Cardiovascular Antibodies and Orthostatic Hypotension

Accumulating clinical and experimental evidence has identified an increasing array of humoral autoantibodies that disrupt cardiovascular autonomic function. Their diverse clinical presentations encompass bradyarrhythmias, tachyarrhythmias, and hypotension. For example, fetal exposure to maternal anti-Ro or anti-La antibodies in systemic lupus erythematosis may produce complete heart block. In Chagas disease, anti-M2 receptor antibodies are associated with dilated cardiomyopathy, QT dispersion, and atrial fibrillation. Anti-β₁ and anti-β₂ adrenergic receptor antibodies are associated with inappropriate sinus tachycardia and atrioventricular block. Anti-sinus node antibodies are associated with sick sinus syndrome. Anti-N-methyl-D-aspartate (NMDA) receptor antibodies, which cause autoimmune encephalitis, can also cause tachycardia or bradycardia with sinus arrest and asystole. Anti-myosin heavy chain antibodies can cause atrial fibrillation. Antibodies to voltage-gated potassium channel subfamily H (KCNH₂) and, as we have described, to the ganglionic α3-acetylcholine (G-ACh) receptor have been associated with QT dispersion and ventricular tachycardia. Functional autoantibodies associated with neurogenic orthostatic hypotension include those to G-ACh receptors, β₂ adrenergic receptors, and M2 muscarinic receptors. Recognition of these syndromes is revealing an autoimmune basis in a subset of a number of common cardiovascular autonomic conditions that were previously idiopathic and highlights the multiple levels of interaction between the immune system and autonomic neurons. Ongoing research in this area holds promise for elucidating the cellular and synaptic pathophysiological mechanisms underlying autoimmune cardiovascular autonomic disorders, which is an essential step toward discovering more effective treatments and prevention strategies.