Antiphosphatidylserine antibodies in human immunodeficiency virus-1
patients with evidence of T-cell apoptosis and mediate antibody- dependent
cellular cytotoxicity [see comments]
F Silvestris, MA Frassanito, P Cafforio, D Potenza, M Di Loreto, M Tucci, MA Grizzuti, B Nico and F Dammacco
Department of Biomedical Sciences and Human Oncology, University of Bari,
Medical School, Bari, Italy.
Serum reactivities to a panel of phospholipid antigens, including
cardiolipin (CL), phosphatidylserine (PS), sphingomyelin,
phosphatidylcholine, and phosphatidylethanolamine, were measured by
enzyme-linked immunosorbent assay in 196 human immunodeficiency virus- l+
(HIV-1+) patients with CDC II to IVC clinical disease. Significant levels
of IgG to CL, PS, or both were observed in 23 patients lacking evidence of
thrombophilic events or any peculiar clinical feature of HIV-1 infection.
Fluorescence-activated cell sorting analyses showed that in vitro apoptosis
of T cells was increased in patients with high serum anti-PS IgG, whereas
the overexpression of Fas/Apo-1 marker was detected in all patients
regardless of their antiphospholipid reactivities. Macrophages from
patients with significant titers of anti- PS IgG antibodies were not
activated by the presence of apoptotic CEM lymphoblasts or by purified
anti-PS IgG from the same patients. By contrast, these antibodies greatly
improved the effector functions of autologous macrophages in
antibody-dependent cellular cytotoxicity (ADCC) assays using 51Cr-labeled
CEM cells, whereas polyspecific IgG were unable to induce an equivalent
cytotoxicity in all instances. An increasing effect on ADCC was also
observed in tests using macrophages from healthy controls to CEM coated
with anti-PS IgG. These results support a potential correlation of anti-PS
specificity with T-cell apoptosis in HIV-1 infection. Because PS is
exteriorized by apoptotic lymphocytes, its persistence may stimulate
antibodies which cooperate with macrophages in the clearance of dead cells
by an enhanced ADCC mechanism. This interpretation could explain the
absence of thrombophilia in HIV-1+ patients with serum elevations of
antiphospholipid reactivities.
Volume 87,
Issue 12,
pp. 5185-5195,
06/15/1996
Copyright © 1996 by The American Society of Hematology
