A human monoclonal antiphospholipid antibody that is representative of serum antibodies and is germline encoded

Arthritis Rheum. 1995 Aug;38(8):1068-76. doi: 10.1002/art.1780380808.

Abstract

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.

Conclusion: Serum antiphospholipid antibodies associated with thrombosis may be encoded by either germline or only slightly mutated variable-region genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Antiphospholipid / genetics
  • Antibodies, Antiphospholipid / immunology*
  • Antibodies, Monoclonal / genetics
  • Antibodies, Monoclonal / immunology*
  • Antibody Specificity
  • Antiphospholipid Syndrome / genetics
  • Antiphospholipid Syndrome / immunology
  • Base Sequence
  • DNA / immunology
  • Enzyme-Linked Immunosorbent Assay
  • Gene Expression / immunology
  • Genes, Immunoglobulin / genetics
  • Genes, Immunoglobulin / immunology
  • Germ-Line Mutation / immunology
  • Humans
  • Immunoglobulin Idiotypes / immunology
  • Mice
  • Molecular Sequence Data
  • Phospholipids / immunology
  • Phospholipids / metabolism
  • Protein Binding / physiology

Substances

  • Antibodies, Antiphospholipid
  • Antibodies, Monoclonal
  • Immunoglobulin Idiotypes
  • Phospholipids
  • DNA

Associated data

  • GENBANK/L26399
  • GENBANK/L26400
  • GENBANK/L26401
  • GENBANK/L26402
  • GENBANK/L26403