Work in the past year extended our previous findings on idiopathic thrombocytopenic purpura (ITP) and on drug dependent antibodies that destroy blood cells. We sought identification of epitopes responsible for reactions with glycoprotein Ib/IX, a major target of ITP Abs, by cloning cDNA fragments of the external domain of GPIb/alpha. Proteins expressed in E. coli DH5a cells reacted with ITP Abs. Short peptides within the large reactive protein fragments, chosen for their likelihood of antigenicity, were synthesized. Reactive epitope(s) for six serum Abs was preserved in one peptide spanning amino acids 326 to 346. Studies such as this one offer insight into the pathophysiology of ITP needed to permit design of more specific therapies. Our previous studies indicated that sera from a high percentage of patients with ITP contain autoAbs against external and/or internal epitopes on one or more of several platelet membrane glycoproteins. Reports of others suggest that detection of platelet-associated rather than serum Abs against these GPs is the most sensitive and specific test for ITP. This year we found that eluted platelet-associated Abs did not differ from plasma Abs in the degree of reactivity. For clinical applications, tests utilizing serum are much more practical than those utilizing platelets. Drug Abs: Hemolytic anemias caused by drug-induced Abs are rare but often fatal disorders. Why certain drug Abs target red cells is a question of basic immunologic and physiologic interest. We found this year that 3 hemolytic drug Abs elicited by dissimilar drugs all were dependent on the erythrocyte integral membrane protein, band 3, for reaction. This is the first identification of the specific red cell component involved. Qualitative and quantitative characteristics of band 3 reactions were defined.
| Jin, Lin; Long, Lingyun; Green, Michael A et al. (2009) The alpha-fetoprotein enhancer region activates the albumin and alpha-fetoprotein promoters during liver development. Dev Biol 336:294-300 |
