Lowe, D., Khovanova, N. A., Zehnder, Daniel, Higgins, R. D. and Briggs, D. (2012) Increased presence of complement fixing IgG isotypes and its association with acute rejection in antibody incompatible transplantation. In: The 23rd British Society for Histocompatibility and Immunogenetics Conference, Liverpool, U.K., May 28 - Jun 3, 2012. Published in: Tissue Antigens, Vol.79 (No.6). p. 505.

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Abstract

Donor specific antibodies (DSA) represent a risk factor for early antibody-mediated rejection and decreased allograft survival. However, local studies in antibody incompatible transplant (AiT) cases have shown that not all HLA-specific DSA are detrimental. Recent studies have shown that the analysis of pre-transplant DSA IgG subclass does not appear to predict development of acute rejection (Honger et al, 2011). Here we seek to show that changes in subclass composition to predict early rejection episodes in the acute post-transplant period. Fifty-one previous AiT cases were selected comprising 26 rejectors and 25 non-rejectors, with rejection diagnosed on the basis of clinical symptoms and/or histology. Daily serum samples were taken post-transplant with total level of HLA-specific IgG determined by single antigen bead assay. IgG1,2,3 and 4 HLA specific antibody levels were determined for all pretreatment, pretransplant and post-transplant peak samples. Samples taken prior to starting antibody removal therapy showed no difference between rejector and non-rejector groups in concordance with previously published data. However samples tested post-transplant at the time at which pan-IgG specific DSA peaked (days 8-11 post-transplant) clearly show an increase in the rejector group of donor-specific IgG1 (p = 0.01), and also the proportion of the total IgG response attributable to the complement fixing isotypes IgG1/IgG3 were greatly increased in the rejector group (p = 0.007). In addition the rejector group also showed a significant increase in donor specific IgG4 as the antibody response matured beyond 30 days posttransplant (p = 0.03). These data show a clear link between acute antibody mediated rejection (AMR) and the increased presence of complement fixing IgG isotypes. Increased levels of IgG4 associated with AMR may highlight progressive stimulation of the immune response, or immunoglobulin heavy chain class switching. Analysis of IgG subclass composition may be an important tool in the analysis of AMR in AiT.

Item Type:	Conference Item (Poster)
Subjects:	R Medicine > R Medicine (General)
Divisions:	Faculty of Science > Engineering
Journal or Publication Title:	Tissue Antigens
Publisher:	Wiley-Blackwell Publishing, Inc.
ISSN:	0001-2815
Date:	1 June 2012
Volume:	Vol.79
Number:	No.6
Page Range:	p. 505
Identification Number:	10.1111/j.1399-0039.2012.01877.x
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access
Conference Paper Type:	Poster
Title of Event:	The 23rd British Society for Histocompatibility and Immunogenetics Conference
Type of Event:	Conference
Location of Event:	Liverpool, U.K.
Date(s) of Event:	May 28 - Jun 3, 2012
URI:	http://wrap.warwick.ac.uk/id/eprint/46476

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