Immunoperoxidase Staining for C4d on Paraffin-embedded Tissue in Cardiac Allograft Endomyocardial Biopsies

Chantranuwat, Chavit; Qiao, Jian-Hua; Kobashigawa, Jon A.; Li, Hong; Shintaku, Peter; Fishbein, Michael C.

doi:10.1097/00129039-200406000-00012

Cited by 67 publications

(50 citation statements)

References 9 publications

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“…Behr et al (13) found that among 56 patients, C4d in EMB samples taken within the first 3 months following transplant was associated with graft loss. Chantranuwat (20) has specifically claimed that immunoperoxidase staining of cardiac allograft EMB tissue for C4d is useful for diagnosis of HR.…”

Section: Discussionmentioning

confidence: 99%

Humoral Heart Rejection (Severe Allograft Dysfunction with no Signs of Cellular Rejection or Ischemia): Incidence, Management, and the Value of C4d for Diagnosis

Crespo‐Leiro¹,

Veiga‐Barreiro²,

Doménech

et al. 2005

American Journal of Transplantation

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Severe allograft dysfunction after heart transplant (HT), without ischemia or evidence of cellular rejection upon endomyocardial biopsy (EMB), is a rare but potentially fatal condition that suggests humoral rejection (HR). Its incidence, and the methods of choice for its diagnosis and management, remain uncertain. We retrospectively studied 445 HT patients (April 1991-December 2003) to determine incidence of HR diagnosed by clinical and conventional histopathological criteria. We used immunofluorescence (IF) techniques to test archived frozen EMB issue for IgM, IgG, C1q, C3, fibrin and C4d. Twelve patients (2.7%) fulfilled the criteria for HR after a mean time post-HT of 21.3 ± 24.7 months (range: 2-72 months). Patients were treated with high doses of steroids and plasmapheresis, with successful recovery in 11 cases. IF studies using classical markers were mainly negative for the six patients with enough EMB tissue for testing. All six patients showed positivity for C4d during the HR episode but not before or after. Humoral rejection was observed in less than 3% of HT patients. Plasmapheresis treatment was highly effective. Classical IF tests were not useful for diagnosis, but C4d appears to be useful both for confirmation of diagnosis and for monitoring response to treatment.

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Section: Discussionmentioning

confidence: 99%

Humoral Heart Rejection (Severe Allograft Dysfunction with no Signs of Cellular Rejection or Ischemia): Incidence, Management, and the Value of C4d for Diagnosis

Crespo‐Leiro¹,

Veiga‐Barreiro²,

Doménech

et al. 2005

American Journal of Transplantation

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“…[23][24][25] Currently, C4d is used frequently to diagnose AMR, and some authors suggest that C4d can be used as an immunopathologic surrogate for AMR. [25][26][27][28][29][30][31][32] C4d positivity is also used in combination with histological features-with circulating DSA, or clinical graft dysfunction. 23,[33][34][35][36] Depending on how restrictive the pathological definition of AMR is (ie, number of criteria required), the reported incidence varies, with lower reported incidence with more criteria required.…”

Section: Complement Componentsmentioning

confidence: 99%

Antibody-Mediated Rejection in Cardiac Transplantation: Emerging Knowledge in Diagnosis and Management

Colvin¹,

Cook²,

Chang³

et al. 2015

Circulation

274

251

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“…The subsequent availability of commercial monoclonal antibodies against complement split products C4d and C3d has proven the usefulness of these markers (6,7). Application of C4d staining alone gained wide acceptance when it was shown to work in formalin-fixed paraffinembedded tissue (8). To date, consensus does not exist in the methodology of detection of complement split products and their interpretation by pathologists.…”

Section: The Diagnosis Of Acute Antibody-mediated Rejection (Amr) In mentioning

confidence: 99%

“…Furthermore, there are only limited studies that correlate the presence of complement split products in the biopsy with circulating alloantibodies (7,9). [7][8][9], every 8 weeks for months [10][11][12], every 3 months for months [13][14][15][16][17][18][19][20][21][22][23][24], every 4 months for months [25][26][27][28][29][30][31][32][33][34][35][36] …”

Section: The Diagnosis Of Acute Antibody-mediated Rejection (Amr) In mentioning

confidence: 99%

Correlation of Donor-Specific Antibodies, Complement and Its Regulators with Graft Dysfunction in Cardiac Antibody-Mediated Rejection

Tan

Sokos²,

Pidwell³

et al. 2009

American Journal of Transplantation

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Antibody-mediated rejection (AMR) is an immunopathologic process in which activation of complement often results in allograft injury. This study correlates C4d and C3d with HLA serology and graft function as diagnostic criteria for AMR. Immunofluorescence staining for C4d and C3d was performed on 1511 biopsies from 330 patients as part of routine diagnostic work-up of rejection. Donor-specific antibodies were detected in 95% of those with C4d+C3d+ biopsies versus 35% in the C4d+C3d-group (p = 0.002). Allograft dysfunction was present in 84% in the C4d+ C3d+ group versus 5% in the C4d+C3d− group (p < 0.0001). Combined C4d and C3d positivity had a sensitivity of 100% and specificity of 99% for the pathologic diagnosis of AMR and a mortality of 37%. Since activation of complement does not always result in allograft dysfunction, we correlated the expression pattern of the complement regulators CD55 and CD59 in patients with and without complement deposition. The proportion of patients with CD55 and/or CD59 staining was highest in C4d+C3d− patients without allograft dysfunction (p = 0.03). We conclude that a panel of C4d and C3d is diagnostically more useful than C4d alone in the evaluation of AMR. CD55 and CD59 may play a protective role in patients with evidence of complement activation.

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Immunoperoxidase Staining for C4d on Paraffin-embedded Tissue in Cardiac Allograft Endomyocardial Biopsies

Cited by 67 publications

References 9 publications

Humoral Heart Rejection (Severe Allograft Dysfunction with no Signs of Cellular Rejection or Ischemia): Incidence, Management, and the Value of C4d for Diagnosis

Humoral Heart Rejection (Severe Allograft Dysfunction with no Signs of Cellular Rejection or Ischemia): Incidence, Management, and the Value of C4d for Diagnosis

Antibody-Mediated Rejection in Cardiac Transplantation: Emerging Knowledge in Diagnosis and Management

Correlation of Donor-Specific Antibodies, Complement and Its Regulators with Graft Dysfunction in Cardiac Antibody-Mediated Rejection

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