Humoral autoimmune responses to glutamic acid decarboxylase have similar target epitopes and subclass that show titer-dependent disease association.
Glutamic acid decarboxylase (GAD) is an autoantigen in stiff man syndrome (SMS) and type 1 diabetes (T1DM). Different GAD autoantibody characteristics in these disorders have suggested distinct underlying mechanisms of autoimmunity. Here, it is shown that increased prevalence of autoantibodies to GAD65 amino terminal and GAD67 epitopes and autoantibodies of IgG2, IgG3, or IgG4 subclass in patients with SMS (P < 0.001 vs. T1DM) are secondary to the markedly higher autoantibody titers in SMS patients (P < 0.0001) and that autoantibody epitopes and subclasses were similar when patients were matched for autoantibody titer. Exposure to autoantigen in the disorders is likely to involve similar humoral antigenic determinants, but different B cell regulation.
Piquer
Sandra
S
Immunology of Diabetes Unit, Istituto Scientifico San Raffaele, Milan, Italy.
Belloni
Cristina
C
Lampasona
Vito
V
Bazzigaluppi
Elena
E
Vianello
Marika
M
Giometto
Bruno
B
Bosi
Emanuele
E
Bottazzo
Gian Franco
GF
Bonifacio
Ezio
E
D000917:Antibody Formation; D000918:Antibody Specificity / Q000276:immunology; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000276:immunology*; D018985:Epitopes, B-Lymphocyte; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016750:Stiff-Person Syndrome / Q000150:complications / Q000276:immunology*
D001323:Autoantibodies; D018985:Epitopes, B-Lymphocyte; D005968:Glutamate Decarboxylase