Characterization of CD4+ T cells specific for glutamic acid decarboxylase (GAD65) and proinsulin in a patient with stiff-person syndrome but without type 1 diabetes.
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.
Hänninen
Arno
A
Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland. arno.hanninen@utu.fi
Soilu-Hänninen
Merja
M
Hampe
Christiane S
CS
Deptula
Angie
A
Geubtner
Kelly
K
Ilonen
Jorma
J
Knip
Mikael
M
Reijonen
Helena
H
D000328:Adult; D001323:Autoantibodies / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology*; D006801:Humans; D011384:Proinsulin / Q000276:immunology*; D016750:Stiff-Person Syndrome / Q000150:complications / Q000276:immunology*
D001323:Autoantibodies; D011384:Proinsulin; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2