Granulomatosis with polyangiitis pathophysiology: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
 
(7 intermediate revisions by 2 users not shown)
Line 1: Line 1:
__NOTOC__
__NOTOC__
{{Wegener's granulomatosis}}
{{Wegener's granulomatosis}}
{{CMG}}{{APM}} {{AE}}{{KW}}{{CZ}}{{ADS}}
{{CMG}}{{APM}} {{AE}}{{ADS}}{{KW}}{{CZ}}{{ADS}}


==Overview==
==Overview==
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.<ref name="pmid23740775" />
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 [[Infection|bacterial infections]], failure of [[B cell|B-cells]] to downregulate, and [[T cell|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.


==Pathogenesis==
==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.
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 [[Infection|bacterial infections]], failure of [[B cell|B-cells]] to downregulate, and [[T cell]] dysfunction.


=== Role of bacterial antigens ===
=== Role of bacterial antigens ===
* Bacterial infections invoke Granulomatosis with polyangiitis by: causing granulocytes to become active, forming autoantibodies against microbial antigens and host proteins.<ref name="pmid18836458">{{cite journal| author=Kain R, Exner M, Brandes R, Ziebermayr R, Cunningham D, Alderson CA et al.| title=Molecular mimicry in pauci-immune focal necrotizing glomerulonephritis. | journal=Nat Med | year= 2008 | volume= 14 | issue= 10 | pages= 1088-96 | pmid=18836458 | doi=10.1038/nm.1874 | pmc=2751601 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18836458  }} </ref>.
* [[Infection|Bacterial infections]] invoke [[granulomatosis with polyangiitis]] by: causing [[Granulocyte|granulocytes]] to become active, forming [[Autoantibody|autoantibodies]] against microbial antigens and host proteins.<ref name="pmid18836458">{{cite journal| author=Kain R, Exner M, Brandes R, Ziebermayr R, Cunningham D, Alderson CA et al.| title=Molecular mimicry in pauci-immune focal necrotizing glomerulonephritis. | journal=Nat Med | year= 2008 | volume= 14 | issue= 10 | pages= 1088-96 | pmid=18836458 | doi=10.1038/nm.1874 | pmc=2751601 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18836458  }} </ref>  


=== Role of auto-immunity ===
=== 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.  
* Another possible cause of this disease is the failure of [[B cell|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.  
* 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.<ref name="pmid17195045">{{cite journal| author=Culton DA, Nicholas MW, Bunch DO, Zhen QL, Kepler TB, Dooley MA et al.| title=Similar CD19 dysregulation in two autoantibody-associated autoimmune diseases suggests a shared mechanism of B-cell tolerance loss. | journal=J Clin Immunol | year= 2007 | volume= 27 | issue= 1 | pages= 53-68 | pmid=17195045 | doi=10.1007/s10875-006-9051-1 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17195045  }} </ref>
* Another stage of dysregulation is CD19 memory B cells, this allows increased sensitive to reactivate [[B cell|B cells]].<ref name="pmid17195045">{{cite journal| author=Culton DA, Nicholas MW, Bunch DO, Zhen QL, Kepler TB, Dooley MA et al.| title=Similar CD19 dysregulation in two autoantibody-associated autoimmune diseases suggests a shared mechanism of B-cell tolerance loss. | journal=J Clin Immunol | year= 2007 | volume= 27 | issue= 1 | pages= 53-68 | pmid=17195045 | doi=10.1007/s10875-006-9051-1 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17195045  }} </ref>


=== Dysfunction of T regulator 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 last pathogenic cause of [[Anti-neutrophil cytoplasmic antibody|ANCA]] is the dysfunction of T regulator cells (CD4+ CD25+). An imbalance between effector cells and [[Regulatory T cell|regulatory T cells]] invokes the development of [[Anti-neutrophil cytoplasmic antibody|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. <ref name="pmid27596099">{{cite journal| author=Noone D, Hebert D, Licht C| title=Pathogenesis and treatment of ANCA-associated vasculitis-a role for complement. | journal=Pediatr Nephrol | year= 2016 | volume=  | issue=  | pages=  | pmid=27596099 | doi=10.1007/s00467-016-3475-5 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27596099  }}</ref>
* The presence of [[Anti-neutrophil cytoplasmic antibody|ANCA]], induces [[Interleukin 23|Interleukin 23 (Il-23)]] to produce T helper 17 cells. The production of T helper 17 cells promotes the production of Il-17, [[Interleukin 6|IL-6]], and [[Tumor necrosis factor alpha|tumor necrosis factor alpha (TNF-α)]] which invokes the inflammation of cytokines. <ref name="pmid27596099">{{cite journal| author=Noone D, Hebert D, Licht C| title=Pathogenesis and treatment of ANCA-associated vasculitis-a role for complement. | journal=Pediatr Nephrol | year= 2016 | volume=  | issue=  | pages=  | pmid=27596099 | doi=10.1007/s00467-016-3475-5 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27596099  }}</ref>


=== Neutrophil activation ===
=== Neutrophil activation ===
* 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.
* The [[inflammation]] due to [[Cytokine|cytokines]] and the presence of [[Anti-neutrophil cytoplasmic antibody|ANCA]] allows [[Neutrophil|neutrophils]] to bind [[Tumor necrosis factor-alpha|TNFα]] that are actively present on the [[endothelium]], [[Anti-neutrophil cytoplasmic antibody|ANCA]] can cause [[Neutrophil|neutrophils]] to become active.
* This is due to Fragment secondary antibodies of ANCA that bind to proteinase 3 or myeloperoxidase.
* This is due to fragment secondary [[antibodies]] of [[Anti-neutrophil cytoplasmic antibody|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. <ref name="pmid16126939">{{cite journal| author=van Rossum AP, Limburg PC, Kallenberg CG| title=Activation, apoptosis, and clearance of neutrophils in Wegener's granulomatosis. | journal=Ann N Y Acad Sci | year= 2005 | volume= 1051 | issue=  | pages= 1-11 | pmid=16126939 | doi=10.1196/annals.1361.041 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16126939  }}</ref>
* The Fragment crystallizable (Fc) binds to the Fragment crystallizable- gamma receptor (Fc-γ) which allows [[Neutrophil|neutrophils]] to become active. With this activation, the [[endothelium]] becomes destroyed. This is due to [[degranulation]] and [[reactive oxygen species]]. <ref name="pmid16126939">{{cite journal| author=van Rossum AP, Limburg PC, Kallenberg CG| title=Activation, apoptosis, and clearance of neutrophils in Wegener's granulomatosis. | journal=Ann N Y Acad Sci | year= 2005 | volume= 1051 | issue=  | pages= 1-11 | pmid=16126939 | doi=10.1196/annals.1361.041 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16126939  }}</ref>


==Genetics==
==Genetics==
* The genetic component of Granulomatosis with polyangiitis is not fully known.  
* 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.<ref name="pmid23740775">{{cite journal| author=Xie G, Roshandel D, Sherva R, Monach PA, Lu EY, Kung T et al.| title=Association of granulomatosis with polyangiitis (Wegener's) with HLA-DPB1*04 and SEMA6A gene variants: evidence from genome-wide analysis. | journal=Arthritis Rheum | year= 2013 | volume= 65 | issue= 9 | pages= 2457-68 | pmid=23740775 | doi=10.1002/art.38036 | pmc=4471994 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23740775  }} </ref>
* However, there seems to be a strong correlation between HLA-DPB1 and HLA-DPB2 with granulomatosis with polyangiitis.<ref name="pmid23740775">{{cite journal| author=Xie G, Roshandel D, Sherva R, Monach PA, Lu EY, Kung T et al.| title=Association of granulomatosis with polyangiitis (Wegener's) with HLA-DPB1*04 and SEMA6A gene variants: evidence from genome-wide analysis. | journal=Arthritis Rheum | year= 2013 | volume= 65 | issue= 9 | pages= 2457-68 | pmid=23740775 | doi=10.1002/art.38036 | pmc=4471994 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23740775  }} </ref>
** HLA-DP1*401 is the strongest predictor especially when associated with [[ANCA]].<ref>https://ghr.nlm.nih.gov/condition/granulomatosis-with-polyangiitis#sourcesforpage</ref><ref name="pmid14968360">{{cite journal |vauthors=Jagiello P, Gencik M, Arning L, Wieczorek S, Kunstmann E, Csernok E, Gross WL, Epplen JT |title=New genomic region for Wegener's granulomatosis as revealed by an extended association screen with 202 apoptosis-related genes |journal=Hum. Genet. |volume=114 |issue=5 |pages=468–77 |date=April 2004 |pmid=14968360 |doi=10.1007/s00439-004-1092-z |url=}}</ref>
** HLA-DP1*401 is the strongest predictor especially when associated with [[ANCA]].<ref>https://ghr.nlm.nih.gov/condition/granulomatosis-with-polyangiitis#sourcesforpage</ref><ref name="pmid14968360">{{cite journal |vauthors=Jagiello P, Gencik M, Arning L, Wieczorek S, Kunstmann E, Csernok E, Gross WL, Epplen JT |title=New genomic region for Wegener's granulomatosis as revealed by an extended association screen with 202 apoptosis-related genes |journal=Hum. Genet. |volume=114 |issue=5 |pages=468–77 |date=April 2004 |pmid=14968360 |doi=10.1007/s00439-004-1092-z |url=}}</ref>
* The genetic inheritance of Granulomatosis with polyangiitis is not common.<ref name="pmid18163522">{{cite journal| author=Knight A, Sandin S, Askling J| title=Risks and relative risks of Wegener's granulomatosis among close relatives of patients with the disease. | journal=Arthritis Rheum | year= 2008 | volume= 58 | issue= 1 | pages= 302-7 | pmid=18163522 | doi=10.1002/art.23157 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18163522  }} </ref>
* The genetic inheritance of Granulomatosis with polyangiitis is not common.<ref name="pmid18163522">{{cite journal| author=Knight A, Sandin S, Askling J| title=Risks and relative risks of Wegener's granulomatosis among close relatives of patients with the disease. | journal=Arthritis Rheum | year= 2008 | volume= 58 | issue= 1 | pages= 302-7 | pmid=18163522 | doi=10.1002/art.23157 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18163522  }} </ref>
Line 35: Line 35:
== Associated Conditions ==
== Associated Conditions ==
The following conditions are associated with Granulomatosis with polyangiitis:
The following conditions are associated with Granulomatosis with polyangiitis:
* Subacute Infective Endocarditis<ref name="pmid26817911">{{cite journal| author=Langlois V, Lesourd A, Girszyn N, Ménard JF, Levesque H, Caron F et al.| title=Antineutrophil Cytoplasmic Antibodies Associated With Infective Endocarditis. | journal=Medicine (Baltimore) | year= 2016 | volume= 95 | issue= 3 | pages= e2564 | pmid=26817911 | doi=10.1097/MD.0000000000002564 | pmc=4998285 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26817911  }}</ref>  
* Subacute infective endocarditis<ref name="pmid26817911">{{cite journal| author=Langlois V, Lesourd A, Girszyn N, Ménard JF, Levesque H, Caron F et al.| title=Antineutrophil Cytoplasmic Antibodies Associated With Infective Endocarditis. | journal=Medicine (Baltimore) | year= 2016 | volume= 95 | issue= 3 | pages= e2564 | pmid=26817911 | doi=10.1097/MD.0000000000002564 | pmc=4998285 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26817911  }}</ref>  
* Goodpasture syndrome<ref name="pmid9355084">{{cite journal| author=Kalluri R, Meyers K, Mogyorosi A, Madaio MP, Neilson EG| title=Goodpasture syndrome involving overlap with Wegener's granulomatosis and anti-glomerular basement membrane disease. | journal=J Am Soc Nephrol | year= 1997 | volume= 8 | issue= 11 | pages= 1795-800 | pmid=9355084 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9355084  }}</ref>
* [[Goodpasture syndrome]]<ref name="pmid9355084">{{cite journal| author=Kalluri R, Meyers K, Mogyorosi A, Madaio MP, Neilson EG| title=Goodpasture syndrome involving overlap with Wegener's granulomatosis and anti-glomerular basement membrane disease. | journal=J Am Soc Nephrol | year= 1997 | volume= 8 | issue= 11 | pages= 1795-800 | pmid=9355084 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9355084  }}</ref>


==Gross Pathology==
==Gross Pathology==
*On gross pathology, following are non specific findings in Granulomatosis with polyangiitis:<ref name="pmid13560836">{{cite journal| author=WALTON EW| title=Giant-cell granuloma of the respiratory tract (Wegener's granulomatosis). | journal=Br Med J | year= 1958 | volume= 2 | issue= 5091 | pages= 265-70 | pmid=13560836 | doi= | pmc=2026251 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=13560836  }}</ref>  
*On gross pathology, following are non specific findings in Granulomatosis with polyangiitis:<ref name="pmid13560836">{{cite journal| author=WALTON EW| title=Giant-cell granuloma of the respiratory tract (Wegener's granulomatosis). | journal=Br Med J | year= 1958 | volume= 2 | issue= 5091 | pages= 265-70 | pmid=13560836 | doi= | pmc=2026251 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=13560836  }}</ref>  
**[[Ulceration]],
**[[Ulceration]]
**[[Necrosis]] of [[bone]] and [[cartilage]], and
**[[Necrosis]] of [[bone]] and [[cartilage]]
**Vascular [[necrosis]]
**Vascular [[necrosis]]
<gallery>
<gallery>


File:Gross Pathology Image Granulomatosis with polyangiitis.jpg|thumb|Granulomatosis with polyangiitis-Case courtesy of Dr. Yale Rosen<ref name="Gross pathology of Granulomatosis with polyangiitis">Case courtesy of Dr. Yale Rosen. https://radiopaedia.org/cases/8950 Accessed on March 29, 2018 </ref>
File:Gross Pathology Image Granulomatosis with polyangiitis.jpg|thumb|Granulomatosis with polyangiitis-Case courtesy of Dr. Yale Rosen<ref name="Gross pathology of Granulomatosis with polyangiitis">Case courtesy of Dr. Yale Rosen. https://radiopaedia.org/cases/8950 Accessed on March 29, 2018 </ref>
File:Wegeners granulomatosis (5187002087).jpg|thumb|Granulomatosis with polyangiitis- By Yale Rosen from USA <ref>(Wegener's granulomatosis  Uploaded by CFCF) [CC BY-SA 2.0 (https://creativecommons.org/licenses/by-sa/2.0)]</ref>


</gallery>
</gallery>
Line 51: Line 53:
==Microscopic Pathology==
==Microscopic Pathology==
*On microscopic histopathology analysis,the characteristic findings of GPA are:are characteristic findings of Granulomatosis with polyangiitis.<ref name="pmid1975173">{{cite journal| author=Lie JT| title=Illustrated histopathologic classification criteria for selected vasculitis syndromes. American College of Rheumatology Subcommittee on Classification of Vasculitis. | journal=Arthritis Rheum | year= 1990 | volume= 33 | issue= 8 | pages= 1074-87 | pmid=1975173 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1975173  }} </ref><ref name="pmid25076302">{{cite journal| author=Muller K, Lin JH| title=Orbital granulomatosis with polyangiitis (Wegener granulomatosis): clinical and pathologic findings. | journal=Arch Pathol Lab Med | year= 2014 | volume= 138 | issue= 8 | pages= 1110-4 | pmid=25076302 | doi=10.5858/arpa.2013-0006-RS | pmc=4140401 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25076302  }} </ref>
*On microscopic histopathology analysis,the characteristic findings of GPA are:are characteristic findings of Granulomatosis with polyangiitis.<ref name="pmid1975173">{{cite journal| author=Lie JT| title=Illustrated histopathologic classification criteria for selected vasculitis syndromes. American College of Rheumatology Subcommittee on Classification of Vasculitis. | journal=Arthritis Rheum | year= 1990 | volume= 33 | issue= 8 | pages= 1074-87 | pmid=1975173 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1975173  }} </ref><ref name="pmid25076302">{{cite journal| author=Muller K, Lin JH| title=Orbital granulomatosis with polyangiitis (Wegener granulomatosis): clinical and pathologic findings. | journal=Arch Pathol Lab Med | year= 2014 | volume= 138 | issue= 8 | pages= 1110-4 | pmid=25076302 | doi=10.5858/arpa.2013-0006-RS | pmc=4140401 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25076302  }} </ref>
**Focal and segmental necrotizing glomerulitis,
**Focal and segmental necrotizing glomerulitis
**Presence of non-caseating granuloma,
**Presence of non-caseating granuloma
**Necrotizing vasculitis,
**Necrotizing vasculitis
**Varied multinucleated giant cells at times  
**Varied [[multinucleated giant cells]] at times  
<gallery>
<gallery>
File:Granulomatosis with polyangiitis.jpg|thumb|Granulomatosis with polyangiitis.jpg<ref name="Granulomatosis with polyangiitis">Libre pathology. https://librepathology.org/wiki/Granulomatosis_with_polyangiitis Accessed on March 29, 2018</ref>
File:Granulomatosis with polyangiitis.jpg|thumb|Granulomatosis with polyangiitis<ref name="Granulomatosis with polyangiitis">Libre pathology. https://librepathology.org/wiki/Granulomatosis_with_polyangiitis Accessed on March 29, 2018</ref>
</gallery>
</gallery>


Latest revision as of 15:23, 16 April 2018

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: Amandeep Singh M.D.[3]Krzysztof Wierzbicki M.D. [4]Cafer Zorkun, M.D., Ph.D. [5]Amandeep Singh M.D.[6]

Overview

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.

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.

Role of bacterial antigens

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.[2]

Dysfunction of T regulator cells

Neutrophil activation

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.[5]
    • HLA-DP1*401 is the strongest predictor especially when associated with ANCA.[6][7]
  • The genetic inheritance of Granulomatosis with polyangiitis is not common.[8]

Associated Conditions

The following conditions are associated with Granulomatosis with polyangiitis:

Gross Pathology

  • Granulomatosis with polyangiitis-Case courtesy of Dr. Yale Rosen[12]

    Granulomatosis with polyangiitis-Case courtesy of Dr. Yale Rosen[12]

  • Granulomatosis with polyangiitis- By Yale Rosen from USA [13]

    Granulomatosis with polyangiitis- By Yale Rosen from USA [13]

Microscopic Pathology

  • On microscopic histopathology analysis,the characteristic findings of GPA are:are characteristic findings of Granulomatosis with polyangiitis.[14][15]
    • Focal and segmental necrotizing glomerulitis
    • Presence of non-caseating granuloma
    • Necrotizing vasculitis
    • Varied multinucleated giant cells at times
  • Granulomatosis with polyangiitis[16]

    Granulomatosis with polyangiitis[16]

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. ↑ Noone D, Hebert D, Licht C (2016). "Pathogenesis and treatment of ANCA-associated vasculitis-a role for complement". Pediatr Nephrol.   ( ):  . doi:10.1007/s00467-016-3475-5. PMID 27596099.
  4. ↑ van Rossum AP, Limburg PC, Kallenberg CG (2005). "Activation, apoptosis, and clearance of neutrophils in Wegener's granulomatosis". Ann N Y Acad Sci. 1051 ( ): 1–11. doi:10.1196/annals.1361.041. PMID 16126939.
  5. ↑ 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.
  6. ↑ https://ghr.nlm.nih.gov/condition/granulomatosis-with-polyangiitis#sourcesforpage
  7. ↑ Jagiello P, Gencik M, Arning L, Wieczorek S, Kunstmann E, Csernok E, Gross WL, Epplen JT (April 2004). "New genomic region for Wegener's granulomatosis as revealed by an extended association screen with 202 apoptosis-related genes". Hum. Genet. 114 (5): 468–77. doi:10.1007/s00439-004-1092-z. PMID 14968360.
  8. ↑ Knight A, Sandin S, Askling J (2008). "Risks and relative risks of Wegener's granulomatosis among close relatives of patients with the disease". Arthritis Rheum. 58 (1): 302–7. doi:10.1002/art.23157. PMID 18163522.
  9. ↑ Langlois V, Lesourd A, Girszyn N, Ménard JF, Levesque H, Caron F; et al. (2016). "Antineutrophil Cytoplasmic Antibodies Associated With Infective Endocarditis". Medicine (Baltimore). 95 (3): e2564. doi:10.1097/MD.0000000000002564. PMC 4998285. PMID 26817911.
  10. ↑ Kalluri R, Meyers K, Mogyorosi A, Madaio MP, Neilson EG (1997). "Goodpasture syndrome involving overlap with Wegener's granulomatosis and anti-glomerular basement membrane disease". J Am Soc Nephrol. 8 (11): 1795–800. PMID 9355084.
  11. ↑ WALTON EW (1958). "Giant-cell granuloma of the respiratory tract (Wegener's granulomatosis)". Br Med J. 2 (5091): 265–70. PMC 2026251. PMID 13560836.
  12. ↑ Case courtesy of Dr. Yale Rosen. https://radiopaedia.org/cases/8950 Accessed on March 29, 2018
  13. ↑ (Wegener's granulomatosis Uploaded by CFCF) [CC BY-SA 2.0 (https://creativecommons.org/licenses/by-sa/2.0)]
  14. ↑ Lie JT (1990). "Illustrated histopathologic classification criteria for selected vasculitis syndromes. American College of Rheumatology Subcommittee on Classification of Vasculitis". Arthritis Rheum. 33 (8): 1074–87. PMID 1975173.
  15. ↑ 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.
  16. ↑ Libre pathology. https://librepathology.org/wiki/Granulomatosis_with_polyangiitis Accessed on March 29, 2018

Template:WikiDoc Sources

Retrieved from "https://www.wikidoc.org/index.php?title=Granulomatosis_with_polyangiitis_pathophysiology&oldid=1462965"