Granulomatosis with polyangiitis pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Ali Poyan Mehr, M.D. [2] Associate Editor(s)-in-Chief: Cafer Zorkun, M.D., Ph.D. [3]Krzysztof Wierzbicki M.D. [4]
Overview
Inflammation with granuloma formation against a nonspecific inflammatory background is the classical tissue abnormality in all organs affected by Wegener's granulomatosis.
Pathogenesis
The pathogenesis of Granulomatosis with polyangiitis is currently unknown. However, several suggestions have been made to identify possible links associated with the disease, such as bacterial infections, failure of B-cells to downregulate, and T cell dysfunction.
Bacterial infections invoke Granulomatosis with polyangiitis by: causing granulocytes to become active and form autoantibodies against microbial antigens and host proteins. This is invoked because of molecular mimicry and superantigens being released from bacteria.[1]
Genetics
Associated Conditions
Gross Pathology
On gross pathology,
Microscopic Pathology
On microscopic histopathology analysis, focal and segmental glomerulitis, presence of non-caseating granuloma, necrotizing vacuities, varied multinucleated giant cells at times are characteristic findings of Wegener's granulomatosis. The following are images of microscopic pathology of Wegener's granulomatosis.
Pathophysiology
It is now widely presumed that the anti-neutrophil cytoplasmic antibodies (ANCAs) are responsible for the inflammation in Wegener's. The typical ANCAs in Wegener's are those that react with proteinase 3, an enzyme prevalent in neutrophil granulocytes.[2] This type of ANCA is also known as cANCA, with the cindicating cytoplasmic (in contrast to pANCA, which is perinuclear).
ANCAs activate neutrophils, increase their adherence to endothelium, and lead to their degranulation. This causes extensive damage to the vessel wall, particularly of arterioles.
The exact cause for the production of ANCAs is unknown, although some drugs have been implicated in secondary forms of Wegener's. As with many autoimmune disorders, the cause is probably genetic predisposition combined with molecular mimicry caused by a virus or bacterium.
References
- ↑ Kain R, Exner M, Brandes R, Ziebermayr R, Cunningham D, Alderson CA; et al. (2008). "Molecular mimicry in pauci-immune focal necrotizing glomerulonephritis". Nat Med. 14 (10): 1088–96. doi:10.1038/nm.1874. PMC 2751601. PMID 18836458.
- ↑ van der Woude FJ, Rasmussen N, Lobatto S, Wiik A, Permin H, van Es LA, van der Giessen M, van der Hem GK, The TH. Autoantibodies against neutrophils and monocytes: tool for diagnosis and marker of disease activity in Wegener's granulomatosis. Lancet1985;1(8426):425-9. PMID 2857806.