Lupus anticoagulant activity is frequently dependent on the presence of beta 2-glycoprotein I.
Antiphospholipid antibodies (aPL) are defined by anticardiolipin antibody (aCL) ELISA and prolongation of phospholipid dependent coagulation assays (lupus anticoagulant; LAC). For the binding of aCL to cardiolipin a cofactor, beta 2-glycoprotein I (beta 2-GPI), is necessary. We have investigated whether the same cofactor is essential for LAC activity. Plasma from 6 LAC positive patients and 3 controls was depleted from beta 2-GPI by means of affinity chromatography. From the 6 LAC positive plasmas, 4 became LAC negative (tested with dRVVT) when beta 2-GPI was depleted and became positive again when purified beta 2-GPI (200 micrograms/ml) was added. A dose response curve showed that addition of 50 micrograms/ml beta 2-GPI to beta 2-GPI deficient patient plasma, led to a positive dRVVT. Depletion of, and addition of beta 2-GPI to plasma from controls had no effect on the dRVVT. Measurement of beta 2-GPI plasma levels in 19 LAC positive patients, 40 LAC negative patients and 15 controls showed no difference in beta 2-GPI levels. These results show that a combination of aPL and beta 2-GPI is essential not only for binding to cardiolipin, but also for LAC activity and imply that low beta 2-GPI levels (less than 50 micrograms/ml) can lead to false negative LAC tests. These observations may lead to new insights in the pathophysiological complications associated with aPL.
Oosting
J D
JD
Department of Haematology, University Hospital Utrecht, The Netherlands.
Derksen
R H
RH
Entjes
H T
HT
Bouma
B N
BN
de Groot
P G
PG
D000328:Adult; D001053:Apolipoproteins / Q000172:deficiency / Q000502:physiology*; D001323:Autoantibodies / Q000097:blood*; D002846:Chromatography, Affinity; D006023:Glycoproteins / Q000172:deficiency / Q000502:physiology*; D006801:Humans; D007118:Immunoassay / Q000379:methods; D016682:Lupus Coagulation Inhibitor / Q000097:blood*; D008403:Mass Screening / Q000379:methods; D008875:Middle Aged; D010743:Phospholipids / Q000276:immunology*; D011517:Prothrombin Time; D053482:beta 2-Glycoprotein I
D001053:Apolipoproteins; D001323:Autoantibodies; D006023:Glycoproteins; D016682:Lupus Coagulation Inhibitor; D010743:Phospholipids; D053482:beta 2-Glycoprotein I