Premium
Increased macrophage density of cardiac allograft biopsies is associated with antibody‐mediated rejection and alloantibodies to HLA antigens
Author(s) -
Xu Lauren,
Collins Jennifer,
Drachenberg Cinthia,
KuKuruga Debra,
Burke Allen
Publication year - 2014
Publication title -
clinical transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 76
eISSN - 1399-0012
pISSN - 0902-0063
DOI - 10.1111/ctr.12348
Subject(s) - medicine , macrophage , biopsy , antibody , serology , human leukocyte antigen , antigen , cd68 , pathology , immunology , concordance , immunohistochemistry , biochemistry , chemistry , in vitro
Background Antibody‐mediated rejection ( AMR ) is characterized histologically by intracapillary macrophages. Macrophage density may be an alternative method of determining inflammatory changes in AMR . Methods We identified 118 heart transplant patients with serologic testing for HLA alloantibodies. Macrophage density was graded as 1+ (<45/mm 2 ), 2+ (46–90/mm 2 ), and 3+ (>90/mm 2 ). Maximal macrophage density and complement staining over multiple biopsies were correlated with peak panel reactive antibodies ( PRA ), donor‐specific antibodies ( DSA ), and the clinical diagnosis of AMR . Results The presence of PRA correlated with macrophage score (p = 0.001). Macrophage density correlated with any DSA (p < 0.0001), class I DSA (p < 0.0001), class II DSA (p < 0.0001), and class II DQ (p < 0.0001). Nine patients had clinical AMR . Among patients with AMR , 89% had a biopsy over the period of AMR with ≥3+ macrophage density (89% sensitivity); among patients without AMR , 93% of patients had no biopsy at any time with ≥3+ macrophage density (specificity). There was perfect concordance between the scores of C4d positivity and macrophage density in 61% and only partial concordance in 20%, with complete discordance in 19% in biopsies taken during clinical episodes of AMR . Conclusions Macrophage density in allograft endomyocardial biopsies is frequently elevated during clinical episodes of AMR and correlates well with alloantibodies.