A New Platelet Antigen System, Yuk a /Yuk b

The object of this study was to further localize autoantigenic structures on Ilb-Ila and, if possible, to precisely identify the epitopes recognized by human autoantibodies. In this paper, we identify a 50-kD chymotryptic fragment of i11a that is recognized by a high percentage of human autoantibodies, typified by the prototype IgG autoantibody RA, which binds to I11a on intact platelets as well as in an immunoblot assay under nonreduced conditions. Using an immunoblot assay, a carboxy-terminal region of this fragment (33 kD) that contains the cysteine-rich domains of i11a was found to carry the epitope(s) recognized by the prototype autoantibody RA. The amino-terminal amino acid sequence of the reduced 33-kD fragment, the smallest fragment that retains the RA epitope, is XPSQQDEXSP, and that of the reduced 50-kD fiagment is IVQVTFD. This indicates that the 33-kD fragment consists of -175 amino acids beginning at residue 479 and extending at least through residues 636-654, while the 50-kD fragment spans the same region but begins at residue 427. It is apparent that the 33-kD fragment is generated from the 50-kD fragment by additional chymotryptic hydrolysis but remains associated because of the multiple disulfide bonds that are characteristic of this cysteine-rich domain. Sera from 48% of patients with chronic ITP and 2 of8 patients with acute ITP contain antibodies that bind to the 50-kD fragment in an ELISA. Antibodies of the same specificity are also found in one-third of patients with either secondary immune thrombocytopenia or apparent nonimmune thrombocytopenia. We conclude that the 50-kD cysteine-rich region of lIla is a frequent target of autoantibodies in ITP, but that such antibodies may also be present in cases of thrombocytopenia that cannot be linked to an apparent autoimmune process. (J. Clin. Invest. 1991. 88:847-854.)

Section: Introductionmentioning

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Localization of human platelet autoantigens to the cysteine-rich region of glycoprotein IIIa.

Kekomäki¹,

Dawson²,

McFarland³

et al. 1991

“…Subsequently, one case of PTP associated with an antibody specific for the same antigen, Pena, was reported by Simon et al (2). Also, a recently reported platelet alloantigen system, Yuk, which was the causative factor of several cases of NATP in Japan (13,14) has turned out to be identical to the Pen system (Aster, R. H., and Y. Shibata, unpublished observations In the presence of calcium ions, GPIIIa is complexed with GPIIb constituting a receptor site not only for fibrinogen (27) but also for fibronectin (28) (6) also reported autoantibodies against the GPIIb-IIIa complex in patients with the same disorder.…”

Section: Discussionmentioning

confidence: 98%

“…The antibodies reactive with the Pen3 alloantigen used in this study were from the proband studied by Friedman and Aster (1) and from a second patient with PTP due to anti-Pen' (2). Antisera reactive with the Yuk3 and Yuk" allelic platelet alloantigens (13,14) were a generous gift from Dr. Y. Shibata (Department of Immunohematology, Toranomon Hospital and Okinaka Memorial Institute for Medical Research, Tokyo, Japan). All antisera and plasmas were heat inactivated (56'C for 30 min) before use.…”

Section: Methodsmentioning

confidence: 99%

On the association of the platelet-specific alloantigen, Pena, with glycoprotein IIIa. Evidence for heterogeneity of glycoprotein IIIa.

Furihata

Nugent²,

Bissonette³

et al. 1987

128

“…In 1985, Friedman and Aster (4) reported the first description of the Pen alloantigen system in two cases of NATP, and showed that it was likely to be localized to either GPIIb or GPIIIa. Subsequently, Shibata et al (5) reported an alloantigen system, designated Yuk, responsible for two cases ofNATP in Japan. A case of PTP associated with the Pen alloantigen system was later reported by Simon et al (6).…”

Section: Introductionmentioning

confidence: 99%

An amino acid polymorphism within the RGD binding domain of platelet membrane glycoprotein IIIa is responsible for the formation of the Pena/Penb alloantigen system.

Wang¹,

Furihata²,

McFarland³

et al. 1992

The human Pena/Penb alloantigen system represents a naturally occurring polymorphism of human platelet membrane glycoprotein (GP) MIla, and has previously been implicated in the onset of two important clinical syndromes, neonatal alloimmune thrombocytopenic purpura and posttransfusion purpura. To investigate the molecular basis of the polymorphism underlying the Pen alloantigen system, we used the polymerase chain reaction to amplify platelet-derived GPIIIa mRNA transcripts. DNA sequence analysis of amplified GPIIIa cDNAs from nucleotides 161 to 1341 (encompassing amino acid residues 22-414) revealed a G526 -