Recurrent macular edema and stroke syndrome in type 1 diabetes mellitus with potent endothelial cell inhibitory autoantibodies.
OBJECTIVE
To describe a case of type 1 diabetes mellitus with recurrent macular edema and stroke in association with potent endothelial cell inhibitory autoantibodies.


METHODS
The clinical, radiologic, and biochemical data from the study patient are presented, as is the bioactivity in endothelial cells from the immunoglobulin G fraction of the patient's serum.


RESULTS
A 52-year-old man with a 15-year history of poorly controlled type 1 diabetes mellitus had diabetic autonomic neuropathy, gastroparesis, depression, macular edema, proliferative retinopathy, diabetic nephropathy, refractory hypertension, and transient ischemic attacks that progressed to recurrent strokes despite aspirin therapy. Magnetic resonance imaging of the brain showed multi-focal, bilateral ischemic infarcts consistent with recurrent stroke affecting small vessels. The patient's serum contained endothelial cell inhibitory autoantibodies; the titer doubled during a 2-year period when the patient required repeated focal laser to treat macular edema and experienced transient ischemic attacks. The IgG autoantibodies induced stress fiber formation and apoptosis in endothelial cells and inhibited neurite outgrowth in rat pheochromocytoma PC12 cells.


CONCLUSIONS
Low concentrations of purified autoantibodies (1-2 μg/mL) induce endothelial cell contraction in vitro, suggesting a role for autoantibodies in modulating endothelial cell permeability, which may affect multiple target organs. Potent IgG autoantibodies may be a useful marker (with a possible pathophysiologic role) in an unusual syndrome characterized by poorly controlled diabetes, hypertension, dementia, and recurrent small-vessel stroke.
Zimering
Mark B
MB
Department of Veterans Affairs, New Jersey Health Care System, Medical Service, Lyons, New Jersey 07939, USA. mark.zimering@med.va.gov
D000818:Animals; D001323:Autoantibodies / Q000009:adverse effects* / Q000097:blood*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000150:complications* / Q000276:immunology; D003928:Diabetic Nephropathies / Q000150:complications / Q000276:immunology; D003930:Diabetic Retinopathy / Q000150:complications / Q000276:immunology; D042783:Endothelial Cells / Q000276:immunology*; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000276:immunology; D008269:Macular Edema / Q000097:blood / Q000150:complications* / Q000175:diagnosis / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016716:PC12 Cells; D051381:Rats; D012008:Recurrence; D020521:Stroke / Q000097:blood / Q000150:complications* / Q000175:diagnosis / Q000276:immunology; D013577:Syndrome
D001323:Autoantibodies