REACTIVITY OF AUTOANTIBODIES FROM CHRONIC ITP PATIENTS WITH RECOMBINANT GLYCOPROTEIN IIIA PEPTIDES

被引:17
作者
BOWDITCH, RD [1 ]
TANI, P [1 ]
MCMILLAN, R [1 ]
机构
[1] SCRIPPS RES INST, DEPT MOLEC & EXPTL MED, LA JOLLA, CA 92037 USA
关键词
AUTOANTIBODY; PLATELETS; IMMUNE THROMBOCYTOPENIA; EPITOPES; RECOMBINANTS;
D O I
10.1111/j.1365-2141.1995.tb05266.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Chronic immune thrombocytopenia is an autoimmune disorder characterized by destructive thrombocytopenia due to the formation of autoantibodies against platelet-associated antigens, Most antiplatelet autoantibodies react with either the platelet glycoprotein IIb/IIIa or Ib/IX complex, whereas some plasma autoantibodies react: with glycoprotein IIIa. Previous studies from our laboratory suggested that most platelet-associated autoantibodies to platelet GPIIb/IIIa, which bind to the intact complex, bind much less avidly to the EDTA-dissociated complex, suggesting that the epitopes were complex-dependent. To evaluate this further we have studied the binding of platelet-associated autoantibody and plasma auto- and alloantibody eluates to large recombinant GPIIIa peptides: peptide 1 (GPIIIa Gly(1)-Val(200)); peptide 2 (GPIIIa Arg(150)-Glu(400)); peptide 3 (GPIIIa Lys(350)-Asp(550)); peptide 4 (GPIIIa Asn(450)-Val(700)) and peptide 5 (GPIIIa Trp(715)-Thr(762), cytoplasmic fragment). Of the 33 platelet-associated antibody eluates tested, all bound avidly to the GPIIb/IIIa complex, but only one showed significant binding (>3 SD above control values) to one of the immobilized peptides (peptide 3), Conversely, antibodies known to bind to specific regions of GPIIIa (murine monoclonal antibody, anti-LIBS2; plasma autoantibody against the GPIIIa cytoplasmic fragment and anti-Pl(Al) antibody) all bound avidly to the GPIIIa peptide containing the appropriate epitope, Based on these and our previous results, we conclude that platelet-associated antibodies from chronic ITP patients rarely bind to epitopes localized to GPIIIa alone.
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页码:178 / 184
页数:7
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