BACKGROUND: C4d assessment of endomyocardial biopsies (EMBs) after heart transplantation (HTx) has been widely adopted to aid in the diagnosis of antibody-mediated rejection (AMR), yet it remains unclear whether or not to assess all patients routinely and with what frequency/duration. In this study we sought to evaluate the utility of routine C4d immunostaining in the first year after pediatric and young adult HTx. METHODS: We reviewed pre-transplant alloantibody and clinical data, including serial EMB reports, on all 51 patients who received HTx at our center since we instituted routine C4d staining of all first-year EMBs. C4d was considered positive if diffuse capillary staining (≥ 2(+)) was present. Rare/focal capillary staining or absence of staining was considered negative. RESULTS: Twenty-six of 406 first-year EMBs (6%) were C4d(+) in 6 (12%) patients. Sixty-five percent of all C4d(+) EMBs occurred by 30 days post-transplant. Five of 6 patients had pre-transplant donor-specific antibody (DSA) ≥ 4,000 MFI. The sixth patient had neither pre-transplant anti-HLA antibodies nor a positive donor-specific cytotoxicity crossmatch (DSXM), but there was clinical concern for AMR. Among the entire cohort, 5 of 10 patients with pre-transplant DSA ≥ 4,000 MFI and/or a positive DSXM were C4d(+) compared with only 1 of 41 without (50% vs 2%; p = 0.001). CONCLUSIONS: In the first year after HTx, C4d(+) occurred early and only in children and young adults with pre-transplant DSA or with clinical suspicion of AMR. Although our data suggest that assessment limited to the first 90 days post-transplant in patients with pre-transplant DSA ≥ 4,000 MFI may be appropriate in the absence of clinical concern for AMR, further research is needed to determine the optimum strategy for post-transplant surveillance.
BACKGROUND: C4d assessment of endomyocardial biopsies (EMBs) after heart transplantation (HTx) has been widely adopted to aid in the diagnosis of antibody-mediated rejection (AMR), yet it remains unclear whether or not to assess all patients routinely and with what frequency/duration. In this study we sought to evaluate the utility of routine C4d immunostaining in the first year after pediatric and young adult HTx. METHODS: We reviewed pre-transplant alloantibody and clinical data, including serial EMB reports, on all 51 patients who received HTx at our center since we instituted routine C4d staining of all first-year EMBs. C4d was considered positive if diffuse capillary staining (≥ 2(+)) was present. Rare/focal capillary staining or absence of staining was considered negative. RESULTS: Twenty-six of 406 first-year EMBs (6%) were C4d(+) in 6 (12%) patients. Sixty-five percent of all C4d(+) EMBs occurred by 30 days post-transplant. Five of 6 patients had pre-transplant donor-specific antibody (DSA) ≥ 4,000 MFI. The sixth patient had neither pre-transplant anti-HLA antibodies nor a positive donor-specific cytotoxicity crossmatch (DSXM), but there was clinical concern for AMR. Among the entire cohort, 5 of 10 patients with pre-transplant DSA ≥ 4,000 MFI and/or a positive DSXM were C4d(+) compared with only 1 of 41 without (50% vs 2%; p = 0.001). CONCLUSIONS: In the first year after HTx, C4d(+) occurred early and only in children and young adults with pre-transplant DSA or with clinical suspicion of AMR. Although our data suggest that assessment limited to the first 90 days post-transplant in patients with pre-transplant DSA ≥ 4,000 MFI may be appropriate in the absence of clinical concern for AMR, further research is needed to determine the optimum strategy for post-transplant surveillance.
Authors: Susan Stewart; Gayle L Winters; Michael C Fishbein; Henry D Tazelaar; Jon Kobashigawa; Jacki Abrams; Claus B Andersen; Annalisa Angelini; Gerald J Berry; Margaret M Burke; Anthony J Demetris; Elizabeth Hammond; Silviu Itescu; Charles C Marboe; Bruce McManus; Elaine F Reed; Nancy L Reinsmoen; E Rene Rodriguez; Alan G Rose; Marlene Rose; Nicole Suciu-Focia; Adriana Zeevi; Margaret E Billingham Journal: J Heart Lung Transplant Date: 2005-06-20 Impact factor: 10.247
Authors: Abdallah G Kfoury; M Elizabeth H Hammond; Gregory L Snow; Josef Stehlik; Bruce B Reid; James W Long; Edward M Gilbert; Feras M Bader; David A Bull; Dale G Renlund Journal: J Heart Lung Transplant Date: 2007-11-26 Impact factor: 10.247
Authors: E R Rodriguez; Diane V Skojec; Carmela D Tan; Andrea A Zachary; Edward K Kasper; John V Conte; William M Baldwin Journal: Am J Transplant Date: 2005-11 Impact factor: 8.086
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 Journal: Kidney Int Date: 2012-02-01 Impact factor: 10.612
Authors: Abdallah G Kfoury; M Elizabeth H Hammond; Gregory L Snow; Stavros G Drakos; Josef Stehlik; Patrick W Fisher; Bruce B Reid; Melanie D Everitt; Feras M Bader; Dale G Renlund Journal: J Heart Lung Transplant Date: 2009-08 Impact factor: 10.247
Authors: E H Hammond; R L Yowell; S Nunoda; R L Menlove; D G Renlund; M R Bristow; W A Gay; K W Jones; J B O'Connell Journal: J Heart Transplant Date: 1989 Nov-Dec