Control of antidonor antibody production with tacrolimus and mycophenolate mofetil in renal allograft recipients with chronic rejection

Details

Serval ID
serval:BIB_0708AF678001
Type
Article: article from journal or magazin.
Collection
Publications
Title
Control of antidonor antibody production with tacrolimus and mycophenolate mofetil in renal allograft recipients with chronic rejection
Journal
Transplantation
Author(s)
Theruvath  T. P., Saidman  S. L., Mauiyyedi  S., Delmonico  F. L., Williams  W. W., Tolkoff-Rubin  N., Collins  A. B., Colvin  R. B., Cosimi  A. B., Pascual  M.
ISSN
0041-1337
Publication state
Published
Issued date
07/2001
Peer-reviewed
Oui
Volume
72
Number
1
Pages
77-83
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Jul 15
Abstract
BACKGROUND: In renal transplantation, chronic rejection is a major cause of late allograft loss. Recent studies indicate that a subset of chronic rejection is associated with anti-HLA donor specific antibodies (DSA) and complement C4d deposition in peritubular capillaries (PTC). Since rescue therapy with tacrolimus and mycophenolate mofetil has been found to limit antidonor B-cell responses in recipients with acute humoral rejection, we sought to determine whether a similar immunosuppressive regimen might be effective in patients with 'chronic humoral rejection'. METHODS: Four renal allograft recipients with 'chronic humoral rejection' were prospectively identified. The diagnosis was based on: (1) progressive rise in serum creatinine over 12 months; (2) typical pathologic features by light microscopy (transplant arteriopathy and glomerulopathy); (3) widespread C4d deposits in PTC by immunofluorescence; (4) detection of 'de novo' DSA at the time of biopsy. Maintenance immunosuppression was CsA, prednisone and azathioprine (n=3) or prednisone and azathioprine (n=1). Rescue therapy with tacrolimus and mycophenolate mofetil was initiated in all patients, 12 hr after cyclosporine and azathioprine discontinuation. RESULTS: At diagnosis, the mean serum creatinine was 3.9 mg/dl (range: 3.3 to 5.4 mg/dl). DSA was an IgG directed against HLA class II (n=3) or class I (n=2), that is one patient had both anti-HLA class I and class II antibodies. Pretreatment antibody titers varied between 1:8 and 1:128. Rescue therapy was associated with a rapid and sustained decrease in antibody titers. In two patients, DSA became undetectable after 9 months and a repeat biopsy performed after 12 months revealed a decrease in C4d deposition in PTC. CONCLUSION: These results suggest that a decrease in DSA production can be induced in renal allograft recipients with 'chronic humoral rejection' by using an immunosuppressive regimen that combines tacrolimus and mycophenolate mofetil. Limitation of antidonor antibody synthesis may be important for the treatment or the prevention of chronic rejection in organ transplantation.
Keywords
Adult Antibodies/*immunology Antibody Formation/drug effects Antibody Specificity B-Lymphocytes/immunology Chronic Disease Drug Therapy, Combination Graft Rejection/*drug therapy/*immunology Humans Immunosuppressive Agents/*therapeutic use Kidney Transplantation/*immunology Male Middle Aged Mycophenolic Acid/analogs & derivatives/*therapeutic use Prospective Studies Tacrolimus/*therapeutic use *Tissue Donors Transplantation, Homologous
Pubmed
Web of science
Create date
29/01/2008 13:52
Last modification date
20/08/2019 12:29
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