J. Charles Jennette, MD

J. Charles Jennette, MD

Dr. Jennette’s current research focuses on inflammatory vascular disease (vasculitis and glomerulonephritis) caused by anti-neutrophil cytoplasmic autoantibodies (ANCA), which are a major cause for the most common form of aggressive glomerulonephritis and systemic small vessel vasculitis in adults.

In collaboration with Dr. Hong Xiao and Dr. Peiqi Hu, he utilizes animal models of ANCA disease discovered in their laboratory that is induced by mouse anti-myeloperoxidase (anti-MPO) antibodies and is mediated primarily by activation of neutrophils. Activation of the alternative complement pathway is critically involved in the pathogenesis of disease in this model. ANCA-activated neutrophils release factors that activate complement, which in turn primes neutrophils for further activation by ANCA. These effects and other ANCA-mediated pathogenic events depend on generation of C5a by alternative pathway activation and on engagement of C5a receptors on neutrophils. Blockade of this critical pathogenic step abrogates disease induction, which suggests a possible novel therapeutic strategy in humans, which is currently under investigation in patients with ANCA disease. Current studies include investigations of the genes responsible for differences in disease severity, the role of epitope specificity in the pathogenicity of ANCA, the roles of Fc gamma receptors and other innate immune factors in modulating disease phenotype, and studies using a mouse model to elucidate the pathogenesis of ANCA-induced necrotizing pulmonary granulomatosis.