Linda Kusner, PhD will present new data utilizing MV2C2 antibodies in Myasthenia Gravis. “Survivin is a negative regulator of apoptosis in myasthenia gravis: a human and animal model study” (October 16, 2019)
Survivin is a Negative Regulator of Apoptosis in Myasthenia Gravis: A Human and Animal Model Study
LindaKusner(Washington,DC), XiangyangZhang(Washington,DC), HenryKaminski(Washington, DC)
Introduction: Myasthenia gravis (MG) is caused by autoantibodies directed against the neuromuscularjunction,withthe majorityofpatientsexpressingantibodiestoacetylcholinereceptor (AChR). Autoreactive cells that produce the disease evade the immune checkpoints by an unknown mechanism. Survivin is a member of the inhibitor of apoptosis family and known to be expressed in circulating lymphocytes from MG patients. Survivin expression may be part of a mechanism that inhibits the apoptosis of autoreactive B cells in MG.
Objective: To assess the role of survivin in myasthenia gravis
Methods: The peripheral blood mononuclear cells were obtained from MG patients and non- autoimmune controls and stained with anti-human CD45, T cell marker (CD4), B cell marker (CD20), and anti-Survivin. The extracellular or intracellular survivin expression on human CD20+ or CD4+ lymphocytes were viewed by using BD Celesta analyzer followed by FlowJo software. To target survivin, a monoclonal antibody was developed against survivin peptide (SVN53-67/M57). For the animal model, EAMG was induced and mice stratified into three treatment groups (PBS, anti-Survivin 20 mcg and 100 mcg). EAMG mice were assessed for disease severity, AChR-specific antibody production, and expression of survivin in splenocyte population.
Results: Significantly higher percentage of CD4- CD20+ human B cells showed intracellular survivin expression in MG patients compared to controls. In the animal model of MG, antibody to survivin treatment improved disease severity, reduced AChR-specific antibody titers, and decreased survivin expression in CD3- CD19+ splenic B cells compared to PBS controls.
Summary/Conclusion: Targeting survivin–expressing B cells for elimination may be an effective therapeutic approach