Utility of Routine Immunofluorescence Staining for C4d in Cardiac Transplant Recipients

Sachin Gupta, Joshua D. Mitchell, Bhavna Lavingia, Gene E. Ewing, M. Nicholas Feliciano, Patricia A. Kaiser, W. Steves Ring, Peter Stastny, Parag C. Patel, David W. Markham, Pradeep P A Mammen, J. Michael DiMaio, Mark H. Drazner

Research output: Contribution to journalArticle

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Abstract

Background: Immunofluorescence staining of endomyocardial biopsy (EMB) specimens to detect the complement fragment C4d is used to diagnose antibody-mediated rejection. However, data are limited regarding the utility of routine staining for C4d in clinical care. Methods: This study retrospectively reviewed the clinical course of adult cardiac transplant recipients who underwent ≥ 2 EMBs with immunofluorescence C4d staining at the University of Texas Southwestern Medical Center since September 2006. C4d staining was performed by the immunohistochemistry laboratory and interpreted by the members of the surgical pathology department, in conjunction with interpretation of the routine hematoxylin and eosin staining. Donor-specific antibodies (DSA) were routinely assessed at the time of clinical rejection. Results: Of 67 patients, specimens were positive for C4d (C4d+) in 14 and negative for C4d (C4d-) in 53. The frequency of acute cellular rejection (ACR) in these 2 groups was 57% (8 of 14, designated C4d+/ACR+) vs 11% (6 of 53, designated C4d-/ACR+; p < 0.001). Significantly more patients with a positive C4d specimen had a positive retrospective donor specific crossmatch, presence of DSA after transplantation, and depressed graft function (p < 0.01 for each). Conclusions: Positive C4d immunofluorescence staining on EMB specimens was associated with ACR, reduced allograft function, a positive retrospective crossmatch, and the presence of DSA after transplantation. The latter 2 observations support the contention that C4d deposition is a marker of antibody-mediated rejection. Routine evaluation of C4d staining is feasible in the clinical setting and may identify variable patterns of rejection.

Original languageEnglish (US)
Pages (from-to)776-780
Number of pages5
JournalJournal of Heart and Lung Transplantation
Volume28
Issue number8
DOIs
StatePublished - Aug 2009

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Fluorescent Antibody Technique
Staining and Labeling
Tissue Donors
Antibodies
Transplantation
Biopsy
Surgical Pathology
Hematoxylin
Eosine Yellowish-(YS)
Transplant Recipients
Allografts
Immunohistochemistry
Transplants

ASJC Scopus subject areas

  • Transplantation
  • Cardiology and Cardiovascular Medicine
  • Pulmonary and Respiratory Medicine
  • Surgery

Cite this

Utility of Routine Immunofluorescence Staining for C4d in Cardiac Transplant Recipients. / Gupta, Sachin; Mitchell, Joshua D.; Lavingia, Bhavna; Ewing, Gene E.; Feliciano, M. Nicholas; Kaiser, Patricia A.; Ring, W. Steves; Stastny, Peter; Patel, Parag C.; Markham, David W.; Mammen, Pradeep P A; DiMaio, J. Michael; Drazner, Mark H.

In: Journal of Heart and Lung Transplantation, Vol. 28, No. 8, 08.2009, p. 776-780.

Research output: Contribution to journalArticle

Gupta, S, Mitchell, JD, Lavingia, B, Ewing, GE, Feliciano, MN, Kaiser, PA, Ring, WS, Stastny, P, Patel, PC, Markham, DW, Mammen, PPA, DiMaio, JM & Drazner, MH 2009, 'Utility of Routine Immunofluorescence Staining for C4d in Cardiac Transplant Recipients', Journal of Heart and Lung Transplantation, vol. 28, no. 8, pp. 776-780. https://doi.org/10.1016/j.healun.2009.05.007
Gupta, Sachin ; Mitchell, Joshua D. ; Lavingia, Bhavna ; Ewing, Gene E. ; Feliciano, M. Nicholas ; Kaiser, Patricia A. ; Ring, W. Steves ; Stastny, Peter ; Patel, Parag C. ; Markham, David W. ; Mammen, Pradeep P A ; DiMaio, J. Michael ; Drazner, Mark H. / Utility of Routine Immunofluorescence Staining for C4d in Cardiac Transplant Recipients. In: Journal of Heart and Lung Transplantation. 2009 ; Vol. 28, No. 8. pp. 776-780.
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abstract = "Background: Immunofluorescence staining of endomyocardial biopsy (EMB) specimens to detect the complement fragment C4d is used to diagnose antibody-mediated rejection. However, data are limited regarding the utility of routine staining for C4d in clinical care. Methods: This study retrospectively reviewed the clinical course of adult cardiac transplant recipients who underwent ≥ 2 EMBs with immunofluorescence C4d staining at the University of Texas Southwestern Medical Center since September 2006. C4d staining was performed by the immunohistochemistry laboratory and interpreted by the members of the surgical pathology department, in conjunction with interpretation of the routine hematoxylin and eosin staining. Donor-specific antibodies (DSA) were routinely assessed at the time of clinical rejection. Results: Of 67 patients, specimens were positive for C4d (C4d+) in 14 and negative for C4d (C4d-) in 53. The frequency of acute cellular rejection (ACR) in these 2 groups was 57{\%} (8 of 14, designated C4d+/ACR+) vs 11{\%} (6 of 53, designated C4d-/ACR+; p < 0.001). Significantly more patients with a positive C4d specimen had a positive retrospective donor specific crossmatch, presence of DSA after transplantation, and depressed graft function (p < 0.01 for each). Conclusions: Positive C4d immunofluorescence staining on EMB specimens was associated with ACR, reduced allograft function, a positive retrospective crossmatch, and the presence of DSA after transplantation. The latter 2 observations support the contention that C4d deposition is a marker of antibody-mediated rejection. Routine evaluation of C4d staining is feasible in the clinical setting and may identify variable patterns of rejection.",
author = "Sachin Gupta and Mitchell, {Joshua D.} and Bhavna Lavingia and Ewing, {Gene E.} and Feliciano, {M. Nicholas} and Kaiser, {Patricia A.} and Ring, {W. Steves} and Peter Stastny and Patel, {Parag C.} and Markham, {David W.} and Mammen, {Pradeep P A} and DiMaio, {J. Michael} and Drazner, {Mark H.}",
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T1 - Utility of Routine Immunofluorescence Staining for C4d in Cardiac Transplant Recipients

AU - Gupta, Sachin

AU - Mitchell, Joshua D.

AU - Lavingia, Bhavna

AU - Ewing, Gene E.

AU - Feliciano, M. Nicholas

AU - Kaiser, Patricia A.

AU - Ring, W. Steves

AU - Stastny, Peter

AU - Patel, Parag C.

AU - Markham, David W.

AU - Mammen, Pradeep P A

AU - DiMaio, J. Michael

AU - Drazner, Mark H.

PY - 2009/8

Y1 - 2009/8

N2 - Background: Immunofluorescence staining of endomyocardial biopsy (EMB) specimens to detect the complement fragment C4d is used to diagnose antibody-mediated rejection. However, data are limited regarding the utility of routine staining for C4d in clinical care. Methods: This study retrospectively reviewed the clinical course of adult cardiac transplant recipients who underwent ≥ 2 EMBs with immunofluorescence C4d staining at the University of Texas Southwestern Medical Center since September 2006. C4d staining was performed by the immunohistochemistry laboratory and interpreted by the members of the surgical pathology department, in conjunction with interpretation of the routine hematoxylin and eosin staining. Donor-specific antibodies (DSA) were routinely assessed at the time of clinical rejection. Results: Of 67 patients, specimens were positive for C4d (C4d+) in 14 and negative for C4d (C4d-) in 53. The frequency of acute cellular rejection (ACR) in these 2 groups was 57% (8 of 14, designated C4d+/ACR+) vs 11% (6 of 53, designated C4d-/ACR+; p < 0.001). Significantly more patients with a positive C4d specimen had a positive retrospective donor specific crossmatch, presence of DSA after transplantation, and depressed graft function (p < 0.01 for each). Conclusions: Positive C4d immunofluorescence staining on EMB specimens was associated with ACR, reduced allograft function, a positive retrospective crossmatch, and the presence of DSA after transplantation. The latter 2 observations support the contention that C4d deposition is a marker of antibody-mediated rejection. Routine evaluation of C4d staining is feasible in the clinical setting and may identify variable patterns of rejection.

AB - Background: Immunofluorescence staining of endomyocardial biopsy (EMB) specimens to detect the complement fragment C4d is used to diagnose antibody-mediated rejection. However, data are limited regarding the utility of routine staining for C4d in clinical care. Methods: This study retrospectively reviewed the clinical course of adult cardiac transplant recipients who underwent ≥ 2 EMBs with immunofluorescence C4d staining at the University of Texas Southwestern Medical Center since September 2006. C4d staining was performed by the immunohistochemistry laboratory and interpreted by the members of the surgical pathology department, in conjunction with interpretation of the routine hematoxylin and eosin staining. Donor-specific antibodies (DSA) were routinely assessed at the time of clinical rejection. Results: Of 67 patients, specimens were positive for C4d (C4d+) in 14 and negative for C4d (C4d-) in 53. The frequency of acute cellular rejection (ACR) in these 2 groups was 57% (8 of 14, designated C4d+/ACR+) vs 11% (6 of 53, designated C4d-/ACR+; p < 0.001). Significantly more patients with a positive C4d specimen had a positive retrospective donor specific crossmatch, presence of DSA after transplantation, and depressed graft function (p < 0.01 for each). Conclusions: Positive C4d immunofluorescence staining on EMB specimens was associated with ACR, reduced allograft function, a positive retrospective crossmatch, and the presence of DSA after transplantation. The latter 2 observations support the contention that C4d deposition is a marker of antibody-mediated rejection. Routine evaluation of C4d staining is feasible in the clinical setting and may identify variable patterns of rejection.

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