Characteristics of human immunodeficiency virus and chlorpromazine induced antiphospholipid antibodies: effect of beta 2 glycoprotein I on binding to phospholipid.
OBJECTIVE
To investigate the nature of the target epitope for human immunodeficiency virus (HIV) and chlorpromazine (CPZ) induced antiphospholipid antibodies (aPL) by evaluating the effect of the aPL cofactor (beta 2 glycoprotein I) on phospholipid binding and to compare this with known binding patterns of infection induced and autoimmune aPL.


METHODS
aPL positive sera from 17 patients with HIV and 16 patients with schizophrenia treated with CPZ were tested and compared with aPL positive sera from 20 patients with syphilis and 35 with autoimmune disease. Both the sera and either IgG fractions prepared by affinity chromatography or IgM fractions prepared by euglobulin precipitation and gel filtration were tested for binding to cardiolipin (CL) in ELISA in the presence and absence of purified human beta 2 glycoprotein I (beta 2-GPI). Competition studies evaluated biotinylated CPZ IgM aPL binding and the effect on this of added aPL, placental anticoagulant protein I--a phospholipid binding protein that inhibits autoimmune aPL--and CL vesicles.


RESULTS
HIV IgG aPL binding to CL was inhibited by beta 2-GPI (51-53%), like syphilis IgG aPL and in contrast to autoimmune IgG aPL. CPZ IgM aPL, like autoimmune IgM aPL, bound more efficiently in the presence of beta 2-GPI, with binding increases of 31-149%. Binding of biotinylated CPZ IgM aPL to CL was competitively inhibited by autoimmune IgG aPL (47%) and CPZ aPL (92%) but not by HIV IgG aPL or normal IgG. Placental anticoagulant protein I and CL vesicles completely prevented binding of CPZ IgM aPL to CL (100 and 96% inhibition, respectively).


CONCLUSIONS
Findings indicate that CPZ aPL resembles the autoimmune aPL, whereas aPL found in HIV infection do not appear to be of autoimmune type.
Gharavi
A E
AE
Antiphospholipid Research Laboratory, New Orleans 70112.
Sammaritano
L R
LR
Wen
J
J
Miyawaki
N
N
Morse
J H
JH
Zarrabi
M H
MH
Lockshin
M D
MD
D017152:Antibodies, Antiphospholipid / Q000032:analysis*; D001053:Apolipoproteins / Q000494:pharmacology; D015551:Autoimmunity / Q000276:immunology; D002746:Chlorpromazine / Q000494:pharmacology*; D006023:Glycoproteins / Q000494:pharmacology*; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D010743:Phospholipids / Q000276:immunology*; D053482:beta 2-Glycoprotein I
D017152:Antibodies, Antiphospholipid; D001053:Apolipoproteins; D006023:Glycoproteins; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D010743:Phospholipids; D053482:beta 2-Glycoprotein I; D002746:Chlorpromazine