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Presence and levels of non-complement fixing IgG4 subclass associates with early graft rejection and decreased allograft survival times in antibody incompatible transplantation
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Khovanova, N. A., Lowe, David Philip, Daga, Sunil, Shaikhina, Torgyn, Krishnan, Nithya, Zehnder, Daniel, Briggs, David and Higgins, Rob (2014) Presence and levels of non-complement fixing IgG4 subclass associates with early graft rejection and decreased allograft survival times in antibody incompatible transplantation. In: Third International Transplantation conference : How much risk can you take and what to do if it all goes pear shaped., University of Warwick, UK, 31 Oct -1 Nov 2014 (Unpublished)
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Official URL: http://www.btscongress.com/posters-p055-071.html
Abstract
It is known that donor specific antibodies (DSA) represent a risk factor for early transplant rejection and influence allograft survival times. The aim of this research was to investigate the role of all DSA IgG subclasses (1-4) in the immune response in order to identify any potentially damaging antibodies and their influence on short and long postoperative outcome.
77 transplanted samples were available for short-term outcome analysis comprising 43 cases experiencing rejection (R) episodes within the first 30 days after transplantation and 34 cases of non-rejectors (NR). IgG (1-4) DSA levels were determined for all pre-transplant, peak and 30th day post-transplant samples. We also divided the samples into 2 groups according to long-term outcome: there were 14 samples with failed transplants and 57 with functioning allograft.
We have demonstrated that IgG4 subclass was predictive of acute antibody mediated rejection (p=0.003) in the early post-transplant period. The multiple binary regression analysis has shown that the occurrence of the early rejection was due to 3 factors: total IgG4 MFI levels, the highest MFI DSA levels and the total number of HLA mismatches. For each additional mismatch there was 3.2 times increase in the odds of the transplant being rejected; 13% increase in the odds of the rejection for each 1000 units increase in MFI highest IgG; and per each 1000-unit increase in total IgG4 levels there was 30% increase in the odds of the transplant being rejected.
Long term graft survival times were also affected by the increased presence of the IgG4 subclass in pre-transplant samples: Kaplan-Meier survival analysis showed that death censored graft survival was significantly worse in cases with pre-transplant IgG4 positive compared to cases with negative IgG4 (p = 0.004). This conclusion is supported by the multivariate Cox proportional hazard method where 2 significant (p<0.05) factors (MFI highest IgG and presence of total IgG4 in pre-transplant samples) showed the hazard ratios of 161.218 and 5.945, respectively
These results highlight a clear link between the presence of IgG4 subclass in serum before transplantation and unwanted postoperative outcomes such as acute antibody mediated rejection and long term graft failure. Therefore, IgG4 can be additional biomarker that could be used to risk stratify kidney transplant recipients
Item Type: | Conference Item (Poster) | ||||
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Subjects: | Q Science > QP Physiology R Medicine > RD Surgery |
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Divisions: | Faculty of Science, Engineering and Medicine > Engineering > Engineering | ||||
Library of Congress Subject Headings (LCSH): | Graft rejection -- Prevention, Transplantation of organs, tissues, etc, Immune response | ||||
Official Date: | 2014 | ||||
Dates: |
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Status: | Peer Reviewed | ||||
Publication Status: | Unpublished | ||||
Access rights to Published version: | Restricted or Subscription Access | ||||
Conference Paper Type: | Poster | ||||
Title of Event: | Third International Transplantation conference : How much risk can you take and what to do if it all goes pear shaped. | ||||
Type of Event: | Conference | ||||
Location of Event: | University of Warwick, UK | ||||
Date(s) of Event: | 31 Oct -1 Nov 2014 | ||||
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