Blood, Vol. 95 No. 6 (March 15), 2000:
pp. 1988-1992
Rifampicin-dependent antibodies bind a similar or identical
epitope to glycoprotein IX-specific quinine-dependent
antibodies
Janette K. Burgess,
Jose A. Lopez,
Leonie E. Gaudry, and
Beng H. Chong
From the Centre for Thrombosis and Vascular Research, University of
New South Wales, and Department of Hematology, Prince of Wales
Hospital, Sydney, Australia; and Baylor College of Medicine, Houston,
TX.
The drug-dependent antibody of a patient with rifampicin-induced
thrombocytopenia was characterized using the antigen-capture enzyme-linked immunosorbent assay (MAIPA assay), flow cytometry, and
immunoprecipitation. The antibody was found to bind glycoprotein (GP)
Ib-IX but not GPIIb-IIIa because (1) it immunoprecipitated drug-dependently the former but not the latter glycoprotein complex and (2) the MAIPA assay showed strong rifampicin-dependent
antibody binding when anti-GPIb-IX monoclonal antibodies (mAbs) (AK2
and FMC25) but not anti-GPIIb-IIIa mAbs (AP2, SZ21, and SZ22) were used
to capture the antigen. The antibody binding site was further localized
to the GPIX subunit of the GPIb-IX complex because flow cytometric
analysis revealed drug-dependent antibody binding to L cells
transfected with human GPIb
and GPIX complementary DNA (L IX
cells) but not with human GPIb
and GPIb complementary DNA (L
cells). Finally, in the MAIPA assay, the rifampicin-dependent antibody almost completely cross-blocked the binding of the anti-GPIX mAb (SZ1) to platelets. Similar cross-blocking of SZ1binding to platelets by the quinine-dependent antibodies was also observed. This
finding not only confirms that the epitope of the rifampicin-dependent antibody is on GPIX but it is also identical to or located in close
proximity to that of the quinine-dependent antibody and SZ1. Further
characterization of the epitopes of these antibodies may have important
implications for a general understanding of the mechanism of
drug-induced thrombocytopenia.
