Predicted Indirectly ReCognizable HLA Epitopes presented by HLA-DRB1 (PIRCHE-II) are related to HLA-antibody formation during pregnancy

K. Geneugelijk, G. Hönger, H.W. van Deutekom, K.A. Thus, C. Kesmir, I. Hösli, S. Schaub, E. Spierings

Chair(s): dr. Dennis A. Hesselink, internist-nefroloog, Erasmus MC & dr. Marieke Roemeling, internist i.o., UMC Groningen

Wednesday 9 march 2016

16:00 - 16:10h at Zaal 1 & 2

Categories: Parallelsessie (klinisch)

Parallel session: Parallelsessie V - Klinisch

Pregnancy can prime maternal immune responses against inherited paternal HLA of the fetus. This frequently leads to the production of child-specific HLA antibodies. We previously showed that predicted T-helper epitopes derived from donor HLA and presented by recipient HLA class-II (PIRCHE-II) are associated with antibody response after kidney transplantation. The aim of this study is to evaluate the role of PIRCHE-II in the formation of child-specific HLA antibodies during pregnancy. A total of 301 mother-child pairs were HLA-typed and maternal blood samples were analyzed for the presence of child-specific HLA antibodies. Child-specific antigens were classified as either immunogenic HLA or non-immunogenic HLA based on the presence of specific antibodies and correlated to PIRCHE-II numbers. Immunogenic HLA contained higher numbers of PIRCHE-II than non-immunogenic HLA. Moreover, the probability of antibody production during pregnancy increased with the number of PIRCHE-II. However, this correlation was absent in pregnancies that were preceded by one or more miscarriages. Our data suggest that the number of PIRCHE-II is related to the formation of child-specific HLA antibodies during pregnancy. Furthermore, a previous miscarriage and a previous successful full-term pregnancy have a different immunological impact on a subsequent successful pregnancy. Present confirmation of the role of PIRCHE-II in antibody formation outside the transplantation setting suggests that the PIRCHE-II concept is universal.