Molecular cloning of the complementary DNA for an additional member of the family of aortic aneurysm antigenic proteins,☆☆,

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Abstract

Purpose: We have purified and partially sequenced a protein from the adventitia 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 (IgGs) purified from the serum and aortic wall of patients with abdominal aortic aneurysms. AAAP-40 and MAGP-36 have fibrinogen-like and vitronectin-like motifs. Screening an expression library constructed from human aortic adventitial messenger RNA has resulted in the cloning of three complementary DNAs whose gene products are immunoreactive with immunoglobulin G from patients with abdominal aortic aneurysms. Two strongly resemble each other and have been described separately. The purpose of this article is to report the third clone.

Methods: Messenger RNA from a specimen of human aortic aneurysmal adventitia was reverse-transcribed for insertion into the phagemid Uni Zap XR (Stratagene). A strain of Escherichia coli, engineered for expression (XL 1-Blue MFR`, Stratagene), was transfected, and rabbit antihuman vitronectin antibody was used to identify positive clones. Sequencing of the positive clones was performed by the Core Laboratories at Columbia University.

Results: The hypothetical protein of rAAAP-CL4 (clone 4) shares sequence motifs with known microfibril-associated glycoproteins (MAGPs). The recombinant protein (rAAAP-CL4) is immunoreactive with serum from patients (three of four abdominal aortic aneurysm sera). In addition, similarities have been detected with immunoglobulins of the κ family and with a protein from cytomegalovirus that is a potential molecular mimic.

Conclusions: There may several members of a novel family of human aortic autoantigenic proteins implicated in abdominal aortic aneurysm disease. (J Vasc Surg 1997 26:313-8.)

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Supported by the Special Fund for Resident Research, Department of Surgery, St. Luke's/Roosevelt Hospital Center, New York, N.Y.

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Reprint requests: M. David Tilson, MD, St. Luke's/Roosevelt Hospital Center, 1000 Tenth Ave., New York, NY 10019.

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