Current Rheumatology Reports

, Volume 12, Issue 6, pp 399-405

First online:

Open Access This content is freely available online to anyone, anywhere at any time.

Pathophysiology of ANCA-Associated Small Vessel Vasculitis

  • Cees G. M. KallenbergAffiliated withDepartment of Rheumatology and Clinical Immunology, University Medical Center Groningen Email author 


Antineutrophil cytoplasmic autoantibodies (ANCAs) directed to proteinase 3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA) are strongly associated with the ANCA-associated vasculitides—Wegener’s granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome. Clinical observations, including the efficacy of B-cell depletion via rituximab treatment, support—but do not prove—a pathogenic role for ANCA in the ANCA-associated vasculitides. In vitro experimental studies show that the interplay of ANCA, neutrophils, the alternative pathway of the complement system, and endothelial cells could result in lysis of the endothelium. A pathogenic role for MPO-ANCA is strongly supported by in vivo experimental studies in mice and rats, which also elucidate the pathogenic mechanisms involved in lesion development. Unfortunately, an animal model for PR3-ANCA–associated Wegener’s granulomatosis is not yet available. Here, cellular immunity appears to play a major role as well, particularly via interleukin-17–producing T cells, in line with granulomatous inflammation in the lesions. Finally, microbial factors, in particular Staphylococcus aureus and gram-negative bacteria, seem to be involved in disease induction and expression, but further studies are needed to define their precise role in disease development.


Wegener’s granulomatosis MPO-ANCA Microscopic polyangiitis hLAMP-2 autoantibodies Churg-Strauss syndrome Staphylococcus aureus Necrotizing crescentic glomerulonephritis FimH ANCA-associated vasculitis Animal models Antineutrophil cytoplasmic autoantibodies Th17 cells ANCA T-regulatory cells Proteinase 3 PR3-ANCA Myeloperoxidase