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Blood, 15 June 2001, Vol. 97, No. 12, pp. 3820-3828
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
The clonal analysis of anticardiolipin antibodies in a single
patient with primary antiphospholipid syndrome reveals an extreme
antibody heterogeneity
Patricia Lieby,
Anne Soley,
Honey Levallois,
Benedicte Hugel,
Jean-Marie Freyssinet,
Martine Cerutti,
Jean-Louis Pasquali, and
Thierry Martin
From the Laboratoire d'Immunopathologie and
Laboratoire d'Hématologie, Institut d'Hématologie et
d'Immunologie, Hôpital Civil, Faculté de Médecine de
Strasbourg, Strasbourg, France; Unité 143 INSERM, Hôpital
de Bicêtre, France; and Laboratoire de Pathologie Comparée,
INRA/CNRS URA 2209, Saint-Christol Lez-Alès, France.
The mechanism underlying the prothrombotic state that characterizes
the primary antiphospholipid syndrome proves to be difficult to define
mainly because of the variety of the phospholipid and protein targets
of antiphospholipid antibodies that have been described. Much of the
debate is related to the use of polyclonal antibodies during the
different antiphospholipid assays. To better describe the
antiphospholipid antibodies, a strategy was designed to analyze the
reactivity of each one antibody making up the polyclonal anticardiolipin activity, breaking down this reactivity at the clonal
level. This was performed in a single patient with primary antiphospholipid syndrome by combining (1) the antigen-specific selection of single cells sorted by flow cytometry using structurally bilayered labeled anionic phospholipids and (2) the cloning of immunoglobulin (Ig) variable (V) region genes originating from individual IgG anticardiolipin-specific B cells by a single-cell polymerase chain reaction technique. The corresponding V regions were
cloned in order to express human recombinant antibodies in insect cells
by a baculovirus expression system. The molecular analysis, the fine
specificity, and the protein cofactor dependency of the first 5 monoclonal IgG anticardiolipins are reported here. This clonal analysis
reveals the extreme heterogeneity of these antibodies, which could
account for the difficulties in the previous attempts to define the
pathogenic antiphospholipid response. This approach should help to
unravel the complex antiphospholipid immune response and the
mechanism of the prothrombotic state associated with these
antibodies, but it could also shed some light on their possible origins.
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