Literature DB >> 12919095

Use of C4d as a diagnostic adjunct in lung allograft biopsies.

Cynthia M Magro1, Amy Pope Harman, Dana Klinger, Charles Orosz, Patrick Adams, James Waldman, Deborah Knight, Moira Kelsey, Patrick Ross.   

Abstract

PURPOSE: Humoral allograft rejection is a defined mechanism for cardiac and renal graft dysfunction; C4d deposition, a stable component of complement activation, inversely correlates with graft survival. With the recent recognition of humoral rejection in lung grafts, we examined C4d's role as a prognostic adjunct in lung allografts.
MATERIAL AND METHODS: Twenty-three lung recipients underwent biopsies for deterioration in clinical status or routine surveillance. Clinically unwell patients possessed acute rejection or bronchiolitis obliterans syndrome (BOS). Biopsies attributable to infection were excluded from the study. In addition to routine light microscopy, an attempt was made to correlate the clinical status and morphologic findings with the pattern of C4d deposition and also to compare these clinical and morphologic parameters with the other assessed immunoreactants. Panel reactive antibody testing was also carried out at various points in their post transplantation course whereby in 6 of the cases the samples were procured at exactly the same time as the tissue samples.
RESULTS: The patients were segregated into two groups: those patients with recurrent acute rejection and those with BOS. In those patients with symptomatic acute rejection, all biopsies showed light microscopic and immunofluorescent evidence of humoral allograft rejection. The level of C4d was positively correlated with the degree of parenchymal injury, the hallmark being one of septal capillary necrosis. In addition, high and intermediate levels of C4d correlated with a clinical diagnosis of acute rejection. C4d was the strongest predictor of parenchymal injury and of the clinical status (p <.0001) compared to other the immunoreactants C1q, C5b-9 and immunoglobulin. There was no specific correlation between C4d deposition and the presence of acute cellular rejection. In those patients fulfilling clinical criteria of BOS, deposits of C4d as well as other immunoreactants were found in the bronchial wall as opposed to the rarity of this finding in bon-BOS patients. However the only statistically significant predictor of BOS was bronchial wall deposition of C1q. In no case were panel reactive antibodies at significant levels discovered post transplantation.
CONCLUSIONS: In the context of acute rejection, C4d deposition correlates with clinical evidence of rejection and the degree of humoral rejection assessed pathologically; there is no association with the presence of histocompatibility related antibodies. It is a more specific predictor of allograft status compared to other immunoreactants. C4d deposition within the bronchial wall is a feature of BOS and hence may be used as a marker of chronic graft dysfunction. The antigenic target resulting in C4d deposition may not be histocompatibility related.

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Year:  2003        PMID: 12919095     DOI: 10.1034/j.1600-6143.2003.00152.x

Source DB:  PubMed          Journal:  Am J Transplant        ISSN: 1600-6135            Impact factor:   8.086


  12 in total

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Review 2.  Autoantibody formation in human and rat studies of chronic rejection and primary graft dysfunction.

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Review 3.  Pros and cons for C4d as a biomarker.

Authors:  Danielle Cohen; Robert B Colvin; Mohamed R Daha; Cinthia B Drachenberg; Mark Haas; Volker Nickeleit; Jane E Salmon; Banu Sis; Ming-Hui Zhao; Jan A Bruijn; Ingeborg M Bajema
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4.  Increased erythrocyte C4D is associated with known alloantibody and autoantibody markers of antibody-mediated rejection in human lung transplant recipients.

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6.  IL-17-dependent cellular immunity to collagen type V predisposes to obliterative bronchiolitis in human lung transplants.

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Journal:  J Immunol       Date:  2015-12-15       Impact factor: 5.422

Review 9.  Humoral immunity and the development of obliterative bronchiolitis after lung transplantation: is there a link?

Authors:  Amir M Emtiazjoo; David S Wilkes
Journal:  Am J Respir Cell Mol Biol       Date:  2012-10-18       Impact factor: 6.914

10.  Activation of complement factor B contributes to murine and human myocardial ischemia/reperfusion injury.

Authors:  Nicholas Chun; Ala S Haddadin; Junying Liu; Yunfang Hou; Karen A Wong; Daniel Lee; Julie I Rushbrook; Karan Gulaya; Roberta Hines; Tamika Hollis; Beatriz Nistal Nuno; Abeel A Mangi; Sabet Hashim; Marcela Pekna; Amy Catalfamo; Hsiao-Ying Chin; Foramben Patel; Sravani Rayala; Ketan Shevde; Peter S Heeger; Ming Zhang
Journal:  PLoS One       Date:  2017-06-29       Impact factor: 3.240

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