P232
Impact of pre-formed and de-novo MICA antibodies on renal allograft outcomes in
transplant recipients sensitised by pre-formed, donor-specific HLA antibody
Philippa Dodd, Michelle Willicombe, Paul Brookes, Eva Santos-Nunez, Nicola Gunby,
Konstantinos Koutrousos, Dawn Goodall, Candice Clarke, Rawya Charif, Jack Galliford,
Adam McLean, David Taube
Imperial College Renal & Transplant Centre, London, UK
Pre-formed, donor-specific antibodies directed at human leucocyte antigens (HLA) are
associated with antibody mediated rejection and inferior allograft outcomes. The MHC class Irelated chain A (MICA) are polymorphic gene sets closely linked to the HLA-B locus located
on chromosome 6, are expressed on a variety of cell types including endothelial cells and have
been considered a plausible target of an allograft response. However, their broad clinical
importance has not been clearly defined. The aim of this study was to determine the prevalence
of MICA antibody, the association between MICA and HLA antibodies and the effect of MICA
antibodies on renal allograft outcome.
We undertook a single centre, retrospective study to investigate MICA antibody status in
patients with pre-formed, donor-specific HLA antibodies who underwent renal transplantation
between 2006-2011 (n=63). Sera sampled immediately prior to-, at 3, 6 & 12 months posttransplantation and at rejection episodes were examined using LABScreen® Luminex® assay
technology. Additional data in respect to allograft function (serum creatinine), HLA mismatch,
HLA antibody status, donor type, rejection epsiodes and allograft failure were also collected.
Uni- and multivariate analyses were performed.
7.9% (5/63) recipients tested positive for pre-formed MICA antibody and remained positive
post-transplantation, 25.3% (16/63) devloped MICA antibody de novo and 66.6% (42/63) tested
negative for MICA antibody. Neither pre-formed or de novo MICA antibodies were
significantly associated with allograft rejection (p=0.52), survival (p=0.96) or function (p=0.34).
Pre-formed MICA anibodies may be associated with improved allograft survival up to 50
months post-transplantation after which this effect is lost. There was no significant association
between MICA antibodies and pre-transplant sensitisation with HLA class I (p=0.897), class II
(p=0.937) or class I+II (p=0.753) donor-specific antibodies.
Figure 1: Kaplan-Meier Survival Curve according to MICA antibody status
In this cohort of patients MICA antibodies, detected up to one year post transplantation, had no
impact on renal allograft outcomes. We recognise that this study is limited by cohort size and
lack of knowledge with regard to donor and recipient MICA genotypes.