A novel anti-prostacyclin receptor antibody

Coronary artery disease (CAD) is accelerated in patients with chronic spinal cord injury (SCI). Platelets from SCI develop resistance to prostacyclin (PGI2) IKahn et. al. PNAS 93. 245 (1996)]. Loss of the inhibitory effect of PGIj was due to the loss of high-affinity prostanoid receptors. Incubation ot normal platelets, in SCI plasma (n=12) also resulted in the loss ol highaffinity PGI₂ binding (Kd,=9.1+2.0 nM; n,= 170 + 32 sites/cell vs Kd,= 7.2+J.I: iii= 23+_8 sites/cell), with no significant change in the low affinity receptors (Kd,= 1.9+0.1 (iM; n,= 1832+232 sites/cell vs Kd2=1.6+0.1nM; n2=1740+16I sites/cell) as determined by Scatchard analysis of the binding of 'H-PGE,. The loss of highaffinity PCI; binding also inhibited the platelet-stimulated thrombin generation. Increase of cyclic AMP level, due to PGI, binding to low-affinity receptors, was unaffected in SCI platelets. Polyacrylamide gel clectrophoresis (PAGE) and irnmunoblot of SCI plasma showed the presence of an IgG hand, which specifically blocked the binding of'H-PGE, to the high affinity PGI, receptors of normal platelets. PAGE of the reduced IgG band, the amino acid sequence of the novel band as a heavy chain of IgG which specifically recognizes and inhibits the high-affinity PGI₂ binding to platelets was due to an ami prostacyclin receptor antibody present in SCI plasma.