Journal article
Application of operational tolerance signatures are limited by variability and type of immunosuppression in renal transplant recipients: A cross-sectional study.
- Abstract:
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Background
Renal transplant recipients (RTR) frequently develop complications relating to chronic immunosuppression. Identifying RTR who could safely reduce immunosuppression is therefore highly desirable. We hypothesized that “signatures” described in RTR who have stopped immunosuppression but maintained stable graft function (“operational tolerance”) may enable identification of immunosuppressed RTR who are candidates for immunosuppression minimization. However, the effect of immunosuppression itself on these signatures and circulating B-cell populations is currently unknown.
Methods
We undertook a cross-sectional study of 117 RTR to assess the effect of immunosuppression upon circulating B cell populations, humoral alloresponse and 2 previously published “signatures” of operational tolerance.
Results
Immunosuppression associated with alterations in both published “signatures.” Azathioprine associated with a decrease in transitional and naive B-cell numbers and calcineurin inhibition associated with an increase in the number of circulating plasmablasts. However, only azathioprine use associated with the presence of donor-specific anti-HLA IgG antibodies. Calcineurin inhibition associated with an increase in total serum IgM but not IgG. Data were corrected for age, time since last transplant, and other immunosuppression.
Conclusions
Current signatures of operational tolerance may be significantly affected by immunosuppressive regimen, which may hinder use in their current form in clinical practice. Calcineurin inhibition may prevent the development of long-lasting humoral alloresponses, whereas azathioprine therapy may be associated with donor specific antibody development.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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- Files:
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(Preview, Version of record, pdf, 514.0KB, Terms of use)
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- Publisher copy:
- 10.1097/txd.0000000000000638
Authors
- Publisher:
- Lippincott, Williams and Wilkins
- Journal:
- Transplantation Direct More from this journal
- Volume:
- 3
- Issue:
- 1
- Pages:
- e125
- Publication date:
- 2016-12-01
- Acceptance date:
- 2016-10-28
- DOI:
- EISSN:
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2373-8731
- Pmid:
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28349125
- Language:
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English
- Keywords:
- Pubs id:
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pubs:687888
- UUID:
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uuid:5afd381f-1d5a-44ee-a4a6-280b11e6b14b
- Local pid:
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pubs:687888
- Source identifiers:
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687888
- Deposit date:
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2018-03-22
Terms of use
- Copyright holder:
- Bottomley et al
- Copyright date:
- 2016
- Notes:
- Copyright © 2016 The Authors. Transplantation Direct. Published byWolters Kluwer Health, Inc. This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
- Licence:
- CC Attribution (CC BY)
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