Demonstration of a circulating antibody in subjects with chronic spinal cord injury

Although coronary artery disease (CAD) is appreciated to be accelerated in patients with chronic spinal cord injury (SCI), the underlying mechanism of CAD in SCI remains obscure. The role of platelet prostacyclin (PGI2) receptors in the development of CAD in SCI was investigated. Incubation of normal, nonSCI platelets in SCI plasma (n=12) resulted in the loss of high affinity binding of PGI₂ to platelets, as determined by using ³H-PGE₁ as a stable probe. The loss of high affinity PGI₂ binding (Kd₁=9 nM) led to the failure of PGI₂ to inhibit the platelet-stimulated thrombin generation. The increase of cellular cyclic AMP level, mediated through the binding of PGI₂ to low affinity receptors in plaletets (Kd₂=0.9 mM), was unaffected in SCI platelets. Polyacrylamide gel electrophoresis (PAGE) and immunoblot of SCI plasma showed the presence of an IgG band, which specifically blocked the binding of ³H-PGE₁ to the high affinity PGI₂ 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 inhibits the binding of ³H-PGE₁ to the high affinity platelet PGI₂ receptor, strongly suggested that the inhibition of high affinity PGI₂ binding to platelets was due to an antibody to the prostacyclin receptor in SCI plasma.