A human monoclonal antiphospholipid antibody that is representative of serum antibodies and is germline encoded.
OBJECTIVE
To investigate the origins of antiphospholipid antibodies associated with thrombosis and other disorders that are found in patients with systemic lupus erythematosus and primary antiphospholipid syndrome (APS).


METHODS
Characterization, idiotypic study, and nucleotide sequencing of a human monoclonal antiphospholipid antibody generated from a patient with primary APS. Identification of the germline genes from which the antibody is derived.


RESULTS
A human monoclonal antibody, BH1, was generated. This antibody has ligand-binding properties that closely resemble those of the serum antiphospholipid antibodies found in our patient and in other individuals with APS: it recognizes negatively charged phospholipids, and has lupus anticoagulant activity; it does not bind to neutral phospholipids, or to single-stranded or double-stranded DNA. The relevance of BH1 to the patient's serum antibodies is supported by our idiotypic studies. BH1 is encoded by a new germline VH gene, and by a lambda light chain gene that displays > 99% homology with the V lambda III.1 germline gene.


CONCLUSIONS
Serum antiphospholipid antibodies associated with thrombosis may be encoded by either germline or only slightly mutated variable-region genes.
Harmer
I J
IJ
Royal Postgraduate Medical School, London, England.
Loizou
S
S
Thompson
K M
KM
So
A K
AK
Walport
M J
MJ
Mackworth-Young
C
C
D000595:Amino Acid Sequence; D000818:Animals; D017152:Antibodies, Antiphospholipid / Q000235:genetics / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology*; D000918:Antibody Specificity; D016736:Antiphospholipid Syndrome / Q000235:genetics / Q000276:immunology; D001483:Base Sequence; D004247:DNA / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression / Q000276:immunology; D005803:Genes, Immunoglobulin / Q000235:genetics / Q000276:immunology; D018095:Germ-Line Mutation / Q000276:immunology; D006801:Humans; D007130:Immunoglobulin Idiotypes / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D010743:Phospholipids / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology
D017152:Antibodies, Antiphospholipid; D000911:Antibodies, Monoclonal; D007130:Immunoglobulin Idiotypes; D010743:Phospholipids; D004247:DNA