TY - JOUR
T1 - ANCA-Associated Vasculitis
T2 - Pathogenesis, Models, and Preclinical Testing
AU - Hutton, Holly L.
AU - Holdsworth, Stephen R.
AU - Kitching, A. Richard
PY - 2017/9/1
Y1 - 2017/9/1
N2 - Summary: Our understanding of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis has developed greatly since the discovery of ANCA, directed against neutrophil components, in 1982. Observations in human disease, and increasingly sophisticated studies in vitro and in rodent models in vivo, have allowed a nuanced understanding of many aspects of the immunopathogenesis of disease, including the significance of ANCA as a diagnostic and monitoring tool as well as a mediator of microvascular injury. The mechanisms of leukocyte recruitment and tissue injury, and the role of T cells increasingly are understood. Unexpected findings, such as the role of complement, also have been uncovered through experimental studies and human observations. This review focusses on the pathogenesis of ANCA-associated vasculitis, highlighting the challenges in finding new, less-toxic treatments and potential therapeutic targets in this disease. The current suite of rodent models is reviewed, and future directions in the study of this complex and fascinating disease are suggested.
AB - Summary: Our understanding of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis has developed greatly since the discovery of ANCA, directed against neutrophil components, in 1982. Observations in human disease, and increasingly sophisticated studies in vitro and in rodent models in vivo, have allowed a nuanced understanding of many aspects of the immunopathogenesis of disease, including the significance of ANCA as a diagnostic and monitoring tool as well as a mediator of microvascular injury. The mechanisms of leukocyte recruitment and tissue injury, and the role of T cells increasingly are understood. Unexpected findings, such as the role of complement, also have been uncovered through experimental studies and human observations. This review focusses on the pathogenesis of ANCA-associated vasculitis, highlighting the challenges in finding new, less-toxic treatments and potential therapeutic targets in this disease. The current suite of rodent models is reviewed, and future directions in the study of this complex and fascinating disease are suggested.
KW - ANCA
KW - glomerulonephritis
KW - immunology
KW - vasculitis
UR - http://www.scopus.com/inward/record.url?scp=85021373767&partnerID=8YFLogxK
U2 - 10.1016/j.semnephrol.2017.05.016
DO - 10.1016/j.semnephrol.2017.05.016
M3 - Review Article
AN - SCOPUS:85021373767
VL - 37
SP - 418
EP - 435
JO - Seminars in Nephrology
JF - Seminars in Nephrology
SN - 0270-9295
IS - 5
ER -