CORRELATION OF ANTI–VIMENTIN ANTIBODIES WITH ACUTE AND CHRONIC REJECTION FOLLOWING CARDIAC TRANSPLANTATION

6.3
TITLE: CORRELATION OF ANTI–VIMENTIN ANTIBODIES WITH ACUTE AND CHRONIC REJECTION FOLLOWING CARDIAC TRANSPLANTATION

Anna J Danskine,¹ John D. Smith,¹ Rachel E. Stanford,¹ Helen Newell,¹ Marlene L. Rose.¹

¹NHLI, Imperial College School of Science, Technology & Medicine, Harefield Hospital, United Kingdom

Vimentin is a protein found in fibroblasts and smooth muscle cells within blood vessels. We have previously shown that de–novo production of anti–vimentin antibodies (Abs) is associated with development of transplant associated coronary artery disease (TxCAD) after cardiac transplantation. This prospective study aimed to investigate whether pre–transplant levels of anti–vimentin Abs correlate with acute or chronic rejection following cardiac transplantation and the effect of post transplant production of antibodies.

Vimentin Abs were detected using an in house ELISA method. Patients sera were tested prior to and at 1, 3, 6, 12 months and annually after transplantation whenever possible. Rejection episodes were defined as biopsy proven (grade 1A, 1B or 3A) treated episodes.

IgM anti–vimentin Abs were detected in 42 of 167 patients prior to transplantation; No correlation was seen with presenting disease. Pre–transplant Abs were associated with acute rejection in the post–operative period. Thus Ab positive patients experienced 1.74 rejection episodes (RE) +/– 0.22 (SE) within 6 months compared to 1.31 +/− 0.10 for Ab negative patients (p = 0.052). Similarly at 12 months, positive patients experienced significantly more RE ( 2.29+/– 0.30) than Ab negative patients (1.65+/– 0.12, p = 0.022).

There was no correlation between Ab production post–operatively and the number of rejection episodes. 74 patients had survived for at least 2 years following transplant and undergone angiography to determine the degree of TxCAD. 10 of 11 patients who developed TxCAD within two years of transplant (90.9%) produced IgM anti–vimentin Abs compared to 27 of 63 (42.8%) recipients who had not developed TxCAD 2 or more years after transplantation (p = 0.02). In addition the mean titre of anti–vimentin Abs was 267.9 +/– 75.8 for the TxCAD patients compared to 166.9+/– 16.9 for the patients without TxCAD (p = 0.051).

In conclusion, these results confirm that the presence of anti–vimentin Abs is associated with a vigorous immune response against the graft. Whether the antibodies themselves directly damage the graft is currently under investigation.