title: A Previous Miscarriage and a Previous Successful Pregnancy Have a Different Impact on HLA Antibody Formation during a Subsequent Successful Pregnancy.
abstract: Inherited paternal HLA antigens from the semi-allogeneic fetus may trigger maternal immune responses during pregnancy, leading to the production of child-specific HLA antibodies. The prevalence of these HLA antibodies increases with the number of successful pregnancies. In the present study, we investigated the effect of a single prior miscarriage on HLA antibody formation during a subsequent successful pregnancy. Women with a successful pregnancy with one or more prior miscarriages (n= 229) and women with a successful pregnancy without a prior miscarriage (n= 58), and their children were HLA typed. HLA antibody analyses were performed in these women to identify whether HLA antibodies were formed against mismatched HLA class-I antigens of the last child. The percentage of immunogenic antigens was significantly lower after a single successful pregnancy that was preceded by a single miscarriage (n= 18 women) compared to a successful pregnancy that was preceded by a first successful pregnancy (n= 62 women). Thus, our data suggest that a previous miscarriage has a different impact on child-specific HLA antibody formation during a subsequent successful pregnancy than a previous successful pregnancy. The lower immunogenicity in these women cannot be explained by reduced numbers of immunogenic B-cell and T-cell epitopes. In conclusion, our observations indicate that increasing gravidity is not related to an increased prevalence of HLA antibodies in a single successful pregnancy that was preceded by a single prior miscarriage.
authors.affiliation: Laboratory for Translational Immunology, University Medical Center Utrecht , Utrecht , Netherlands.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Geneugelijk
authors.affiliation: Laboratory for Transplantation Immunology and Nephrology, Department of Biomedicine, University Hospital Basel , Basel , Switzerland.
authors.forename: Gideon
authors.initials: G
authors.lastname: Hönger
authors.affiliation: Department of Theoretical Biology and Bioinformatics, University Utrecht , Utrecht , Netherlands.
authors.forename: Hanneke Wilhelmina Maria
authors.initials: HW
authors.lastname: van Deutekom
authors.affiliation: Department for Obstetrics and Fetomaternal Medicine, University Hospital Basel , Basel , Switzerland.
authors.forename: Irene Mathilde
authors.initials: IM
authors.lastname: Hösli
authors.affiliation: Clinic for Transplantation Immunology and Nephrology, University Hospital Basel , Basel , Switzerland.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schaub
authors.affiliation: Laboratory for Translational Immunology, University Medical Center Utrecht , Utrecht , Netherlands.
authors.forename: Eric
authors.initials: E
authors.lastname: Spierings
keywords: HLA antibodies; PIRCHE-II; allo-sensitization; miscarriage; pregnancy