Granulomatosis with polyangiitis pathophysiology

Revision as of 15:53, 7 November 2016 by Krzys617 (talk | contribs) (→‎Genetics)
Jump to navigation Jump to search

Granulomatosis with polyangiitis Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Granulomatosis with polyangiitis from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Study of Choice

History and Symptoms

Physical Examination

Laboratory Findings

Chest X Ray

CT

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Granulomatosis with polyangiitis pathophysiology On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Granulomatosis with polyangiitis pathophysiology

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Granulomatosis with polyangiitis pathophysiology

CDC on Granulomatosis with polyangiitis pathophysiology

Granulomatosis with polyangiitis pathophysiology in the news

Blogs on Granulomatosis with polyangiitis pathophysiology

Directions to Hospitals Treating Granulomatosis with polyangiitis

Risk calculators and risk factors for Granulomatosis with polyangiitis pathophysiology

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, form autoantibodies against microbial antigens and host proteins.[1].

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.[2]

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. Interleukin 23 causes T cells to become T helper 17 cells that promote Interleukin 17, Interleukin 6, and tumor necrosis factor alpha to produce pro-inflammatory cytokines.

Genetics

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.[3]

Associated Conditions

Microscopic Pathology

On microscopic histopathology analysis, focal and segmental necrotizing glomerulitis, presence of non-caseating granuloma, necrotizing vasculitis, varied multinucleated giant cells at times are characteristic findings of Granulomatosis with polyangiitis. The following is an image of the microscopic pathology of Granulomatosis with polyangiitis: [4]

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.[5] 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

  1. 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.
  2. Culton DA, Nicholas MW, Bunch DO, Zhen QL, Kepler TB, Dooley MA; et al. (2007). "Similar CD19 dysregulation in two autoantibody-associated autoimmune diseases suggests a shared mechanism of B-cell tolerance loss". J Clin Immunol. 27 (1): 53–68. doi:10.1007/s10875-006-9051-1. PMID 17195045.
  3. Xie G, Roshandel D, Sherva R, Monach PA, Lu EY, Kung T; et al. (2013). "Association of granulomatosis with polyangiitis (Wegener's) with HLA-DPB1*04 and SEMA6A gene variants: evidence from genome-wide analysis". Arthritis Rheum. 65 (9): 2457–68. doi:10.1002/art.38036. PMC 4471994. PMID 23740775.
  4. Libre pathology. https://librepathology.org/wiki/Granulomatosis_with_polyangiitis Accessed on November 7, 2016
  5. 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.

Template:WikiDoc Sources