Abstract |
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.
|
Authors | Cees G M Kallenberg |
Journal | Current rheumatology reports
(Curr Rheumatol Rep)
Vol. 12
Issue 6
Pg. 399-405
(Dec 2010)
ISSN: 1534-6307 [Electronic] United States |
PMID | 20878509
(Publication Type: Journal Article, Review)
|
Chemical References |
- Antibodies, Antineutrophil Cytoplasmic
- Peroxidase
- Myeloblastin
|
Topics |
- Animals
- Antibodies, Antineutrophil Cytoplasmic
(blood)
- Cells, Cultured
- Disease Models, Animal
- Humans
- Immunity, Cellular
(immunology)
- Mice
- Microscopic Polyangiitis
(immunology, pathology, physiopathology)
- Myeloblastin
(immunology)
- Neutrophils
(cytology, immunology)
- Peroxidase
(immunology)
- Rats
- Staphylococcus aureus
(immunology, pathogenicity)
- Th17 Cells
(immunology)
|