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Journal article

Application of operational tolerance signatures are limited by variability and type of immunosuppression in renal transplant recipients: A cross-sectional study.

Abstract:

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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Publisher copy:
10.1097/txd.0000000000000638

Authors


More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Surgical Sciences
Role:
Author
ORCID:
0000-0001-5793-4777
More by this author
Role:
Author
ORCID:
0000-0003-2342-4861
More by this author
Institution:
University of Oxford
Division:
Medical Sciences Division
Department:
Surgical Sciences
Role:
Author
More by this author
Institution:
University of Oxford
Division:
Medical Sciences Division
Role:
Author
More by this author
Institution:
University of Oxford
Division:
Medical Sciences Division
Department:
Surgical Sciences
Oxford college:
Green Templeton College
Role:
Author



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:
2373-8731
Pmid:
28349125


Language:
English
Keywords:
Pubs id:
pubs:687888
UUID:
uuid:5afd381f-1d5a-44ee-a4a6-280b11e6b14b
Local pid:
pubs:687888
Source identifiers:
687888
Deposit date:
2018-03-22

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