Frequency and Determinants of Pregnancy-Induced Child-Specific Sensitization

Hönger, Gideon; Fornaro, Isabel; Granado, Cristina; Tiercy, Jean‐Marie; Hösli, Irène; Schaub, Stefan

doi:10.1111/ajt.12048

Cited by 69 publications

(76 citation statements)

References 18 publications

(54 reference statements)

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“…The peripheral blood samples and the cord blood samples were highresolution typed for the HLA-A, -B, -C and -DRB1 loci using DNA typing methodologies, as described previously (8).…”

Section: Hla Typingmentioning

confidence: 99%

“…This IPA-induced priming leads to the production of child-specific HLA antibodies in 10-30% of all pregnant women (4,(6)(7)(8). The frequency of HLA-specific antibody formation increases with the number of full-term pregnancies (6,9) and depends on the maternal and fetal HLA phenotype (10).…”

Section: Introductionmentioning

confidence: 99%

“…Currently, a redefined version of HLAMatchmaker identifies three-dimensional polymorphic amino acid patches located at the molecular surface of HLA molecules, designated as eplets (15). In addition, the number of mismatched eplets is correlated with HLA sensitization (8). Although considerable research has been devoted to predicting HLA-specific antibody formation, less research has been devoted to predicting the T cell reactivity involved in HLA antibody formation.…”

Section: Introductionmentioning

confidence: 99%

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Predicted Indirectly Recognizable HLA Epitopes Presented by HLA-DRB1 Are Related to HLA Antibody Formation During Pregnancy

Geneugelijk

Hönger

Deutekom

et al. 2015

American Journal of Transplantation

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† Contributed equally. ‡ Contributed equally.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.Abbreviations: IPA, inherited paternal HLA antigens; MFI, mean fluorescence intensity; PIRCHE-II, predicted indirectly recognizable HLA epitopes presented by HLA class II; SAB, single HLA antigen beads

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“…The peripheral blood samples and the cord blood samples were highresolution typed for the HLA-A, -B, -C and -DRB1 loci using DNA typing methodologies, as described previously (8).…”

Section: Hla Typingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Predicted Indirectly Recognizable HLA Epitopes Presented by HLA-DRB1 Are Related to HLA Antibody Formation During Pregnancy

Geneugelijk

Hönger

Deutekom

et al. 2015

American Journal of Transplantation

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“…No specific HLA-A antiboby was identified in our study. Indeed, the predominance of sensitization in the HLA-B locus might be related to its larger polymorphism compared to the other HLA loci [20,21]. This negative result could be explained by the sample size.…”

Section: Discussionmentioning

confidence: 99%

HLA Alloantibodies in Multiparous Women at Abidjan

Koffi¹

2016

IJI

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Serum of multiparous women can contain HLA polyclonal antibodies which can be used as reagents for serological typing of HLA class I and class II. The aim of this study was to investigate an alloimmunization of multiparous women and to identify HLA polyclonal antibodies which could be useful as laboratory reagents in view of the future HLA unit of the Department of Immunology at Abidjan. In an experimental and analytic study, we screened HLA antibodies using microlymphocytotoxicity test on sera of 121 multiparous women aged from 18 to 70 years old, in apparent good health, transfused or no-transfused and with at least two parities. 37.19% of the multiparous women were alloimmunized. 13 women were sensitized to HLA class I, 18 to HLA class II and 14 were both sensitized to class I and class II. Specificity of the screened antibodies was identified at 17.78%. HLA-B7 specificity (Class I) was 37.5% and class II specificity (HLA-DR4, DR7, DR13, DR13+14, DRw52) was 62.5%. Specificity was evaluated by the correlation coefficient. For class I specificity correlation coefficients were ranged from 0.79 to 1, while for class II specificities, correlation coefficients were ranged from 0.54 to 0.9. Screening of HLA antibodies on multiparous women at Abidjan was positive and specificities were determined. This enabled authors to the possibility of using multiparous women sera as a source of production of polyclonal antibodies for serological HLA typing in the HLA unit of the Department of Immunology at Abidjan.

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“…This is reflected by the formation of HLA alloantibodies to IPA in a significant proportion of parous women. [48][49][50] These antibodies are often directed against mismatched HLA-A, -B and -DR antigens, which are not expressed on trophoblast cells, the fetal cell layer which forms the border between mother and child. Therefore it is most likely that fetus-derived chimeric leukocytes are responsible for the induction of these alloantibodies.…”

Section: Pregnancy-induced Immunization and Fetal-maternal Microchimementioning

confidence: 99%