Abstract
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.
Highlights
Antiphospholipid antibodies are defined as immunoglobulins which bind anionic phospholipids
Purification of anti-adenosine triphosphate (ATP) antibodies from the sera of two antiphospholipid syndrome (APS) patients with dementia are presented in Figures 1 and 2
Fractions collected from the column were assayed for IgG content by spectroscopy (280 nm) and by anti-cardiolipin enzyme linked immunosorbent assay (ELISA) as a measure of aPL IgG content
Summary
Antiphospholipid antibodies (aPL) are defined as immunoglobulins which bind anionic phospholipids. A crucial observation has been that aPL, including monoclonal antibodies, cross-react with other relevant protein antigens such as b2-glycoprotein-I (b2GPI, known as apolipoprotein H) (Galli et al 1990, Shoenfeld and Meroni 1992). This protein may serve as a cofactor necessary for the binding of aPL to phospholipids and related antigens such as endothelial cells
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