MOLECULAR-CLONING OF THE COMPLEMENTARY-DNA FOR AN ADDITIONAL MEMBER OF THE FAMILY OF AORTIC-ANEURYSM ANTIGENIC PROTEINS

Purpose: We have purified and partially sequenced a protein from the a dventitia of the human aorta (aortic aneurysm antigenic protein 40 kDa ; AAAP-40) that has homologies to bovine aortic microfibril-associated glycoprotein (MAGP-36). It is immunoreactive with immunoglobulin G (I gGs) purified from the serum and aortic wall of patients with abdomina l aortic aneurysms. AAAP-40 and MAGP-36 have fibrinogen-like and vitro nectin-like moths. Screening an expression library constructed from hu man aortic adventitial messenger RNA has resulted in the cloning of th ree complementary DNAs whose gene products are immunoreactive with imm unoglobulin G from patients with abdominal aortic aneurysms. Two stron gly resemble each other and have been described separately, The purpos e of this article is to report the third clone, Methods: Messenger RNA from a specimen of human aortic aneurysmal adventitia was reverse-tra nscribed for insertion into the phagemid Uni Zap XR (Stratagene). A st rain of Escherichia coli engineered for expression (XL 1-Blue MFR', St ratagene), was transfected, and rabbit antihuman vitronectin antibody was used to identify positive clones. Sequencing of the positive clone s was performed by the Core Laboratories at Columbia University. Resul ts: The hypothetical protein of rAAAP-CL4 (clone 4) shares sequence mo tifs with known microfibril-associated glycoproteins (MAGPs). The reco mbinant protein (rAAAP-CL4) is immunoreactive with serum from patients (three of four abdominal aortic aneurysm sera), In addition, similari ties have been detected with immunoglobulins of the kappa family and w ith a protein from cytomegalovirus that is a potential molecular mimic . Conclusions: There may several members of a novel family of human ao rtic autoantigenic proteins implicated in abdominal aortic aneurysm di sease.