Pathogenesis of antineutrophil cytoplasmic autoantibody... : Current Opinion in Nephrology and Hypertension (original) (raw)
Renal immunology and pathology: Edited by Agnes B. Fogo
aDepartment of Pathology and Laboratory Medicine, USA
bDivision of Nephrology and Hypertension, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
Correspondence to J. Charles Jennette, MD, Brinkhous Distinguished Professor and Chair, Department of Pathology and Laboratory Medicine, 308 Brinkhous-Bullitt Building, University of North Carolina, Chapel Hill, NC 27599-7525, USA Tel: +1 919 966 4676; fax: +1 919 966 4542; e-mail: [email protected]
Current Opinion in Nephrology and Hypertension 20(3):p 263-270, May 2011. | DOI: 10.1097/MNH.0b013e3283456731
Abstract
Purpose of review
Antineutrophil cytoplasmic autoantibodies (ANCAs) are associated with vasculitis. Current therapy involves administration of toxic therapy that is not optimally effective. This review will summarize evidence for the pathogenicity of ANCAs, which will suggest possible strategies for improving treatment.
Recent findings
Pauci-immune small vessel vasculitis is associated with antibodies against myeloperoxidase (MPO-ANCA) and proteinase 3 (PR3-ANCA). One research group has reported a high frequency of autoantibodies against lysosomal-associated membrane protein 2 (LAMP-2) in patients with MPO-ANCA or PR3-ANCA. Epigenetic dysregulation appears to be the basis for increased MPO and PR3 neutrophil gene expression in ANCA disease. Release of neutrophil extracellular traps may be involved in initiating the ANCA autoimmune response and causing vessel injury. Generation of C5a by alternative pathway activation is involved in pathogenesis in mouse models. Intervention strategies in mice that target antigens, antibodies and inflammatory signaling pathways may translate into novel therapies. Animal models of LAMP-ANCA and PR3-ANCA disease have been proposed. Molecular mimicry and responses to complementary peptides may be initiating events for ANCAs. T cells, including regulatory T cells, have been implicated in the origin and modulation of the ANCAs, as well as in the induction of tissue injury.
Summary
Our basic understanding of the origins and pathogenesis of ANCA disease is advancing. This deeper understanding already has spawned novel therapies that are being investigated in clinical trials. This brief review shows that there are more questions than answers, and new questions are emerging faster than existing questions are being answered.
© 2011 Lippincott Williams & Wilkins, Inc.