Lupus anticoagulant-like activity observed in a dimeric λ protein produced by myeloma cells

• Published in: International journal of hematology Vol. 73; no. 4; pp. 526 - 531
• Main Authors: SHINAGAWA, Atsushi, KOJIMA, Hiroshi, KOBAYASHI, Toshitaka, KAWADA, Kenichi, NAGASAWA, Toshiro
• Format: Journal Article
• Language: English
• Published: Tokyo Springer 01-06-2001
• Subjects: Bence Jones Protein - isolation & purification; Bence Jones Protein - pharmacology; Bence Jones Protein - urine; Biological and medical sciences; Blood Coagulation - drug effects; Dimerization; Humans; Immunodeficiencies. Immunoglobulinopathies; Immunoglobulin lambda-Chains - isolation & purification; Immunoglobulin lambda-Chains - pharmacology; Immunoglobulin lambda-Chains - urine; Immunoglobulinopathies; Immunopathology; Lupus Coagulation Inhibitor; Male; Medical sciences; Middle Aged; Multiple Myeloma - blood; Partial Thromboplastin Time; Autoimmunity; Human; Immunopathology; Circulating anticoagulant; Autoantibody; Phospholipid; Male; Malignant hemopathy; Myeloma; Bence Jones protein; Case study; Immunoglobulinopathy; Lymphoproliferative syndrome; Complication
• ISSN: 0925-5710; 1865-3774
• DOI: 10.1007/BF02994017

We report here a lupus anticoagulant (LA)-like activity observed in a 45-year-old man with Bence-Jones protein (BJP) lambda-type multiple myeloma. This patient showed no clinical symptoms of thrombosis or bleeding diathesis. Laboratory examination on admission showed mild anemia, prolongation of activated partial thromboplastin time (APTT) (APTT, 56.2 seconds; control, 29.1 seconds), normal prothrombin time, normal thrombin time, and massive proteinuria (2.3 g/d). The mix test with normal plasma showed the presence of circulating anticoagulant. Based on the assumption that the lambda-type BJP may have been responsible for the prolongation of APTT, we purified the BJP from the patient's urine using column works. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting showed that the purified protein was a 48-kd homodimer of immunoglobulin lambda-chains. Addition of the purified dimeric lambda-type BJP to the normal plasma prolonged both APTT and dilute Russell's viper venom time (DRVVT) in a dose-dependent manner, and the negatively charged phospholipid-dependent prothrombinase activity was significantly inhibited in the presence of this protein. Furthermore, both the prolongation of DRVVT and the inhibition of the prothrombinase activity were almost completely abrogated under the condition of high ionic strength. These findings collectively suggest that the dimeric lambda-type BJP showed LA-like activity via the mechanism of ionic charge.