[353] Detection of C4D and C3D in Endomyocardial Biopsies at and Prior to Diagnosis of Antibody-Mediated Rejection

M Bhasin, MC Fishbein, EF Reed, JA Kobashigawa, CK Lai. David Geffen School of Medicine at UCLA, Los Angeles, CA

Background: C4d & C3d deposition in capillaries of cardiac allografts is associated with antibody-mediated rejection (AMR) & poor graft outcome. Both C4d & C3d immunostaining in endomyocardial biopsies (EMBs) at & prior to diagnosis of AMR have not been examined.
Design: EMBs from 7/97 to 9/05 of patients (pts) with AMR (diagnosed by histological findings & presence of intravascular CD68+ macrophages) & the immediate prior EMB without AMR were compared to EMBs from age- & sex-matched control group who never had AMR. All EMBs were stained with C4d & C3d via immunoperoxidase technique on paraffin-embedded sections. Fishers exact test was used for statistical analysis.
Results: The study group consisted of 89 pts (54 males & 35 females) with a mean age of 43.6 ± 21.1 years. Median time to first AMR biopsy was 197 days post transplant (DPT) (IQR = 1043 DPT). Median time to pre-AMR biopsy was 169 DPT (IQR = 791 DPT). The median pre-AMR to AMR interval was 31 DPT (IQR = 105 DPT). The control group consisted of 90 pts (55 males & 35 females) with mean age of 44.9 ± 20.7 years. Median time to EMB was 171 DPT (IQR = 10.8 DPT).

Table 1: C4d & C3d Staining Patterns for Control, Pre-AMR, & AMR Groups
GroupC4d StainingC3d Staining
GroupNegative (0+/1+)Positive (2+/3+)Negative (0+/1+)Positive (2+/3+)
Control88 (97.8%)2 (2.2%)86 (100%)0 (0%)
Pre-AMR66 (78.6%)18 (21.4%)74 (89.2%)9 (10.8%)
AMR56 (64.4%)31 (35.6%)72 (82.8%)15 (17.2%)




Joint C4d/C3d Staining Patterns for Control, Pre-AMR, and AMR Groups
GroupC4d+/C3d+C4d+/C3d-C4d-/C3d+C4d-/C3d-
Control0 (0%)2 (2.3%)0 (0%)84 (97.7%)
Pre-AMR9 (10.8%)9 (10.8%)0 (0%)65 (78.3%)
AMR15 (17.2%)16 (18.4%)0 (0%)56 (64.4%)


As compared to the control group, there were more C4d+ & C3d+ EMBs in the pre-AMR (p-values <0.0001 & 0.0013, respectively) & AMR groups (both p-values <0.0001). There were more C4d+ & C3d+ EMBs in the AMR than pre-AMR group. Respectively, C4d & C3d stayed positive in the subsequent AMR EMB in 94.1% & 75% of pre-AMR EMBs. Moreover, C4d & C3d were positive at time of AMR EMB in 46.7% & 60%, respectively.
Conclusions: C4d & C3d positivity are seen more commonly in EMBs with AMR or before AMR. Since only 35.6% & 17.2% of pts diagnosed with AMR demonstrate C4d & C3d positivity, respectively, additional markers of AMR are needed. C4d & C3d staining will be correlated with clinical, hemodynamic, & antibody data.
Category: Cardiovascular

Monday, March 22, 2010 9:30 AM

Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 41, Monday Morning

 

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