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Spectrum of Ig classes, specificities, and titers of serum
antiglycoproteins in chronic idiopathic thrombocytopenic purpura
R He, DM Reid, CE Jones and NR Shulman
Clinical Hematology Branch, National Institute of Diabetes and Digestive
and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.
The characteristic decreased recovery and survival of transfused platelets
in nonalloimmunized patients with idiopathic thrombocytopenic purpura (ITP)
suggest that plasma antiplatelet autoantibodies (autoAbs) are present in
almost all cases. Studies emphasizing reactions of IgG autoAbs with
platelet glycoprotein (GP) IIb/IIIa indicate that less than 50% of ITP
patients have detectable serum Abs, and that many of these Abs may not be
pathogenic because they are directed against epitopes in the cytoplasmic
domain of GPIIIa (Fujisawa et al, Blood 77:2207, 1991 and 79:1441, 1992).
We evaluated the contribution of Ig classes other than IgG to the overall
incidence of serum Abs in 47 patients with chronic ITP and the frequency of
reactions with GPs IIb/IIIa, Ib/IX, IV, and Ia/IIa. Abs were further
characterized by their reactions with cytosolic or exosolic GP epitopes and
their titers and apparent affinities. Using immunobead techniques we found
(1) anti- GPs in 85% of sera; (2) IgA and IgG Abs each in 68%, together in
51%; (3) IgM agglutinins in 15%, always with another Ab class; (4) GP
Ib/IX, IIb/IIIa, IV, and Ia/IIa targets in 83%, 81%, 38%, and 28% of cases,
respectively; (5) 93% of positive sera reactive with more than one GP; but
GP IV or Ia/IIa never the sole target; (6) Abs against cytosolic epitopes
on one or more of GPs IIIa, Ib alpha, and IIb beta in 66% of sera, always
accompanied by Abs against exosolic epitopes of the same or a different GP;
(7) autoAbs against cytosolic GP epitopes in 38% of 16 patients recovered
from posttransfusion purpura and drug purpura; and (8) evidence that serum
ITP Abs, often high-titered, saturate platelets less than alloAbs against
the same GPs. Whereas Abs against external GP epitopes are a distinctive
marker for ITP in 80% of patients, Abs against internal GP epitopes are
likely a secondary phenomenon of platelet destruction and not pathogenic.
Anti-GPs against exosolic epitopes were also found in eluates of patient's
platelets, suggesting that they have pathogenic significance.
Volume 83,
Issue 4,
pp. 1024-1032,
02/15/1994
Copyright © 1994 by The American Society of Hematology
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