Heterogeneity of anti-phospholipid and anti-endothelial cell antibodies.
The role of the anti-phospholipid antibodies (APLA) and anti-endothelial cell antibodies (AECA) in the pathogenesis of anti-phospholipid syndrome (APS) is unclear. Differences in the reported involvement of APLA may be due, in part, to the polyclonal nature of these antibodies and the use of serum and serum fractions for analysis. To circumvent this issue, we generated monoclonal antibodies (MAB) from three patients with APS and two healthy controls. We then compared the antigen binding patterns and the heavy chain variable region (VH) DNA sequences of the MAB derived from patients with APS to those from healthy controls. The results of this study indicate that APLA and AECA comprise a highly heterogeneous population of antibodies with respect to the antigens they recognize, as well as VH gene usage. MAB derived from patients with APS do not differ from those derived from normal individuals based on either antigen recognition or VH gene usage. These results suggest the importance of additional predisposing factors in the pathogenesis of APS.
Shan
H
H
Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, 3400 Spruce Street, Philadelphia, PA, 19104, USA.
Goldman
J
J
Cunto
G
G
Manuppello
J
J
Chaiken
I
I
Cines
D B
DB
Silberstein
L E
LE
D000595:Amino Acid Sequence; D017153:Antibodies, Anticardiolipin / Q000097:blood / Q000235:genetics / Q000276:immunology; D017152:Antibodies, Antiphospholipid / Q000097:blood / Q000235:genetics* / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000097:blood / Q000235:genetics* / Q000276:immunology; D016736:Antiphospholipid Syndrome / Q000097:blood / Q000235:genetics / Q000276:immunology; D001483:Base Sequence; D004247:DNA / Q000032:analysis / Q000235:genetics; D004730:Endothelium, Vascular / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D006023:Glycoproteins / Q000097:blood; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D008969:Molecular Sequence Data; D010743:Phospholipids / Q000378:metabolism; D016133:Polymerase Chain Reaction; D053482:beta 2-Glycoprotein I
D017153:Antibodies, Anticardiolipin; D017152:Antibodies, Antiphospholipid; D000911:Antibodies, Monoclonal; D000939:Epitopes; D006023:Glycoproteins; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D010743:Phospholipids; D053482:beta 2-Glycoprotein I; D004247:DNA