title: Inflammatory cell burden and phenotype in endomyocardial biopsies with antibody-mediated rejection (AMR): a multicenter pilot study from the AECVP.
abstract: This multicenter case-controlled pilot study evaluated myocardial inflammatory burden (IB) and phenotype in endomyocardial biopsies (EMBs) with and without pathologic antibody-mediated rejection (pAMR). Sixty-five EMBs from five European heart transplant centers were centrally reviewed as positive (grade 2, n = 28), suspicious (grade 1, n = 7) or negative (n = 30) for pAMR. Absolute counts of total, intravascular (IV) and extravascular (EV) immunophenotyped mononuclear cells were correlated with pAMR grade, capillary C4d deposition, donor specific antibody (DSA) status and acute cellular rejection (ACR). In pAMR+ biopsies, equivalent number of IV CD3+ T lymphocytes (23 ± 4/0.225 mm(2) ) and CD68+ macrophages (21 ± 4/0.225 mm(2) ) were seen. IB and cell phenotype correlated with pAMR grade, C4d positivity and DSA positivity (p < 0.0001). High numbers of IV T lymphocytes were associated with low grade ACR (p = 0.002). In late-occurring AMR EV plasma cells occurring in 34% of pAMR+ EMBs were associated with higher IB. The IB in AMR correlated with pAMR+, C4d positivity and DSA positivity. In pAMR+ equivalent numbers of IV T lymphocytes and macrophages were found. The presence of plasma cells was associated with a higher IB and occurrence of pAMR late after transplantation.
authors.affiliation: Department of Cardiac, Thoracic and Vascular Sciences, University of Padua, Padua, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Fedrigo
authors.forename: O
authors.initials: O
authors.lastname: Leone
authors.forename: M M
authors.initials: MM
authors.lastname: Burke
authors.forename: A
authors.initials: A
authors.lastname: Rice
authors.forename: C
authors.initials: C
authors.lastname: Toquet
authors.forename: D
authors.initials: D
authors.lastname: Vernerey
authors.forename: A-C
authors.initials: AC
authors.lastname: Frigo
authors.forename: R
authors.initials: R
authors.lastname: Guillemain
authors.forename: S
authors.initials: S
authors.lastname: Pattier
authors.forename: J
authors.initials: J
authors.lastname: Smith
authors.forename: A
authors.initials: A
authors.lastname: Lota
authors.forename: L
authors.initials: L
authors.lastname: Potena
authors.forename: A
authors.initials: A
authors.lastname: Bontadini
authors.forename: C
authors.initials: C
authors.lastname: Ceccarelli
authors.forename: F
authors.initials: F
authors.lastname: Poli
authors.forename: G
authors.initials: G
authors.lastname: Feltrin
authors.forename: G
authors.initials: G
authors.lastname: Gerosa
authors.forename: E
authors.initials: E
authors.lastname: Manzan
authors.forename: G
authors.initials: G
authors.lastname: Thiene
authors.forename: P
authors.initials: P
authors.lastname: Bruneval
authors.forename: A
authors.initials: A
authors.lastname: Angelini
authors.forename: J-P
authors.initials: JP
authors.lastname: Duong Van Huyen
mesh_terms: D000328:Adult; D000906:Antibodies / Q000276:immunology*; D001706:Biopsy; D002196:Capillaries / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D015935:Complement C4b / Q000378:metabolism; D005060:Europe; D005260:Female; D006084:Graft Rejection / Q000453:epidemiology / Q000276:immunology* / Q000473:pathology*; D016027:Heart Transplantation; D006801:Humans; D015994:Incidence; D007249:Inflammation / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009205:Myocarditis / Q000473:pathology*; D010446:Peptide Fragments / Q000378:metabolism; D010641:Phenotype; D010865:Pilot Projects; D012189:Retrospective Studies; D014019:Tissue Donors
chemical_list: D000906:Antibodies; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d
keywords: Biopsy; classification systems: ISHLT classification; clinical research; heart transplantation: cardiology; histopathology; macrophage; monocyte biology: activation; pathology; practice; rejection: antibody-mediated (ABMR)