title: The presence of anti-HLA donor-specific antibodies in lung allograft recipients does not correlate with C4d immunofluorescence in transbronchial biopsy specimens.
abstract: BACKGROUND
  C4d immunofluorescence (IF) is a surrogate for development of donor-specific antibodies (DSAs) against human leukocyte antigen (HLA) class I and II antigens in kidney and heart biopsy specimens for monitoring of antibody-mediated (humoral) allograft rejection (AMR). Use of C4d IF in monitoring of lung allografts has shown conflicting results.
  
  
  OBJECTIVE
  To determine if C4d IF can be used as a reliable marker for AMR and if it correlates with the presence of DSAs and histologic findings on biopsy.
  
  
  METHODS
  All transbronchial biopsies in lung allograft recipients, performed at our institution in a 3-year period, were reviewed. A cohort of 92 patients with 110 corresponding biopsies met the inclusion criteria of (1) having a resulted DSA within 2 weeks of biopsy and (2) having C4d immunofluorescence studies performed and confirmed.
  
  
  RESULTS
  Twenty-nine patients (31.5%) were positive for DSAs and 63 patients (68.5%) did not develop DSAs. Positive C4d capillary IF was seen in 18 of 110 total biopsy specimens (16.4%). Eight of these biopsy samples were from patients positive for DSAs and 10 were from patients negative for DSAs. The correlation coefficient between the presence of DSAs and C4d IF was 0.1628 (P = .09).
  
  
  CONCLUSIONS
  A significant proportion of DSA-positive patients had negative C4d IF results and frequently have no histologic changes on biopsy specimens. DSA-negative patients can be positive for C4d and may show the same histologic changes as reported for DSA-positive patients. Diagnosis of AMR in lung may require a collaborative approach combining clinical data, DSA status, and histology.
authors.affiliation: From the Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas (Drs Roberts, Barrios, Cagle, Ge, Takei, Haque, Burns, Land, Dilioglou, and Bernard); and the Department of Pathology, Weill Cornell Medical College of Cornell University, Houston, Texas (Drs Barrios, Cagle, Ge, and Takei).
authors.forename: Jordan A
authors.initials: JA
authors.lastname: Roberts
authors.forename: Roberto
authors.initials: R
authors.lastname: Barrios
authors.forename: Philip T
authors.initials: PT
authors.lastname: Cagle
authors.forename: Yimin
authors.initials: Y
authors.lastname: Ge
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Takei
authors.forename: Abida K
authors.initials: AK
authors.lastname: Haque
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Burns
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Land
authors.forename: Smaroula
authors.initials: S
authors.lastname: Dilioglou
authors.forename: David W
authors.initials: DW
authors.lastname: Bernard
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D001980:Bronchi / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015331:Cohort Studies; D015935:Complement C4b / Q000378:metabolism*; D005260:Female; D019085:Fluorescent Antibody Technique, Direct; D005500:Follow-Up Studies; D006680:HLA Antigens / Q000378:metabolism*; D016519:Hospitals, Religious; D006789:Host vs Graft Reaction; D006801:Humans; D056724:Immunity, Humoral; D007518:Isoantibodies / Q000378:metabolism*; D016040:Lung Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000378:metabolism*; D013781:Texas; D014184:Transplantation, Homologous
chemical_list: D015415:Biomarkers; D006680:HLA Antigens; D007518:Isoantibodies; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d