Immune responsiveness in renal transplant recipients: Mycophenolic acid severely depresses humoral immunity in vivo

Rentenaar, Rob J.; Diepen, F. N. J. Van; Meijer, R. T.; Surachno, S.; Wilmink, J. M.; Schellekens, P. T. A.; Pals, Steven T.; Lier, R. A. W. Van; Berge, Ineke J. M. ten

doi:10.1046/j.1523-1755.2002.00425.x

Cited by 73 publications

(84 citation statements)

References 25 publications

(1 reference statement)

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“…This finding confirms and extends the data from several small series, published in recent years, showing a suppressed humoral immune response in MMF-treated patients (15)(16)(17)27). Nonetheless, in the present study patients on MMF therapy had SP rates after vaccination that ranged from 74 to 88%.…”

Section: Scharpé Et Alsupporting

confidence: 93%

Influenza Vaccination Is Efficacious and Safe in Renal Transplant Recipients

Scharpé¹,

Evenepoel²,

Maes³

et al. 2008

American Journal of Transplantation

149

131

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Whether influenza vaccination in solid-organ transplant recipients is efficacious remains a controversial issue. Furthermore, theoretical concerns have been raised regarding the safety of vaccination as it might trigger rejection of the allograft. The present prospective trial is aimed at investigating the antibody response and safety of influenza vaccination in renal transplant recipients (RTR).A total of 165 RTR and 41 healthy volunteers were vaccinated with a standard trivalent inactivated influenza vaccine. Hemagglutination-inhibiting (HI) antibodies were quantified before and 1 month after vaccination. Seroprotection (SP) and seroresponse (SR) were defined as a titer ≥40 and a 4-fold rise in HI titer, respectively. Similar SR rates were observed in both groups. Postvaccination SP rates in RTR amounted to 92.7%, 78.7% and 82.9% for A/H1N1, A/H3N2 and B, respectively. High baseline SP rates, most probably reflecting frequent preimmunizations, explain partly the high postvaccination SP rates. SR rate was independently and inversely associated with baseline SP rate. Mycophenolate mofetil (MMF) usage was associated with a 2.6-5-fold lower SR. Nonetheless, these patients showed good postvaccination SP rates. A booster dose did not enhance SP or SR rates. Influenza vaccination neither affected allograft function nor caused rejection episodes. In conclusion, influenza vaccination is efficacious and safe in renal transplantation.

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Section: Scharpé Et Alsupporting

confidence: 93%

Influenza Vaccination Is Efficacious and Safe in Renal Transplant Recipients

Scharpé¹,

Evenepoel²,

Maes³

et al. 2008

American Journal of Transplantation

149

131

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“…In recent studies, MMF has been shown to be capable of depressing humoral immunity in renal allograft recipients (20). In the present case, the substitution of MMF for azathioprine was associated with a significant decrease in T lymphocyte-reactive anti-HLA-A11 DSA by FC, but not its complete disappearance.…”

Section: Discussionsupporting

confidence: 44%

Ultra‐Late Antibody‐Mediated Rejection 30 Years After a Living‐Related Renal Allograft

Weinstein¹,

Braun²,

Cook³

et al. 2005

American Journal of Transplantation

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Antibody-mediated renal allograft rejection has become increasingly recognized and more clearly defined through the use of flow cytometry cross-matching and the deposition of C4d in renal allograft biopsies. All of the cases reported thus far have developed an antibody within 10 years of transplantation, and many lacked HLA and/or donor specificity.The present patient developed an anti-HLA donorspecific antibody between the 22nd and 30th year after a living-related renal transplant. At the 30th year posttransplantation, she experienced a rise in the serum creatinine from 0.7 to 1.9 mg/dL associated with transplant biopsy C4d deposition in peritubular capillaries and glomeruli. After the replacement of azathioprine with mycophenolate mofetil, and six apheresis treatments followed by two infusions of IVIG, the renal function stabilized at 1.9 mg/dL, 33 years after transplantation. Antibody-mediated rejection must be considered as a possible cause or renal allograft dysfunction at all time periods after transplantation.

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“…These data suggest that the presence of HLA antibodies, DS but also NDS, is associated with transplant failure and that their screening is an important tool for the treatment of patients who receive a kidney transplant, as they could help in discriminating between chronic rejection and nonimmune allograft dysfunction. This discrimination could have therapeutic implications and could lead to specific treatment aimed at either inhibiting their production, such as MMF (16) or the CD20 mAb (17), or neutralizing their action, with plasma exchange and/or intravenous Ig (17)(18)(19)(20), that are used with success in acute vascular rejection. …”

Section: Discussionmentioning

confidence: 99%

Frequency and Clinical Implications of Development of Donor-Specific and Non–Donor-Specific HLA Antibodies after Kidney Transplantation

Hourmant¹,

Cesbron‐Gautier²,

Terasaki

et al. 2005

Journal of the American Society of Nephrology

271

176

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The involvement of immunologic and nonimmunologic events in long-term kidney allograft failure is difficult to assess. The development of HLA antibodies after transplantation is the witness of ongoing reactivity against the transplant, and several studies have suggested that the presence of HLA antibodies correlates with poor graft survival. However, they have not discriminated between donor-specific (DS) and non-specific (NDS) antibodies. A total of 1229 recipients of a kidney graft, transplanted between 1972 and 2002, who had over a 5-yr period a prospective annual screening for HLA antibodies with a combination of ELISA, complement-dependent cytotoxicity, and flow cytometry tests were investigated; in 543 of them, the screening was complete from transplantation to the fifth year postgrafting. Correlations were established between the presence and the specificity of the antibodies and clinical parameters. A total of 5.5% of the patients had DS, 11.3% had NDS, and 83% had no HLA antibodies after transplantation. NDS antibodies appeared earlier (1 to 5 yr posttransplantation) than DS antibodies (5 to 10 yr). In multivariate analysis, HLA-DR matching, pretransplantation immunization, and acute rejection were significantly associated with the development of both DS and NDS antibodies and also of DS versus NDS antibodies. The presence of either DS or NDS antibodies significantly correlated with lower graft survival, poor transplant function, and proteinuria. Screening of HLA antibodies posttransplantation could be a good tool for the follow-up of patients who receive a kidney transplant and allow immunosuppression to be tailored.

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Immune responsiveness in renal transplant recipients: Mycophenolic acid severely depresses humoral immunity in vivo

Cited by 73 publications

References 25 publications

Influenza Vaccination Is Efficacious and Safe in Renal Transplant Recipients

Influenza Vaccination Is Efficacious and Safe in Renal Transplant Recipients

Ultra‐Late Antibody‐Mediated Rejection 30 Years After a Living‐Related Renal Allograft

Frequency and Clinical Implications of Development of Donor-Specific and Non–Donor-Specific HLA Antibodies after Kidney Transplantation

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