Susac's Syndrome: An Organ Specific Autoimmune Endotheliopathy Syndrome Associated with Antiendothelial Cell Antibodies.
Cynthia M Magro, Jonathan C Poe, Martin Lubow, John O Susac. Weill Cornell Medical College, New York, NY; Duke University Medical Center, Durham, NC; Ohio State University, Columbus; Neurology and Neurosurgery Associates, Winter Haven, FL
Background: Susac's Syndrome (SS) consists of the clinical triad of encephalopathy, branch retinal artery occlusions (BRAO) and hearing loss. While it is well established that SS is due to a microangiopathy, little is known about its pathogenesis with no proven viral or environmental factors.
Design: Twelve patients with SS were encountered by JOS. Serum samples in 11 of these cases were evaluated for antiendothelial cell antibodies (AECA) by an indirect immunofluorescent assay using dermal blood microvascular endothelial cells as substrate as described below. AECA were also assessed via a Western blot technique using cutaneous endothelial cell lysates.
An archival brain biopsy was available on one of these patients. To assess for evidence of classic complement activation unstained slides were provided for C4d and C3d assessment.
Results: Based on distinctive light microscopic findings in brain biopsy material analogous to antiendothelial cell antibody mediated microvascular injury syndromes we postulated that the basis of the SS microangiopathy was one attributable to antiendothelial cell antibodies. In this regard we examined sera on 11 SS patients to assess for antiendothelial cell antibodies (AECA). Nine of the 11 patients were positive by indirect immunofluorescence and via Western blot studies using cutaneous microvascular endothelial cells as substrate.
A highly distinctive band on Western blots corresponding to a 50 kilodalton (kDa) protein was observed in 8 of the 11 positive SS samples, while the serum in the other positive case exhibited specific reactivity with a protein band at 40 kDa. One of the 2 negative cases had inactive SS since 1988; the other case was an abortive variant characterized solely by BRAO.
Conclusions: Susac's syndrome is a distinct autoimmune endotheliopathy syndrome associated with antiendothelial cell antibodies: the antibody target appears to be specific in many cases and may serve as a biomarker of the disease.
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 241, Wednesday Morning