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      Antibody Response to Influenza Immunization in Kidney Transplant Recipients Receiving either Azathioprine or Mycophenolate: A Controlled Trial

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          Abstract

          Aims: We aimed to assess humoral immune response to the influenza vaccine in adult kidney transplant recipients (KTRs) subjected to two immunosuppressive regimens containing either mycophenolate mofetil (MMF) or azathioprine (Aza). Methods: 40 eligible KTRs (24 treated with Aza [KTRs-Aza] and 16 treated with MMF [KTRs-MMF]) and 40 matched healthy controls (HCs) were administered the trivalent 2006–2007 anti-influenza vaccine. Antibody (Ab) titers were measured before (pre-vacc) and 1 month after (post-vacc) vaccination. The proportion of protective Ab titers (i.e. ≧1:40), the serological response (i.e. ≧4-fold rise in titers) rates, and the magnitudes of change in titers were evaluated. Results: KTRs and HCs were similar in serologic responses, magnitudes of change in Ab titers, and proportions of acquired protective titers against all antigens. Whereas KTRs-MMF and KTRs-Aza were identical in magnitude of rise in titers as well as in serologic responses, KTRs-MMF did poorer in developing post-vacc-protective titers against A/H1N1 (p < 0.05). The function of the transplanted kidney has not deteriorated after vaccination. Conclusions: Anti-influenza vaccination was safe in KTRs and evoked Ab responses comparable to those of HCs. KTRs-MMF and KTRs-Aza responded almost equally to the vaccine. Annual anti-influenza vaccination can be recommended to all stable KTRs.

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          Most cited references19

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          Excess mortality due to pneumonia or influenza during influenza seasons among persons with acquired immunodeficiency syndrome.

          Anecdotal reports suggest that influenza-related morbidity may be high among persons with acquired immunodeficiency syndrome (AIDS), but little information is available concerning the population-level impact of influenza on mortality in persons with AIDS. Using the Multiple Cause-of-Death data files, which contain information on all deaths occurring in the United States each year, we calculated the numbers of excess deaths and rates of excess death due to pneumonia or influenza among persons with AIDS aged 13 years and older during the influenza seasons 1991-1992 through 1993-1994. For comparison, numbers of excess deaths and excess death rates were also calculated for several other groups including the general US population aged 13 years and older and the general US population aged 65 years and older. During the 1991-1992, 1992-1993, and 1993-1994 influenza seasons, there were 261, 254, and 191 excess deaths due to pneumonia or influenza in persons with AIDS and excess death rates of 19.74, 15.38, and 10.17 deaths per 10 000 persons, respectively, compared with a summer baseline period. For the same seasons, we observed excess death rates of 1.40, 1.62, and 1.48 for the general US population aged 13 years and older and 8.10, 9.28, and 8.54 for the general US population aged 65 years and older. Thus, persons with AIDS had excess death rates substantially higher than the general US population and similar to, if not somewhat higher than, the general US population aged 65 years and older, a group that is already targeted for annual vaccination. The findings were similar when we compared the preinfluenza season with the influenza season. Persons with AIDS have significant excess mortality due to pneumonia or influenza during influenza seasons and should be considered a high-risk group that is targeted for the prevention of influenza.
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            Mechanisms of action of mycophenolate mofetil

            AC Allison (2005)
            Mycophenolate mofetil (MMF, CellCept®) is a prodrug of mycophenolic acid (MPA), an inhibitor of inosine-5′-monophosphate dehydrogenase. MPA depletes guanosine nucleotides preferentially in T and B lymphocytes and inhibits their proliferation, thereby suppressing cell-mediated immune responses and antibody formation. MPA also inhibits the glycosylation and expression of adhesion molecules, and the recruitment of lymphocytes and monocytes into sites of inflammation. MPA depletes tetrahydrobiopterin and decreases the production of nitric oxide by inducible NO synthase without affecting the activity of constitutive NO synthases. Activated macrophages produce NO and superoxide, which combine to generate tissue-damaging peroxynitrite. By these two mechanisms MMF exerts anti-inflammatory activity. Unlike calcineurin inhibitors, MMF is not nephrotoxic and does not induce the production of TGF΢, which is fibrogenic. MMF does not increase blood pressure, cholesterol levels or triglyceride levels in recipients. MMF reduces acute and chronic rejection in allograft recipients and is efficacious in some nephropathies. Evidence is accumulating that MMF may have clinical utility in some autoimmune disorders.
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              Suppression of the humoral immune response by mycophenolate mofetil.

              No conventional immunosuppressive agent preferentially inhibits antibody production. Studies in experimental animals and in human cells in vitro suggested mycophenolate mofetil (MMF) might have such an effect. If this was the case in vivo it could have significant implications in terms of both MMF toxicity and the rational design of immunotherapeutic regimens.
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                Author and article information

                Journal
                AJN
                Am J Nephrol
                10.1159/issn.0250-8095
                American Journal of Nephrology
                S. Karger AG
                0250-8095
                1421-9670
                2008
                June 2008
                06 March 2008
                : 28
                : 4
                : 654-660
                Affiliations
                aInfectious Diseases and Tropical Medicine Research Center, Shahid Beheshti University (M.C.), Tehran, bClinical Laboratory Center, Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, cClinical Research & Development Center, Nephrology Department, Shahid Modarres Medical Center, Shahid Beheshti University (M.C.), and dDepartment of Virology, School of Public Health, Tehran Medical University, Tehran, Iran
                Article
                119742 Am J Nephrol 2008;28:654–660
                10.1159/000119742
                18322360
                96787deb-a187-4143-bb5a-b3ad52fd872a
                © 2008 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 26 August 2007
                : 17 January 2008
                Page count
                Figures: 2, Tables: 3, References: 33, Pages: 7
                Categories
                Original Report: Laboratory Investigation

                Cardiovascular Medicine,Nephrology
                Azathioprine,Mycophenolate mofetil,Influenza,Vaccination,Immunization,Kidney transplant recipient,Antibody response

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