title: Pathogenesis of Quilty lesion in cardiac allografts: relationship to reduced endocardial cyclosporine A.
abstract: BACKGROUND
  Endocardial lymphocytic infiltrates, known as Quilty effect, are a common finding of uncertain pathogenesis in cardiac allografts. Quilty effect was not observed before the use of cyclosporine A for immunosuppression and is not generally regarded as a manifestation of rejection. We hypothesized that the endocardial localization of Quilty effect may be related to a relative absence of cyclosporine A in this region.
  
  
  METHODS
  We used an indirect immunofluorescence staining method with rabbit polyclonal anti-cyclosporine A antibodies to detect cyclosporine A in fresh frozen sections of 27 cardiac allograft endomyocardial biopsies. Staining was graded 0 to +3. Negative controls were from untreated transplant candidates and from biopsies with the primary antibody omitted.
  
  
  RESULTS
  On comparison of endocardial and myocardial fluorescence in biopsy specimens from patients treated with cyclosporine A, there was less endocardial (0.7 +/- 1.1, p < 0.0001) than myocardial (2.2 +/- 0.5) staining. However, in biopsy specimens with Quilty effect (n = 12), this difference was significantly greater (endocardial = 0.2 +/- 0.6 versus myocardial = 2.3 +/- 0.5; p = 0.005) than in specimens without Quilty effect (n = 10) (endocardial = 1.4 +/- 1.2 versus myocardial = 2.1 +/- 0.6; p = 0.7). Endocardial thickness as measured by ocular micrometry was significantly greater in regions with (32 +/- 19 microns) than without (7 +/- 4 microns) Quilty effect, with involved regions showing increased connective tissue (p < 0.0001). In patients with and without Quilty effect, no differences in donor or recipient demographics, prevalence of diabetes, or plasma cyclosporine A levels were found.
  
  
  CONCLUSIONS
  Although it has been postulated that Quilty effect is due to the presence of cyclosporine A in cardiac tissue (toxic effect or immunologic reaction), these data suggest that Quilty effect is related to reduced endocardial presence of cyclosporine A, leading to localized, contained, and usually not clinically significant endocardial rejection.
authors.affiliation: Division of Cardiology, Cedars-Sinai Medical Center, Los Angeles, Calif 90048, USA.
authors.forename: D
authors.initials: D
authors.lastname: Freimark
authors.forename: L S
authors.initials: LS
authors.lastname: Czer
authors.forename: I
authors.initials: I
authors.lastname: Aleksic
authors.forename: X M
authors.initials: XM
authors.lastname: Ruan
authors.forename: D
authors.initials: D
authors.lastname: Admon
authors.forename: C
authors.initials: C
authors.lastname: Blanche
authors.forename: A
authors.initials: A
authors.lastname: Trento
authors.forename: M C
authors.initials: MC
authors.lastname: Fishbein
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D003238:Connective Tissue / Q000473:pathology; D016572:Cyclosporine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004699:Endocardium / Q000473:pathology*; D019084:Fluorescent Antibody Technique, Indirect; D006084:Graft Rejection / Q000473:pathology*; D016027:Heart Transplantation / Q000473:pathology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008218:Lymphocytosis / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology*
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine