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.
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.
Authors: Benjamin J Kopecky; Christian Frye; Yuriko Terada; Keki R Balsara; Daniel Kreisel; Kory J Lavine Journal: Am J Transplant Date: 2020-01-29 Impact factor: 8.086
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