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Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

The Effect of Mechanical Circulatory Support on HLA Antibodies and Antibody-Mediated Rejection in Cardiac Allografts

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Introduction: Due to the shortage of donor organs, mechanical circulatory support systems (MCS) are now widely used as a treatment option to bridge the failing heart to transplant. It has been observed that MCS patients show a higher frequency of antibody-mediated rejection (AMR) episodes. The latter is thought to represent an immune reaction directed against the device in terms of allosensitation.

Hypothesis: Capillary C4d and/or C3d depositions are required to diagnose AMR in cardiac allografts. We aimed to analyze the effect of MCS on pre- and post-HTx HLA antibodies and their correlation to cardiac AMR with due regards to capillary C3d and C4d depositions.

Methods: We evaluated all consecutive right ventricular protocol endomyocardial biopsies (EMBs) of cardiac allografts which fulfilled the ISHLT- criteria (254 patients) during two consecutive calendar years. With regards to pre- transplant MCS treatment patients were divided into two groups (MCS group n=82 patients, non MCS group n= 138 patients). Conventional histology and immunohistochemical stains were used on formalin-fixed paraffin-embedded tissue sections (FFPE) to evaluate the EMBs regarding AMR (complements C3d and C4d). Permutation test (x2) was performed to analyze the relationship between C4d and C3d and pre-and post-transplant HLA-antibodies, measured using Luminex assay, in all patient subgroups. Cochran-Mantel-Haenzsel was performed to assure the significance of the difference of interactions in both tables.

Results: The statistical analysis showed in the MCS group a highly significant positive correlation between C3d and Pre-Tx-HLA (p=0.012, Pre-Tx-HLA Class I and II p= 0.042, respectively vs p=0.884 and p=0.349 in non-MCS group), which levelled out following HTx (p= 0.867 and 0.697 for HLA Class I and II, vs p=0.212 and p=0.682 in non-MCS group, respectively). Statistical significance was not reached between C4d and pre-or post Tx HLA-antibodies in any group (p=0.349 vs. p=0.694 for entire study population).

Conclusions: We demonstrated that C3d correlates solely in the MCS group with pre-Tx HLA antibodies and could therefore add to the diagnosis of AMR if the pre-transplant treatment is being considered in the diagnostic setting.
OriginalsprogEngelsk
Publikationsdatonov. 2018
StatusUdgivet - nov. 2018

ID: 56439236