Abstract

Features of IgG Antibodies and Extracellular Vesicles in Patients with Brain Tumors

Xiaoli Yu, Assistant Professor, University of Colorado Anschutz Medical Campus

Glioblastoma (GBM) is the most common malignant primary brain tumor in humans. Meningioma (MMA) is a generally benign brain tumor formed from the meningeal layers of the brain. Previous findings suggest that tumor antibodies have decreased function from subtle proteolytic cleavage. We hypothesized that immunoglobulin G (IgG) antibodies in the plasma of brain tumor patients are abnormal and may play an important role in tumor pathogenesis. Using multiple immunoassays, we characterized IgG antibodies in plasma and in plasma extracellular vesicles (EVs) from patients with GBM, MMA, and controls. Using capture ELISA, we showed that significantly higher levels of Fc heavy chain IgG antibodies and IgG1 subclass are present in GBM plasma compared to MMA. Similarly, EVs purified from GBM plasma contained higher levels of IgG Fc heavy chain compared to that of MMA. In addition, there are no relationship between size and concentration of brain tumor EVs, in contract to a strong correlation found in EVs from healthy plasma. Proteomics analysis revealed the unique protein profiles between brain tumor EVs and control EVs. We further demonstrated that both GBM plasma and cell line EVs produce complement-dependent cytotoxicity in human neurons and mouse brain tissues in dose- and time-dependent manner. The higher levels of IgG in the plasma and EVs in GBM patients, and the high capacity of cell killing suggest that GBM IgG antibodies and EVs may play an important role in tumor pathogenesis.