Editing Transplant rejection (section)

===Chronic rejection===
[[Image:Transplant glomerulopathy - very high mag.jpg| thumb| [[Micrograph]] showing a [[glomerulus]] with changes characteristic of a transplant glomerulopathy. [[Transplant glomerulopathy]] is considered a form of chronic antibody-mediated rejection. [[PAS stain]].]]
'''Chronic rejection''' is an insidious form of rejection that leads to graft destruction over the course of months, but most often years after tissue transplantation.<ref name=":10" /> The mechanism for chronic rejection is yet to be fully understood, but it is known that prior acute rejection episodes are the main clinical predictor for the development of chronic rejection.<ref name=":2" /> In particular, the incidence increases following severe or persistent acute rejection, whereas acute rejection episodes with return to function back to baseline do not have major effects on graft survival.<ref name=":11">{{cite book | vauthors = Gautreaux MD | chapter = Chapter 17 - Histocompatibility Testing in the Transplant Setting |date=2017-01-01 | title = Kidney Transplantation, Bioengineering and Regeneration |pages=223–234 | veditors = Orlando G, Remuzzi G, Williams DF |publisher=Academic Press |language=en |doi=10.1016/b978-0-12-801734-0.00017-5 |isbn=978-0-12-801734-0 }}</ref><ref>{{cite book | vauthors = Srinivas TR, Schold JD, Meier-Kriesche HU | chapter = Chapter 105 - Outcomes of Renal Transplantation |date=2010-01-01 | title = Comprehensive Clinical Nephrology |pages=1222–1231 | veditors = Floege J, Johnson RJ, Feehally J |place=Philadelphia |publisher=Mosby |language=en |doi=10.1016/b978-0-323-05876-6.00105-2 |isbn=978-0-323-05876-6 | edition = Fourth }}</ref> Chronic rejection is generally thought of as being related to either vascular damage or parenchymal damage with subsequent fibrosis.<ref>{{cite book | vauthors = Dharnidharka VR | chapter = Chapter 43 - Pediatric Renal Transplantation |date=2019-01-01 |doi = 10.1016/B978-0-323-52978-5.00043-4 | title = Chronic Kidney Disease, Dialysis, and Transplantation | edition = Fourth |pages=661–675.e7 | veditors = Himmelfarb J, Ikizler TA |place=Philadelphia |publisher=Elsevier |language=en |isbn=978-0-323-52978-5 | s2cid = 81475473 }}</ref> While it is unknown the exact contribution of the immune system in these processes, the indirect pathway of allorecognition and the associated antibody formation seems to be especially involved.<ref name=":2" />

Chronic rejection has widely varied effects on different organs. At 5 years post-transplant, 80% of lung transplants, 60% of heart transplants and 50% of kidney transplants are affected, while liver transplants are only affected 10% of the time.<ref name=":11" /> Therefore, chronic rejection explains long-term morbidity in most lung-transplant recipients,<ref name="pmid15667618">{{cite journal | vauthors = Jaramillo A, Fernández FG, Kuo EY, Trulock EP, Patterson GA, Mohanakumar T | title = Immune mechanisms in the pathogenesis of bronchiolitis obliterans syndrome after lung transplantation | journal = Pediatric Transplantation | volume = 9 | issue = 1 | pages = 84–93 | date = February 2005 | pmid = 15667618 | doi = 10.1111/j.1399-3046.2004.00270.x | s2cid = 25841425 }}</ref><ref name="pmid14621118">{{cite journal | vauthors = Lau CL, Patterson GA | title = Current status of lung transplantation | journal = The European Respiratory Journal. Supplement | volume = 47 | pages = 57s–64s | date = November 2003 | pmid = 14621118 | doi = 10.1183/09031936.03.00022103 | doi-access = free }}</ref> the median survival roughly 4.7 years, about half the span versus other major organ transplants.<ref>{{cite web | title = Organ Procurement and Transplantation Network | work = U.S. Department of Health & Human Services | url = http://optn.transplant.hrsa.gov/ }}</ref> Airflow obstruction not ascribable to other cause is labeled [[bronchiolitis obliterans]] [[syndrome]] (BOS), confirmed by a persistent drop—three or more weeks—in ''forced expiratory volume'' (FEV<sub>1</sub>) by at least 20%.<ref name="pmid17347496">{{cite journal |display-authors=6 |vauthors=Lama VN, Murray S, Lonigro RJ, Toews GB, Chang A, Lau C, Flint A, Chan KM, Martinez FJ |date=June 2007 |title=Course of FEV(1) after onset of bronchiolitis obliterans syndrome in lung transplant recipients |journal=American Journal of Respiratory and Critical Care Medicine |volume=175 |issue=11 |pages=1192–1198 |doi=10.1164/rccm.200609-1344OC |pmc=1899272 |pmid=17347496}}</ref> First noted is infiltration by [[lymphocytes]], followed by [[epithelium|epithelial cell]] injury, then inflammatory lesions and recruitment of [[fibroblasts]] and [[myofibroblasts]], which proliferate and secrete proteins forming scar tissue.<ref name="pmid16799090">{{cite journal |vauthors=Nicod LP |date=July 2006 |title=Mechanisms of airway obliteration after lung transplantation |journal=Proceedings of the American Thoracic Society |volume=3 |issue=5 |pages=444–449 |doi=10.1513/pats.200601-007AW |pmid=16799090}}</ref> A similar phenomenon can be seen with liver transplant wherein fibrosis leads to jaundice secondary to the destruction of bile ducts within the liver, also known as vanishing bile duct syndrome.<ref>{{cite book | vauthors = Hübscher SG, Clouston AD | chapter = Chapter 15 - Transplantation pathology |date= January 2012 | doi =10.1016/B978-0-7020-3398-8.00015-5 | title = MacSween's Pathology of the Liver |pages=853–933 | veditors = Burt AD, Portmann BC, Ferrell LD |place=Edinburgh |publisher=Churchill Livingstone |language=en |isbn=978-0-7020-3398-8 | edition = Sixth }}</ref>