Serial monitoring of humoral antibody-mediated rejection of cardiac allografts by C4d staining of interstitial capillaries.

C4d "staining" of interstitial capillaries of endomyocardial biopsies serves as an indicator of a humoral component of cardiac allograft rejection. In the present study, two cardiac allograft recipients were monitored serially for both cellular and humoral rejection. Cellular rejection, evaluated by light microscopy, and humoral rejection, judged by C4d immunofluorescent "staining", were treated with appropriate immunosuppressants. Weekly serial biopsies of the first patient revealed maximal humoral rejection (3+) after 1 week but diminished to 2+ thereafter. Cellular rejection was graded as 3A after 3 weeks but declined steadily to negligible cellular rejection through week 15. Whereas, cellular rejection peaked at 14-21 days, humoral rejection was greatest in the early post-transplant period. Biopsies of the second patient for 12 weeks revealed grade 1A to 1B moderate cellular rejection. Humoral rejection peaked at 3+ "staining" for C4d after 1 week transplant, and then wavered between 2+ (moderate "staining") and 1+ (weak "staining"). Results revealed the significance not only of traditional light microscopy in evaluating the severity of cellular rejection in endomyocardial biopsies of cardiac allotransplants, but also the value of C4d immunofluorescent "staining" of interstitial capillaries as an indicator of humoral rejection episodes, which may require modified therapy.