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Autoantibodies to the presumptive cytoplasmic domain of platelet
glycoprotein IIIa in patients with chronic immune thrombocytopenic purpura
[published erratum appears in Blood 1991 Dec 1;78(11):3109]
K Fujisawa, TE O'Toole, P Tani, JC Loftus, EF Plow, MH Ginsberg and R McMillan
Department of Molecular and Experimental Medicine, Scripps Clinic and
Research Foundation, La Jolla, CA 92037.
Chronic immune thrombocytopenic purpura (ITP) is an autoimmune disorder due
to autoantibodies against platelets that result in their destruction. In
some patients, these autoantibodies bind to platelet glycoprotein (GP)
IIIa. With the aim of better defining the antigenic epitopes, plasma from
13 selected patients with chronic ITP known to have anti-GPIIb/IIIa
autoantibodies was tested for reactivity with nine synthetic peptides
corresponding to different regions of the GP IIIa molecule. Of these
plasmas, five bound significantly (P less than .001) with either peptide 8
(amino acids 721-744) or peptide 9 (amino acids 742-762), which together
form most of the carboxyterminal region presumed to be the cytoplasmic
domain. Three of these positive plasmas, were tested further. In two of
these positive plasmas, the anti-peptide antibodies represented greater
than 80% of the detectable circulating autoantibody. To further evaluate
the importance of the carboxyterminal region as an antigenic site, the
chronic ITP plasmas were tested against Chinese hamster ovary cells
transfected with GPIIb and either whole GPIIIa or GPIIIa lacking amino
acids 728 to 762. Ten of the 13 plasmas required the presence of this
region for significant autoantibody binding. We conclude that the
carboxyterminal region is an important area for stimulating antiplatelet
autoantibody formation in some patients with chronic ITP. It is not known
whether these autoantibodies to the presumed cytoplasmic domain play an
important role in the pathogenesis of the disease or occur as a secondary
phenomenon during the course of platelet destruction.
Volume 77,
Issue 10,
pp. 2207-2213,
05/15/1991
Copyright © 1991 by The American Society of Hematology
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