A HUMAN MONOCLONAL ANTIPHOSPHOLIPID ANTIBODY THAT IS REPRESENTATIVE OF SERUM ANTIBODIES AND IS GERMLINE ENCODED

Objective. To investigate the origins of antiphospholipid antibodies a ssociated with thrombosis anal other disorders that are found in patie nts with systemic lupus erythematosus and primary antiphospholipid syn drome (APS). Methods. Characterization, idiotypic study, and nucleotid e 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 antib ody, BH1, was generated, This antibody has ligand-binding properties t hat closely resemble those of the serum antiphospholipid antibodies fo und in our patient and in other individuals with APS: it recognizes ne gatively charged phospholipids, and has lupus anticoagulant activity; it does not bind to neutral phospholipids, or to single-stranded or do uble-stranded DNA. The relevance of ]BH1 to the patient's serum antibo dies is supported by our idiotypic studies, BH1 is encoded by a new ge rmline V-H gene, and by a lambda light chain gene that displays > 99% homology with the V lambda III.1 germline gene, Conclusion, Serum anti phospholipid antibodies associated with thrombosis may be encoded by e ither germline or only slightly mutated variable-region genes.