Publication

The role of myeloperoxidase in the pathogenesis of systemic vasculitis

Rutgers, A., Heeringa, P. & Tervaert, J. W., 27-Jan-2004, In : Clinical and Experimental Rheumatology. 21, 6 Suppl 32, p. S55-S63 9 p.

Research output: Contribution to journalReview articleAcademicpeer-review

Wegener's granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome and idiopathic pauci-immune necrotizing crescentic glomerulonephritis are strongly associated with the presence of anti-neutrophil cytoplasmic antibodies (ANCA). These ANCA-associated vasculitides can serologically be separated into myeloperoxidase (MPO)-ANCA and proteinase 3 (PR3)-ANCA positive patients. The unique properties of the antigen targeted by the anti-MPO antibodies could help to explain the specific characteristics of MPO-ANCA associated disease. Recently, an animal model has been developed that proves that anti-mouse MPO immunoglobulins alone are capable of causing disease similar to that in humans. Also, the in vitro pathologic effects of binding of, MPO-ANCA to MPO are better understood.

MPO-ANCA can activate (primed) neutrophils directly causing extensive reactive oxygen species formation and degranulation of neutrophil constituents, including MPO, resulting in a destructive inflammatory response towards the vessel wall. MPO-ANCA can prevent the clearing and inactivation of MPO by ceruloplasmin as well, resulting in increased myeloperoxidase activity. Myeloperoxidase produces not only the strong oxidant bleach (hypochlorous acid) out of hydrogen peroxide and chloride ions but also oxidizes LDL into a macrophage high-uptake form, inactivates protease inhibitors, and consumes nitric oxide. These may contribute to endothelial dysfunction and add to the chronic renal lesions observed in patients with MPO-ANCA. MPO levels are influenced by genetic factors including two, MPO463 and MPO129, single nucleotide polymorphisms. The MPO 463 polymorphism has been associated with an increased risk of development of MPO-ANCA associated disease.

Original languageEnglish
Pages (from-to)S55-S63
Number of pages9
JournalClinical and Experimental Rheumatology
Volume21
Issue number6 Suppl 32
Publication statusPublished - 27-Jan-2004

    Keywords

  • peroxidase, antineutrophil, cytoplasmic antibodies, vasculitis, single nucleotide polymorphism, animal models, hypochlorous acid, nitric oxide, CHURG-STRAUSS-SYNDROME, ANTINEUTROPHIL-CYTOPLASMIC ANTIBODIES, AUTOANTIBODY-ASSOCIATED GLOMERULONEPHRITIS, HYPOCHLORITE-MODIFIED PROTEINS, ANCA-ASSOCIATED VASCULITIS, NITRIC-OXIDE SYNTHASE, TERM FOLLOW-UP, ANTIMYELOPEROXIDASE ANTIBODIES, CRESCENTIC GLOMERULONEPHRITIS, MICROSCOPIC POLYANGIITIS

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