Page 201 - The Vasculitides, Volume 1: General Considerations and Systemic Vasculitis

In: The Vasculitides, Volume 1 ISBN: 978-1-63463-110-5
Editors: David S. Younger © 2015 Nova Science Publishers, Inc.

Chapter 10

Classification and Pathogenicity
of ANCA-Associated Vasculitis

Constantina Yiannakis, M.D., Lorna Ward, M.D. and
Matthew David Morgan, M.B., Ch.B., M.R.C.P., Ph.D.?

Renal Immunobiology, Centre for Translational Inflammation Research, School of
Immunity and Infection, College of Medical and Dental Sciences,
University of Birmingham, Birmingham, UK

Abstract

Anti-neutrophil cytoplasm antibody-associated vasculitides include several distinct
multisystemic disorders, the diagnosis of which relies upon recognition of a compatible
clinical syndrome supported by radiological, immunological and histological laboratory
findings. If unrecognized, there may be significant delays in treatment culminating in
multiorgan morbidity. Their pathogenesis is complex involving both innate and adaptive
immune systems with loss of tolerance to autoantigens leading to the production of
antibodies that activate cytokine-primed neutrophils. The factors leading to production of
pathogenic autoantibodies is incompletely understood but may involve cross-reactivity to
bacterial antigens and the expression of complementary peptides. T-cells appear to have a
role in both loss of self-tolerance and in the cause of tissue injury. Moreover, peripheral
blood T-cells show evidence of persistent activation driven partly by cytomegalovirus
infection. Activation of the alternative complement pathway has recently emerged as a
significant pathogenic mechanism in the development of glomerulonephritis.

Keywords: ANCA, Vasculitis, Pathogenesis, Classification, ANCA-Associated Vasculitis

? Corresponding author: Matthew David Morgan, M.B., Ch.B., M.R.C.P., Ph.D. Centre for Translational
Inflammation Research, University of Birmingham Research Laboratories, Queen Elizabeth Hospital
Birmingham, Mindelsohn Way, Edgbaston, Birmingham, B15 2WB. E-mail: m.d.morgan @bham.ac.uk.

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