Characterization of monoclonal anti-β2-glycoprotein-I and anti-prothrombin antibody fragments generated by phage display from a patient with primary antiphospholipid syndrome Academic Article uri icon

Overview

MeSH Major

  • Antibodies, Monoclonal
  • Antiphospholipid Syndrome
  • Glycoproteins
  • Peptide Library
  • Prothrombin

abstract

  • The molecular structure of antibodies associated with autoimmune thrombosis is beginning to be understood. We describe the binding specificities and sequence analysis of anti-beta2-glycoprotein-I (anti-beta2GP-I) or anti-prothrombin (anti-PT) antibody fragments generated by phage display from a patient with primary antiphospholipid syndrome (APS). We obtained 39 positive clones, two that had the correct size reacted with beta2GP-I (Beta 1 and Beta 2). Ten clones with the same restrictive pattern recognized PT (Prot 1) and cross-reacted with beta2GP-I. All three clones recognized anionic and zwitterionic phospholipids. The V(H) regions of both anti-beta2GP-I clones are members of the VH4 family. Prot 1 has a V(H) segment of the VH3 family. The Beta 1 J(H) segments are J(H)5b and J(H)4b for Beta 2 and Prot 1. V(L) genes are V(lambda)1, 3 and 1, respectively. No J(L) was identified for Beta 1, while Beta 2 and Prot 1 carry J(lambda)3b genes. Beta 1 and Beta 2 carry highly conserved germ-line V(H) and V(L) genes. Mutations of the Prot 1 gene appear to be antigen-dependent, most are hotspot mutations located in the CDR 1 and 2 regions. Our work suggests that some anti-beta2GP-I from patients with primary APS are natural autoantibodies. Our work may also help to explain the frequent coexistence of anti-beta2GP-I and anti-PT in the same patient.

publication date

  • February 2006

Research

keywords

  • Academic Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1016/j.jaut.2005.10.002

PubMed ID

  • 16330187

Additional Document Info

start page

  • 57

end page

  • 65

volume

  • 26

number

  • 1