoantigens determines the risk of developing T1D. METHODS: In this study, we monitored CD4+ T-cell responses to GAD65 and proinsulin in a patient with SPS who remained normoglycaemic during the 46-month follow-up. RESULTS: Fluctuating but persistent T-cell reactivity to GAD65 was identified, as well as T-cell reactivity to proinsulin at one time point. The majority of the T-cell clones isolated from the patient with SPS produced high levels of Th2 cytokines (IL-13, IL-5 and IL-4). We also examined levels of GADA, insulin and IA-2 autoantibodies, and epitope specificity of GADA. In both serum and cerebrospinal fluid (CSF), GADA levels were high, and GADA persisted throughout the follow-up. Despite T-cell reactivity to both GAD65 and proinsulin, autoantibodies to other islet autoantigens did not develop. CONCLUSIONS: Further follow-up will determine whether the beta-cell autoimmunity observed in this patient will eventually lead to T1D.
Authors: C S Hampe; L P Hammerle; L Bekris; E Ortqvist; I Kockum; O Rolandsson; M Landin-Olsson; C Törn; B Persson; A Lernmark Journal: J Clin Endocrinol Metab Date: 2000-12 Impact factor: 5.958
Authors: Gustavo Fenalti; Ruby H P Law; Ashley M Buckle; Christopher Langendorf; Kellie Tuck; Carlos J Rosado; Noel G Faux; Khalid Mahmood; Christiane S Hampe; J Paul Banga; Matthew Wilce; Jason Schmidberger; Jamie Rossjohn; Ossama El-Kabbani; Robert N Pike; A Ian Smith; Ian R Mackay; Merrill J Rowley; James C Whisstock Journal: Nat Struct Mol Biol Date: 2007-03-25 Impact factor: 15.369
Authors: M Costa; A Saiz; R Casamitjana; M Fernández Castañer; A Sanmartí; F Graus; D Jaraquemada Journal: Clin Exp Immunol Date: 2002-09 Impact factor: 4.330