Antibody titers predict clinical features of autoimmune autonomic ganglionopathy.
Autoimmune autonomic ganglionopathy is a disorder of isolated autonomic failure associated with antibodies to the nicotinic acetylcholine receptor of the autonomic ganglia resulting in severe orthostatic intolerance, syncope, constipation, gastroparesis, urinary retention, dry mouth, dry eyes, blurred vision and anhidrosis. We report the autonomic test results, antibody titers and clinical findings in 8 patients with antibodies to the nicotinic acetylcholine receptor of the autonomic ganglia. There was a sigmoidal relation between the antibody titers and the fall in systolic blood pressure (r(2)=0.84). The threshold occurred with antibody titers of approximately 1 nmol/l. Over the linear portion of the sigmoid curve, with antibody titers in the 1-3 nmol/l range, increasing antibody titers resulted in more severe orthostatic hypotension (r=0.94, P<0.001). The saturation point of the sigmoidal relation occurred at approximately 3 nmol/l with drops in systolic blood pressure of approximately 100 mmHg during upright tilt. The antibody titers correlated inversely with the Valsalva ratio (r=-0.87, P<0.001), the 30:15 ratio (r=-0.84, P<0.001) and the expiratory to inspiratory ratio (r=-0.67, P<0.01). Patients with orthostatic intolerance, anhidrosis, constipation, urinary dysfunction, sicca syndrome and pupillary dysfunction had higher antibody titers than subjects that did not (P<0.01 in all cases). Autoimmune autonomic ganglionopathy is a clinically heterogeneous disease with variable presentation, particularly in subjects with lower antibody titers. Our data suggest that patients with higher antibody titers have wide spread dysautonomia while those with lower antibody levels may present with, or evolve into, more focal or restricted presentations.
Gibbons
Christopher H
CH
Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Freeman
Roy
R
D000328:Adult; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D001324:Autoantigens / Q000276:immunology*; D020274:Autoimmune Diseases of the Nervous System / Q000188:drug therapy / Q000276:immunology* / Q000503:physiopathology; D003248:Constipation / Q000209:etiology; D018450:Disease Progression; D005260:Female; D005725:Ganglia, Autonomic / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D007007:Hypohidrosis / Q000209:etiology; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D010641:Phenotype; D054972:Postural Orthostatic Tachycardia Syndrome / Q000209:etiology; D011241:Prednisone / Q000627:therapeutic use; D054969:Primary Dysautonomias / Q000188:drug therapy / Q000276:immunology* / Q000503:physiopathology; D011681:Pupil Disorders / Q000209:etiology; D011978:Receptors, Nicotinic / Q000276:immunology*; D012791:Shy-Drager Syndrome / Q000209:etiology; D012859:Sjogren's Syndrome / Q000209:etiology; D014555:Urination Disorders / Q000209:etiology
D001323:Autoantibodies; D001324:Autoantigens; D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D011241:Prednisone; D011978:Receptors, Nicotinic