title: Humoral heart rejection (severe allograft dysfunction with no signs of cellular rejection or ischemia): incidence, management, and the value of C4d for diagnosis.
abstract: Severe allograft dysfunction after heart transplant (HT), without ischemia or evidence of cellular rejection upon endomyocardial biopsy (EMB), is a rare but potentially fatal condition that suggests humoral rejection (HR). Its incidence, and the methods of choice for its diagnosis and management, remain uncertain. We retrospectively studied 445 HT patients (April 1991-December 2003) to determine incidence of HR diagnosed by clinical and conventional histopathological criteria. We used immunofluorescence (IF) techniques to test archived frozen EMB issue for IgM, IgG, C1q, C3, fibrin and C4d. Twelve patients (2.7%) fulfilled the criteria for HR after a mean time post-HT of 21.3 +/- 24.7 months (range: 2-72 months). Patients were treated with high doses of steroids and plasmapheresis, with successful recovery in 11 cases. IF studies using classical markers were mainly negative for the six patients with enough EMB tissue for testing. All six patients showed positivity for C4d during the HR episode but not before or after. Humoral rejection was observed in less than 3% of HT patients. Plasmapheresis treatment was highly effective. Classical IF tests were not useful for diagnosis, but C4d appears to be useful both for confirmation of diagnosis and for monitoring response to treatment.
authors.affiliation: Unidad de Trasplante Cardiaco, Hospitalario Universitario Juan Canalejo, La Coruna, Spain. mcrelei@canalejo.org
authors.forename: Maria G
authors.initials: MG
authors.lastname: Crespo-Leiro
authors.forename: Alberto
authors.initials: A
authors.lastname: Veiga-Barreiro
authors.forename: Nieves
authors.initials: N
authors.lastname: Doménech
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Paniagua
authors.forename: Pablo
authors.initials: P
authors.lastname: Piñón
authors.forename: Margarita
authors.initials: M
authors.lastname: González-Cuesta
authors.forename: Eduardo
authors.initials: E
authors.lastname: Vázquez-Martul
authors.forename: Consuelo
authors.initials: C
authors.lastname: Ramirez
authors.forename: Jose J
authors.initials: JJ
authors.lastname: Cuenca
authors.forename: Alfonso
authors.initials: A
authors.lastname: Castro-Beiras
mesh_terms: D000328:Adult; D000368:Aged; D000917:Antibody Formation / Q000502:physiology*; D015703:Antigens, CD / Q000096:biosynthesis; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis; D015415:Biomarkers; D001706:Biopsy; D015922:Complement C1q / Q000096:biosynthesis; D003176:Complement C3 / Q000096:biosynthesis; D015935:Complement C4b / Q000096:biosynthesis*; D005260:Female; D005337:Fibrin / Q000096:biosynthesis; D005500:Follow-Up Studies; D006084:Graft Rejection; D006085:Graft Survival; D016027:Heart Transplantation / Q000379:methods*; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D007511:Ischemia; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology*; D010446:Peptide Fragments / Q000096:biosynthesis*; D010956:Plasmapheresis; D012189:Retrospective Studies; D013256:Steroids / Q000627:therapeutic use; D013997:Time Factors; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D015922:Complement C1q; D003176:Complement C3; D015935:Complement C4b; D005337:Fibrin; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D010446:Peptide Fragments; D013256:Steroids; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C032261:complement C4d