PATHOGENESIS OF QUILTY LESION IN CARDIAC ALLOGRAFTS - RELATIONSHIP TOREDUCED ENDOCARDIAL CYCLOSPORINE-A

Background: Endocardial lymphocytic infiltrates, known as Quilty effec t, are a common finding of uncertain pathogenesis in cardiac allograft s. 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 Quilt y effect may be related to a relative absence of cyclosporine A in thi s region. Methods: We used an indirect immunofluorescence staining met hod with rabbit polyclonal anti-cyclosporine A antibodies to detect cy closporine A in fresh frozen sections of 27 cardiac allograft endomyoc ardial biopsies. Staining was graded 0 to + 3. Negative controls were from untreated transplant candidates and from biopsies with the primar y antibody omitted. Results: On comparison of endocardial and myocardi al fluorescence in biopsy specimens from patients treated with cyclosp orine A, there was less endocardial (0.7 +/- 1.1, p < 0.0001) than myo cardial (2.2 +/- 0.5) staining. However, in biopsy specimens with Quil ty effect (n = 12), this difference was significantly greater (endocar dial = 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 v ersus myocardial = 2.1 +/- 0.6; p = 0.7). Endocardial thickness as mea sured by ocular micrometry was significantly greater in regions with ( 32 +/- 19 mu m) than without (7 +/- 4 mu m) Quilty effect, with involv ed regions showing increased connective tissue (p < 0.0001). In patien ts with and without Quilty effect, no differences in donor or recipien t demographics, prevalence of diabetes, or plasma cyclosporine A level s were found. Conclusions: Although it has been postulated that Quilty effect is due to the presence of cyclosporine A in cardiac tissue (to xic effect or immunologic reaction), these data suggest that Quilty ef fect is related to reduced endocardial presence of cyclosporine A, lea ding to localized, contained, and usually not clinically significant e ndocardial rejection.