1 research outputs found
Antiphospholipid Antibodies Bind ATP: A putative Mechanism for the Pathogenesis of Neuronal Dysfunction
Antiphospholipid antibodies (aPL) generated in experimental animals
cross-react with ATP. We therefore examined the possibility that aPL IgG from
human subjects bind to ATP by affinity column and an enzyme linked
immunosorbent assay (ELISA). Sera with high levels of aPL IgG were collected
from 12 patients with the antiphospholipid syndrome (APS). IgG fractions from
10 of 12 APS patients contained aPL that could be affinity-bound to an ATP
column and completely eluted with NaCl 0.5 M. A significant (>50%) inhibition
of aPL IgG binding by ATP 5 mM was found in the majority. Similar inhibition
was obtained with ADP but not with AMP or cAMP. All the affinity purified
anti-ATP antibodies also bound β2-glycoprotein-I (β2-GPI, also known as
apolipoprotein H) suggesting that, similar to most pathogenic aPL, their binding
depends on this serum cofactor. We further investigated this possibility and found
that the binding of β2-GPI to the ATP column was similar to that of aPL IgG in
that most was reversed by NaCl 0.5 M. Furthermore, addition of β2-GPI to aPL
IgG significantly increased the amount of aPL binding to an ATP column. We
conclude that aPL IgG bind ATP, probably through β2-GPI. This binding could
interfere
with the normal extracellular function of ATP and similar neurotransmitters