Studies on antibodies against phospholipids
Author: Årfors, Leopold
Date: 1997-12-12
Location: Föreläsningssalen på CMM
Time: 9.00
Abstract
The main clinical features of the antiphospholipid syndrome (APLS) are
arterial andvenous thrombosis, repeated spontaneous abortions and
thrombocytopenia. Diagnosedconcomitant with an underlying disease the
designation is secondary APLS; otherwiseprimary APLS. The serological
requirement for the diagnosis is the presence of
antiphospholipidantibodies (APLA). These constitute closely related
antibody specificities, as lupusanticoagulants (LA) and anticardiolipin
antibodies (ACLA).
The aim of this thesis was to study the prevalence of APLA in habitual
abortionand chronic idiopathic thrombocytopenic purpura (ITP) and to
investigate for immunologicaland metabolic derangements of potential
relevance for disease manifestations in APLS.
Of 99 women with habitual abortion, 42 had ACLA and the antibodies were
presentin all IgG subclasses. Ten women with high antibody titers had low
levels of thecomplement component C4 and fragmentation of C2 indicative
of an ongoing complementactivation. Circulating immune complexes (CIC)
were prevalent in the patients, andthus a factor potentially contributing
to complement activation was present.
A significant increase of thromboxane A2 (TXA2) was demonstrated in 31
subjectswith APLS by increased urine concentration of the metabolite
2,3-dinor-TxB2. TXA2is synthesized by activated platelets and has potent
platelet aggregating and vasoconstrictiveproperties. Its actions are
opposed by prostacyclin (PGI2) from endothelial cells(ETC). The PGI2
metabolite 2,3-dinor-6-keto-PGF1a was also increased but not to thesame
extent. The disproportionate increase in TXA2 reflects platelet
activation andmight be of pathogenic relevance in APLS.
Twelve sera out of forty from patients with chronic ITP contained ACLA.
Sera withthese antibodies from 12 non-ITP patients were studied for
reactivity with plateletmembranes. Eight sera showed increased binding of
IgG which was reduced in six afterabsorption with cardiolipin liposomes.
Reactivity against phospholipids should thusbe considered when
interpreting results suggestive of anti-platelet autoantibodies.
CIC from five patients with APLA were isolated and antibody distribution
betweenserum and CIC was determined. The relative concentration and
avidity of the antibodieswas higher in CIC. This could have special
implications with regard to the role ofCIC in platelet and complement
activation and to thrombocytopenia and thrombophiliain APLS.
The in vivo effect of a single oral dose of 500 mg of aspirin on the
biosynthesisof TXA2 was studied in 7 subjects with IgG ACLA by monitoring
the urine excretionof 2,3 dinor-TXB2 for at least seven days. The
decrease in TXA2 formation was between46% and 85%, indicating a less
inhibiting effect of aspirin than in healthy individuals.This might be of
relevance for the dosage of aspirin in conditions in which
plateletactivation is implicated as part of the pathogenic mechanism, as
in the antiphospholipidsyndrome.
Key words: Antiphospholipid syndrome, anticardiolipin antibodies, lupus
anticoagulants,platelets, platelet activation, complement activation,
endothelial cells, thromboxane,prostacyclin, acetylsalicylic acid.
ISBN 91-628-2758-8
Issue date: 1997-11-21
Publication year: 1997
ISBN: 91-628-2758-8
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