The lack of anti-idiotypic antibodies, not the presence of the corresponding autoantibodies to glutamate decarboxylase, defines type 1 diabetes.
Autoantibodies to glutamate decarboxylase 65 (GAD65Ab) are commonly believed to be a major characteristic for type 1 diabetes (T1D). We investigated the presence of GAD65Ab in healthy individuals (n = 238) and first-degree relatives (FDRs) of T1D patients (n = 27) who tested negative for GAD65Ab in conventional RIAs. Sera were applied to affinity columns coated with GAD65-specific mAbs to absorb anti-idiotypic antibodies (anti-Ids). The absorbed sera were analyzed for binding to GAD65 by RIAs. Both healthy individuals and FDRs present GAD65Ab that are inhibited by anti-Id, masking them in conventional detection methods. The presence of GAD65Ab-specific anti-Ids was confirmed by competitive ELISA. Remarkably, T1D patients (n = 54) and Stiff Person Syndrome patients (n = 8) show a specific lack of anti-Ids to disease-associated GAD65Ab epitopes. Purified anti-Ids from healthy individuals and FDRs inhibited the binding of GAD65Ab from T1D patients to GAD65. We conclude that masked GAD65Ab are present in the healthy population and that a lack of particular anti-Ids, rather than GAD65Ab per se, is a characteristic of T1D. The lack of these inhibitory antibodies may contribute to T cell activation by GAD65Ab.
Oak
Shilpa
S
Department of Medicine, University of Washington, HSB-165, 1959 Pacific Street NE, Seattle, WA 98195, USA.
Gilliam
Lisa K
LK
Landin-Olsson
Mona
M
Törn
Carina
C
Kockum
Ingrid
I
Pennington
Christina R
CR
Rowley
Merrill J
MJ
Christie
Michael R
MR
Banga
J Paul
JP
Hampe
Christiane S
CS
D000888:Antibodies, Anti-Idiotypic / Q000097:blood*; D001323:Autoantibodies / Q000097:blood*; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000175:diagnosis* / Q000276:immunology*; D005192:Family Health; D005968:Glutamate Decarboxylase / Q000276:immunology*; D006801:Humans; D011863:Radioimmunoassay; D016750:Stiff-Person Syndrome
D000888:Antibodies, Anti-Idiotypic; D001323:Autoantibodies; D005968:Glutamate Decarboxylase