TY - JOUR
T1 - ANCA-Associated Vasculitis Pathogenesis
T2 - A Commentary
AU - Gapud, Eric J.
AU - Seo, Philip
AU - Antiochos, Brendan
N1 - Funding Information:
The work reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under Award Number T32AR048522 and by National Institutes of Health Award Number RO1 DE 12354-15A1. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Dr. Gapud is supported by funding from the National Institutes of Health Award Number T32AR048522. Dr. Antiochos is supported by the Jerome L. Greene Foundation and National Institutes of Health Award Number RO1 DE 12354-15A1. Dr. Seo was supported by the Dr. Darwin James Liao Discovery Fund.
Publisher Copyright:
© 2017, Springer Science+Business Media New York.
PY - 2017/4/1
Y1 - 2017/4/1
N2 - Purpose of Review: The ANCA-associated vasculitides are a group of small vessel vasculitides characterized by autoantibodies recognizing the neutrophil cytoplasmic antigens PR3 and MPO. We examine the current clinical and molecular immunology understanding of ANCA-associated vasculitides and discuss the current needs in our understanding of the pathogenic mechanisms of these rare diseases. Recent Findings: The majority of efforts to understand the pathogenesis of these diseases have focused on dissecting neutrophil biology because the neutrophil is the primary expressor of ANCA autoantigens. However, a number of important genetic, clinical, and cellular biology observations suggest that attempts to understand the pathogenesis of ANCA vasculitides should move away from emphasis on the role of the neutrophil and instead re-focus on the potential role of other immune cell mediators. Summary: Whether or not neutrophils are the key determinant of ANCA-associated vasculitis pathogenesis should be revisited in detail. A neutrophil-centric view of the pathogenesis of these diseases cannot fully account for important genetic, clinical, and cellular biology observations that implicate important and under-appreciated roles for monocytes and T cells. Refocusing on these findings will likely lead to new discovery of novel therapeutic targets and the identification of clinically useful biomarkers for disease activity.
AB - Purpose of Review: The ANCA-associated vasculitides are a group of small vessel vasculitides characterized by autoantibodies recognizing the neutrophil cytoplasmic antigens PR3 and MPO. We examine the current clinical and molecular immunology understanding of ANCA-associated vasculitides and discuss the current needs in our understanding of the pathogenic mechanisms of these rare diseases. Recent Findings: The majority of efforts to understand the pathogenesis of these diseases have focused on dissecting neutrophil biology because the neutrophil is the primary expressor of ANCA autoantigens. However, a number of important genetic, clinical, and cellular biology observations suggest that attempts to understand the pathogenesis of ANCA vasculitides should move away from emphasis on the role of the neutrophil and instead re-focus on the potential role of other immune cell mediators. Summary: Whether or not neutrophils are the key determinant of ANCA-associated vasculitis pathogenesis should be revisited in detail. A neutrophil-centric view of the pathogenesis of these diseases cannot fully account for important genetic, clinical, and cellular biology observations that implicate important and under-appreciated roles for monocytes and T cells. Refocusing on these findings will likely lead to new discovery of novel therapeutic targets and the identification of clinically useful biomarkers for disease activity.
KW - AAV pathogenesis
KW - ANCA-associated vasculitis
KW - Eosinophilic granulomatosis with polyangiitis
KW - Granulomatosis with polyangiitis
KW - Microscopic polyangiitis
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U2 - 10.1007/s11926-017-0641-0
DO - 10.1007/s11926-017-0641-0
M3 - Review article
C2 - 28361331
AN - SCOPUS:85016549841
SN - 1523-3774
VL - 19
JO - Current rheumatology reports
JF - Current rheumatology reports
IS - 4
M1 - 15
ER -