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  • Immune Response Profiling of Serum Identifies Autoantibodies Specific to Moyamoya Patients

    Final Number:
    1433

    Authors:
    Tara Sigdel; Lori Shoemaker PhD; Rong Chen; Minnie Sarwal; Gary K. Steinberg MD PhD

    Study Design:
    Laboratory Investigation

    Subject Category:

    Meeting: Congress of Neurological Surgeons 2012 Annual Meeting

    Introduction: Moyamoya Disease (MMD) is characterized by the progressive occlusion of the internal carotid arteries (ICA), as well as the proximal anterior and middle cerebral arteries (ACA and MCA respectively), together with the development of fragile, collateral vessels. Early diagnosis is often made angiographically, following clinical presentation of hemorrhage or other severe neurological deficits. The etiology of MMD is currently unknown, although several MMD-associated loci and individual gene mutations have been identified. Existing research suggests that MMD may have an autoimmune-related component, given that MMD is also associated with several other disorders, including neurofibromatosis and Graves’s disease. In addition, other groups have reported elevated levels of several autoantibodies, such as anti-cardiolipin, anti-thyroid and anti–a-fodrin.

    Methods: To examine the potential role of autoimmunity in MMD, we profiled autoantibody expression in serum obtained from Moyamoya patients, using commercially available high density autoantibody arrays. The results were validated with ELISA antibody assays.

    Results: Using high density autoantibody arrays, we identified over 186 circulating autoantibodies in sera collected from MMD patients. We have identified high expression of 6 autoantibodies specifically associated with active MMD compared to post-surgery levels. Using antibody ELISA assays, we have further validated levels of autoantibodies against APP, GPS1, STRA13 and CTNNB1. A significant association with T cell receptor signaling, axon guidance, and ErbB signaling was observed.

    Conclusions: Autoantibodies may be produced as a result of exposure to protein antigens during tissue injury or remodeling, expression of elevated or mutated forms of a protein, or molecular mimicry. These findings may provide a basis for novel diagnostic and therapeutic approaches and will advance our understanding of MMD basic disease biology.

    Patient Care: Future work will involve determining the biological significance of the expression of these autoantibodies. These findings may provide a basis for novel diagnostic and therapeutic approaches and will advance our understanding of MMD basic disease biology.

    Learning Objectives: By the conclusion of this session, participants should be able to: 1) Describe and discuss the potential role of the autoimmune system in the context of Moyamoya Disease

    References:

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