Antigenic targets of local antibodies produced in Ectopic Lymphoid Structures in Cardiac Allografts

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M.M.H. Huibers, J.M.T. Beerthuijzen, A.J. Gareau, E. Siera-de Koning, J. van Kuik, E.G. Kamburova, N. de Jonge, T.D.G. Lee, H.G. Otten, R.A. de Weger

Chair(s): dr. Hennie G. Otten, medisch immunoloog, UMC Utrecht & dr. Laura B. Bungener, medisch immunoloog, UMC Groningen

Thursday 10 march 2016

10:00 - 10:10h at Zaal 1 & 2

Categories: Parallelsessie (basaal)

Parallel session: Parallelsessie VII - Basaal immunologie

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Background:
Cardiac allograft vasculopathy (CAV) is an immune-mediated vascular pathology that limits the survival of cardiac transplants; antibody and cellular-mediated events have been implicated in this process. Ectopic lymphoid structures (ELS) surrounding coronary arteries can be observed in patients with evident CAV and are active, antibody-producing immune structures. The aim of this study was to investigate the antigenic targets of the antibodies produced in the ELS.

Methods:
Epicardial coronary arteries (n=56) were collected on autopsy from heart transplant patients and studied for the presence of ELS. Double immunohistochemistry was done to test whether plasma cells were positive for IgG and IgM antibodies. Clonality of plasma cells was tested using PCR and in situ hybridisation for kappa and lambda. IgG and IgM levels in tissue lysates of ELS were measured by ELISA, and typed for donor specificity using the Luminex platform. 

Results:
Plasma cells within and around ELS produce IgG or IgM antibodies. The B cells display an oligoclonal distribution. IgG and IgM levels in epicardial tissue were detected in explanted hearts (controls) but were significantly higher in cardiac transplant patients with large ELS (p<0.05). In 4 out of the 25 lysates from patients with ELS (16%) these contain donor specific antibodies directed towards HLA type II. In some cases HLA antibodies in the ELS were found, but not in the plasma/serum, suggesting local production instead of diffusion into the tissue.

Conclusion:
Patients with ELS exhibit actively antibody producing plasma cells with no clonal expansion. Interestingly, these locally produced antibodies are in some cases directed against the donor HLA-II type. Local antibody-mediated rejection has major consequences for the graft that might be hard to detect in the systemic circulation.