Granulomatosis with polyangiitis pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. Ali Poyan Mehr, M.D.  Associate Editor(s)-in-Chief: Amandeep Singh M.D.Krzysztof Wierzbicki M.D. Cafer Zorkun, M.D., Ph.D. Amandeep Singh M.D.
The pathogenesis of granulomatosis with polyangiitis is currently unknown. However, several hypothesizes have been made to identify possible links associated with this disease, such as bacterial infections, failure of B-cells to downregulate, and T cell dysfunction. The genetic component of granulomatosis with polyangiitis is not fully known. However, there seems to be a strong correlation between HLA-DPB1 and HLA-DPB2 with granulomatosis with polyangiitis.
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.
Role of bacterial antigens
- Bacterial infections invoke granulomatosis with polyangiitis by: causing granulocytes to become active, forming autoantibodies against microbial antigens and host proteins.
Role of auto-immunity
- Another possible cause of this disease is the failure of B cells to downregulate ANCA autoimmunity because of CD19 dysregulation at two stages.
- The first is CD19 naïve B cells, the dysregulation of CD19 B naïve cells may result in B cells to be autoreactive and have the ability to activate themselves.
- Another stage of dysregulation is CD19 memory B cells, this allows increased sensitive to reactivate B cells.
Dysfunction of T regulator cells
- The last pathogenic cause of ANCA is the dysfunction of T regulator cells (CD4+ CD25+). An imbalance between effector cells and regulatory T cells invokes the development of ANCA.
- The presence of ANCA, induces Interleukin 23 (Il-23) to produce T helper 17 cells. The production of T helper 17 cells promotes the production of Il-17, IL-6, and tumor necrosis factor alpha (TNF-α) which invokes the inflammation of cytokines. 
- The inflammation due to cytokines and the presence of ANCA allows neutrophils to bind TNFα that are actively present on the endothelium, ANCA can cause neutrophils to become active.
- This is due to fragment secondary antibodies of ANCA that bind to proteinase 3 or myeloperoxidase.
- The Fragment crystallizable (Fc) binds to the Fragment crystallizable- gamma receptor (Fc-γ) which allows neutrophils to become active. With this activation, the endothelium becomes destroyed. This is due to degranulation and reactive oxygen species. 
- The genetic component of granulomatosis with polyangiitis is not fully known.
- However, there seems to be a strong correlation between HLA-DPB1 and HLA-DPB2 with granulomatosis with polyangiitis.
- The genetic inheritance of Granulomatosis with polyangiitis is not common.
The following conditions are associated with Granulomatosis with polyangiitis:
- On gross pathology, following are non specific findings in Granulomatosis with polyangiitis:
Granulomatosis with polyangiitis-Case courtesy of Dr. Yale Rosen
Granulomatosis with polyangiitis- By Yale Rosen from USA 
- On microscopic histopathology analysis,the characteristic findings of GPA are:are characteristic findings of Granulomatosis with polyangiitis.
- Focal and segmental necrotizing glomerulitis
- Presence of non-caseating granuloma
- Necrotizing vasculitis
- Varied multinucleated giant cells at times
Granulomatosis with polyangiitis
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- Case courtesy of Dr. Yale Rosen. https://radiopaedia.org/cases/8950 Accessed on March 29, 2018
- (Wegener's granulomatosis Uploaded by CFCF) [CC BY-SA 2.0 (https://creativecommons.org/licenses/by-sa/2.0)]
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- Muller K, Lin JH (2014). "Orbital granulomatosis with polyangiitis (Wegener granulomatosis): clinical and pathologic findings". Arch Pathol Lab Med. 138 (8): 1110–4. doi:10.5858/arpa.2013-0006-RS. PMC 4140401. PMID 25076302.
- Libre pathology. https://librepathology.org/wiki/Granulomatosis_with_polyangiitis Accessed on March 29, 2018