Acute vascular humoral rejection in a sensitized cardiac graft recipient: diagnostic value of C4d immunofluorescence

A 37-year-old female patient had a cardiac transplantation for dilated cardiomyopathy. She was sensitized by two pregnancies showing anti-human leukocyte antigen I and II antibodies. The pretransplantation crossmatch was negative, but she developed acute humoral rejection characterized by vascular C4d deposits, arteriolitis, and intravascular leukocyte accumulation and adhesion in venules. Although C4d deposits disappeared in 4 weeks, she had persistent endothelial cell activation (endothelial expression of ELAM-1, VCAM-1, or human leukocyte antigen class II) throughout the 6 months of follow-up. Although she received intensive immunosuppression, she presented three episodes of acute cellular rejection during that period of time. This case shows that C4d deposits represent a sensitive marker of acute humoral rejection in cardiac transplantation. Therefore, C4d immunofluorescence should be more frequently assessed in endomyocardial biopsies.