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Mycophenolate mofetil decreases antibody production after cardiac transplantation

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Abstract

New immunosuppressive drugs are extensively being investigated for their effect on T-cell immunity, with far less being known about their effect on the humoral immune response. In view of the experimental and clinical evidence that humoral immunity contributes to acute and chronic rejection, we investigated post-transplant production of anti-vimentin and anti-HLA antibodies in 86 patients who were part of a worldwide clinical trial for mycophenolate mofetil in cardiac transplantation. The results demonstrate that patients taking MMF instead of azathioprine generated significantly fewer de novo anti-vimentin antibodies.

Section snippets

Methods

The study used sera from 86 patients from three centers who had been part of a double-blind, active controlled trial of 650 patients from 28 centers.12 The patients were randomized to receive MMF (3,000 mg/day) or azathioprine (1.5 to 3 mg/kg per day) in addition to CsA and corticosteroids. Sera were collected before transplant and at 1, 3, 6, 9, 12 and 18 months after transplant. Patients were tested for anti-HLA antibodies and anti-vimentin antibodies using an enzyme-linked immunoassay

Results

The mean 1-year titer of anti-vimentin antibodies in patients taking azathioprine (n = 41) was significantly higher that of MMF patients (n = 45) (p = .01; Table I). There was no difference in mean titer of anti-vimentin antibodies prior to transplantation in these patients (MMF, 69.9 ± 31; Azathioprine, 59.7 ± 21 [mean ± SD]). When results were expressed as number of patients becoming positive for anti-vimentin antibodies (titer > 120) on at least one occasion after transplant, the results

Discussion

Vimentin is an intermediate filament characteristic of fibroblasts, proliferating smooth muscle cells and endothelial cells. It is strongly expressed in blood vessel walls and is involved in vascular remodeling in response to stress-induced injury.15, 16 Our current hypothesis is that antibodies to vimentin reflect an ongoing immune response to damaged parenchymal cells.14 Normally an intracellular protein, it is likely that vimentin is exposed or released from allografted tissues as a result

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    Citation Excerpt :

    Hence AVA are a contributing factor in the pathogenesis of chronic rejection, either indirectly as a marker of tissue damage or directly (mechanisms described below). Studies in heart transplant recipients have also demonstrated different sensitivities to immunosuppressive drugs, hence production of IgM AVA was significantly less in patients receiving myocophenolate mofetil (MMF) than those receiving azathioprine [26]. Production of HLA antibodies were also reduced by MMF.

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