Goodpasture syndrome 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: Krzysztof Wierzbicki M.D. [3] Akshun Kalia M.B.B.S.[4]

Overview

The pathogenesis of Goodpasture syndrome includes the presence of autoantibodies directed against the glomerular and/or alveolar basement membrane. As with many autoimmune conditions, the precise cause of Goodpasture’s Syndrome is not yet known. It is believed to be a type II hypersensitivity reaction to Goodpasture’s antigens on the cells of the glomeruli of the kidneys and the pulmonary alveoli. The basement membrane (including a triple chain type IV collagen) lining the alveoli and glomeruli is particularly damaged in patients suffering from Goodpasture syndrome. The immune system misreads self-tissues as foreign, which leads to attack and destruction, as it would happen in case of an invading pathogen. The target antigen that is associated with the strongest pathogenic effect in anti-GBM disease is the non-collagenous 1 domain of alpha-3 type IV collagen. There is strong correlation of anti-glomerular basement membrane disease with allele HLA DRB1-1501. This allele is associated with renal injury. On gross pathology, Goodpasture syndrome with lung involvement may present with diffuse pulmonary hemorrhage. On microscopic histopathological analysis, early focal proliferative changes that display necrosis and crescent formation (due to hypercellular glomeruli) with an inflamed interstitium are seen. Under direct immunofluorescence, linear immunoglobulin G deposits are found encompassing the glomerular basement membrane and at times the distal tubular portion of the basement membrane.

Pathogenesis

Goodpasture syndrome is an autoimmune condition resulting from antibodies against the glomerular and alveolar basement membrane. It is thought that Goodpasture syndrome is the result of type II hypersensitivity reaction which leads to generation of antibodies which bind antigenic proteins of glomerular and alveolar basement membrane. The antigen-antibody complex leads to activation of complement system and tissue destruction.[1][2]

Anatomy

Renal corpuscle. (Source: [Michal Komorniczak (Poland)[CC BY-SA 3.0 (https://creativecommons.org/licenses/by-sa/3.0)], from Wikimedia Commons])
Alveolar wall ([By Cruithne9 [CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0)], from Wikimedia Commons])


The key for the renal corpuscle figure is: A – Renal corpuscle, B – Proximal tubule, C – Distal convoluted tubule, D – Juxtaglomerular apparatus, 1. Basement membrane (Basal lamina), 2. Bowman's capsule – parietal layer, 3. Bowman's capsule – visceral layer, 3a. Pedicels (Foot processes from podocytes), 3b. Podocyte, 4. Bowman's space (urinary space), 5a. Mesangium – Intraglomerular cell, 5b. Mesangium – Extraglomerular cell, 6. Granular cells (Juxtaglomerular cells), 7. Macula densa, 8. Myocytes (smooth muscle), 9. Afferent arteriole, 10. Glomerulus Capillaries, 11. Efferent arteriole.

Pathophysiology

Genes

Genes involved in the pathogenesis of Goodpasture syndrome include certain alleles of human leukocyte antigen (HLA).[2] [8]

  • HLA-B27 has been found to be more frequently associated with severe nephritic form of Goodpasture syndrome.
  • Other alleles associated with Goodpasture syndrome include increased frequency of HLA-DR15 and DRB1*03, DRB1*04 and a decreased frequency of DRB1*01 and DRB1*07.
  • Goodpasture disease is also strongly associated with the DRB1*1501 and to DRB1*1502 allele.
  • The allele DRB1*1501 is primarily associated with causing renal injury and estimated to be present in 80% of patients with Goodpasture syndrome,
  • Recent studies have shown that DRB1*1501 allele is found in approximately one third of Caucasian patients with Goodpasture syndrome.

Gross Pathology

On gross pathology, Goddpasture syndrome with lung involvement may present with diffuse pulmonary hemorrhage.

Diffuse pulmonary hemorrhage in Goodpasture syndrome ([Case ourtesy of Yale Rosen, MD https://www.flickr.com/photos/pulmonary_pathology/3731499661])

Microscopic Pathology

On microscopic histopathological analysis, findings include:[9][10][11][12]

  • The following are images of the microscopic pathology of crescent glomerulonephritis and the immunofluorescence of linear IgG and C3 deposition.
Crescentic glomerulonephritis ([By Nephron [CC BY-SA 3.0 (https://creativecommons.org/licenses/by-sa/3.0) or GFDL (http://www.gnu.org/copyleft/fdl.html)], from Wikimedia Commons])
Goodpasture Disease depicting linear IgG & C3 deposits around GBM. [13]


References

  1. 1.0 1.1 Zhao J, Cui Z, Yang R, Jia XY, Zhang Y, Zhao MH (November 2009). "Anti-glomerular basement membrane autoantibodies against different target antigens are associated with disease severity". Kidney Int. 76 (10): 1108–15. doi:10.1038/ki.2009.348. PMID 19741587.
  2. 2.0 2.1 Xie LJ, Cui Z, Jia XY, Chen Z, Liu XR, Zhao MH (July 2015). "Coexistence of Anti-Glomerular Basement Membrane Antibodies and Anti-Neutrophil Cytoplasmic Antibodies in a Child With Human Leukocyte Antigen Susceptibility and Detailed Antibody Description: A Case Report". Medicine (Baltimore). 94 (29): e1179. doi:10.1097/MD.0000000000001179. PMID 26200622.
  3. Chen JL, Hu SY, Jia XY, Zhao J, Yang R, Cui Z, Zhao MH (January 2013). "Association of epitope spreading of antiglomerular basement membrane antibodies and kidney injury". Clin J Am Soc Nephrol. 8 (1): 51–8. doi:10.2215/CJN.05140512. PMC 3531658. PMID 23085731.
  4. Hudson BG, Tryggvason K, Sundaramoorthy M, Neilson EG (June 2003). "Alport's syndrome, Goodpasture's syndrome, and type IV collagen". N. Engl. J. Med. 348 (25): 2543–56. doi:10.1056/NEJMra022296. PMID 12815141.
  5. Cui Z, Zhao J, Jia XY, Zhu SN, Zhao MH (April 2011). "Clinical features and outcomes of anti-glomerular basement membrane disease in older patients". Am. J. Kidney Dis. 57 (4): 575–82. doi:10.1053/j.ajkd.2010.09.022. PMID 21168945.
  6. Peto P, Salama AD (January 2011). "Update on antiglomerular basement membrane disease". Curr Opin Rheumatol. 23 (1): 32–7. doi:10.1097/BOR.0b013e328341009f. PMID 21124085.
  7. Pedchenko V, Bondar O, Fogo AB, Vanacore R, Voziyan P, Kitching AR, Wieslander J, Kashtan C, Borza DB, Neilson EG, Wilson CB, Hudson BG (July 2010). "Molecular architecture of the Goodpasture autoantigen in anti-GBM nephritis". N. Engl. J. Med. 363 (4): 343–54. doi:10.1056/NEJMoa0910500. PMC 4144421. PMID 20660402.
  8. Couser WG (2016). "Pathogenesis and treatment of glomerulonephritis-an update". J Bras Nefrol. 38 (1): 107–22. doi:10.5935/0101-2800.20160016. PMID 27049372.
  9. Frankel SK, Cosgrove GP, Fischer A, Meehan RT, Brown KK (February 2006). "Update in the diagnosis and management of pulmonary vasculitis". Chest. 129 (2): 452–65. doi:10.1378/chest.129.2.452. PMID 16478866.
  10. Zhao J, Yan Y, Cui Z, Yang R, Zhao MH (June 2009). "The immunoglobulin G subclass distribution of anti-GBM autoantibodies against rHalpha3(IV)NC1 is associated with disease severity". Hum. Immunol. 70 (6): 425–9. doi:10.1016/j.humimm.2009.04.004. PMID 19364515.
  11. University of Pittsburgh Medical Center Pathology. www.path.upmc.edu/cases/case541.html Accessed on Novermber 2nd 2016
  12. Greco A, Rizzo MI, De Virgilio A, Gallo A, Fusconi M, Pagliuca G; et al. (2015). "Goodpasture's syndrome: a clinical update". Autoimmun Rev. 14 (3): 246–53. doi:10.1016/j.autrev.2014.11.006. PMID 25462583.
  13. http://picasaweb.google.com/mcmumbi/USMLEIIImages

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