title: Predicted Indirectly Recognizable HLA Epitopes Presented by HLA-DRB1 Are Related to HLA Antibody Formation During Pregnancy.
abstract: Pregnancy can prime maternal immune responses against inherited paternal HLA of the fetus, leading to the production of child-specific HLA antibodies. We previously demonstrated that donor-specific HLA antibody formation after kidney transplantation is associated with donor-derived HLA epitopes presented by recipient HLA class II (predicted indirectly recognizable HLA epitopes presented by HLA class II [PIRCHE-II]). In the present study, we evaluated the role of PIRCHE-II in child-specific HLA antibody formation during pregnancy. A total of 229 mother-child pairs were HLA typed. For all mismatched HLA class I molecules of the child, we subsequently predicted the number of HLA epitopes that could be presented by maternal HLA class II molecules. Child-specific antigens were classified as either immunogenic or nonimmunogenic HLA based on the presence of specific antibodies and correlated to PIRCHE-II numbers. Immunogenic HLA contained higher PIRCHE-II numbers than nonimmunogenic HLA. Moreover, the probability of antibody production during pregnancy increased with the number of PIRCHE-II. In conclusion, our data suggest that the number of PIRCHE-II is related to the formation of child-specific HLA antibodies during pregnancy. Present confirmation of the role of PIRCHE-II in antibody formation outside the transplantation setting suggests the PIRCHE-II concept is universal.
authors.affiliation: Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: K
authors.initials: K
authors.lastname: Geneugelijk
authors.affiliation: Laboratory for Transplantation Immunology and Nephrology, Department of Biomedicine, University Hospital Basel, Basel, Switzerland.
authors.forename: G
authors.initials: G
authors.lastname: Hönger
authors.affiliation: Department of Theoretical Biology and Bioinformatics, University Utrecht, Utrecht, The Netherlands.
authors.forename: H W M
authors.initials: HW
authors.lastname: van Deutekom
authors.affiliation: Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: K A
authors.initials: KA
authors.lastname: Thus
authors.affiliation: Department of Theoretical Biology and Bioinformatics, University Utrecht, Utrecht, The Netherlands.
authors.forename: C
authors.initials: C
authors.lastname: Keşmir
authors.affiliation: Department for Obstetrics and Fetomaternal Medicine, University Hospital Basel, Basel, Switzerland.
authors.forename: I
authors.initials: I
authors.lastname: Hösli
authors.affiliation: Clinic for Transplantation Immunology and Nephrology, University Hospital Basel, Basel, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Schaub
authors.affiliation: Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Spierings
mesh_terms: D000917:Antibody Formation / Q000276:immunology*; D002648:Child; D015331:Cohort Studies; D000939:Epitopes / Q000276:immunology*; D005260:Female; D005500:Follow-Up Studies; D059811:HLA-DRB1 Chains / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D007518:Isoantibodies / Q000276:immunology*; D011247:Pregnancy; D011379:Prognosis; D014019:Tissue Donors
chemical_list: D000939:Epitopes; D059811:HLA-DRB1 Chains; D007518:Isoantibodies
keywords: antigen presentation/recognition; histocompatibility; obstetrics and gynecology; pregnancy; translational research/science