Paternal HLA-Derived Epitopes and Live Birth in Secondary Recurrent Pregnancy Loss: New Insights From a Clinical Trial.
IVIG
PIRCHE‐II
T‐cell epitopes
recurrent pregnancy loss
Journal
HLA
ISSN: 2059-2310
Titre abrégé: HLA
Pays: England
ID NLM: 101675570
Informations de publication
Date de publication:
Oct 2024
Oct 2024
Historique:
revised:
18
07
2024
received:
21
11
2023
accepted:
01
10
2024
medline:
17
10
2024
pubmed:
17
10
2024
entrez:
17
10
2024
Statut:
ppublish
Résumé
Recurrent pregnancy loss (RPL), defined as two or more pregnancy losses before the 24th week of gestation, affects 1%-3% of women worldwide. Approximately, 40% of RPL cases are secondary RPL (sRPL), where women have given birth before facing pregnancy losses. The underlying causes of RPL remain unclear, but immune-related factors may play a role. Previously, a randomised controlled trial using immunoglobulin (IVIG) in sRPL women with a history of four pregnancy losses performed in our RPL unit did not show significant effects of IVIG treatment overall. Yet, some evidence suggests potential benefits for a subset of sRPL patients. In the cohort used for the randomised controlled trial, we examined the role of maternal HLA class II-presented fetal HLA-derived epitopes in sRPL using the predicted indirectly recognisable HLA epitopes (PIRCHE-II) algorithm. In the placebo group, sRPL mothers with an anti-HLA antibody response had higher PIRCHE-II scores when having a live birth compared with sRPL women who experienced another pregnancy loss. This difference was not observed in the IVIG-treated group. Furthermore, as a proxy for T-cell memory, the number of overlapping peptides between the two paternal haplotypes in couples having live births without treatment displayed a larger number of overlapping peptides. This effect was primarily driven by class II-derived peptides. These results suggest that specific combinations of sRPL mothers and fathers, particularly those with an anti-HLA antibody response, may generate higher PIRCHE-II scores, which could contribute to successful live births. Understanding these immune interactions may provide insights for personalised diagnostic and therapeutic strategies in sRPL.
Substances chimiques
Epitopes
0
Immunoglobulins, Intravenous
0
HLA Antigens
0
Histocompatibility Antigens Class II
0
Types de publication
Journal Article
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
e15723Subventions
Organisme : Svend Andersen Fonden
Organisme : Rigshospitalet
ID : E-22614-02
Organisme : Rigshospitalet
ID : E-22614-03
Organisme : Ferring Pharmaceuticals
Informations de copyright
© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Références
R. Bender Atik, O. B. Christiansen, J. Elson, et al., “ESHRE Guideline: Recurrent Pregnancy Loss: An Update in 2022,” Human Reproduction Open 2023, no. 1 (2023): hoad002, https://doi.org/10.1093/HROPEN/HOAD002.
O. B. Christiansen, E. C. Larsen, P. Egerup, L. Lunoee, L. Egestad, and H. S. Nielsen, “Intravenous Immunoglobulin Treatment for Secondary Recurrent Miscarriage: A Randomised, Double‐Blind, Placebo‐Controlled Trial,” BJOG: An International Journal of Obstetrics & Gynaecology 122, no. 4 (2015): 500–508, https://doi.org/10.1111/1471‐0528.13192.
O. B. Christiansen, A. M. Kolte, M. C. Krog, H. S. Nielsen, and P. Egerup, “Treatment With Intravenous Immunoglobulin in Patients With Recurrent Pregnancy Loss: An Update,” Journal of Reproductive Immunology 133 (February 2019): 37–42, https://doi.org/10.1016/j.jri.2019.06.001.
N. Sereshki, A. Andalib, A. Ghahiri, et al., “The Expression of Human Leukocyte Antigen by Human Ejaculated Spermatozoa,” Molecular Genetics & Genomic Medicine 7, no. 12 (2019): e1005, https://doi.org/10.1002/MGG3.1005.
D. W. Bianchi, G. K. Zickwolf, G. J. Weil, S. Sylvester, and M. A. Demaria, “Male Fetal Progenitor Cells Persist in Maternal Blood for as Long as 27 Years Postpartum,” Proceedings of the National Academy of Sciences of the United States of America 93, no. 2 (1996): 705–708, https://doi.org/10.1073/pnas.93.2.705.
M. J. Hoogduijn, M. Franquesa, H. Yeh, D. J. Firl, G. Benichou, and J. I. Kim, “A Paradigm Shift on the Question of B Cells in Transplantation?,” Recent Insights on Regulating the Alloresponse 8 (2017): 80, https://doi.org/10.3389/fimmu.2017.00080.
M. J. Bevan, “Helping the CD8+ T‐Cell Response,” Nature Reviews Immunology 4, no. 8 (2004): 595–602, https://doi.org/10.1038/nri1413.
K. Geneugelijk and E. Spierings, “PIRCHE‐II: An Algorithm to Predict Indirectly Recognizable HLA Epitopes in Solid Organ Transplantation,” Immunogenetics 72, no. 1–2 (2020): 119–129, https://doi.org/10.1007/S00251‐019‐01140‐X.
K. Geneugelijk, G. Hönger, H. W. M. Van Deutekom, et al., “Predicted Indirectly Recognizable HLA Epitopes Presented by HLA‐DRB1 Are Related to HLA Antibody Formation During Pregnancy,” American Journal of Transplantation 15, no. 12 (2015): 3112–3122, https://doi.org/10.1111/ajt.13508.
E. T. M. Peereboom, B. M. Matern, T. Tomosugi, et al., “T‐Cell Epitopes Shared Between Immunizing HLA and Donor HLA Associate With Graft Failure After Kidney Transplantation,” Frontiers in Immunology 12 (2021), https://doi.org/10.3389/FIMMU.2021.784040.
K. Geneugelijk, G. Hönger, H. W. M. van Deutekom, I. M. Hösli, S. Schaub, and E. Spierings, “A Previous Miscarriage and a Previous Successful Pregnancy Have a Different Impact on HLA Antibody Formation During a Subsequent Successful Pregnancy,” Frontiers in Immunology 7 (December 2016): 571, https://doi.org/10.3389/FIMMU.2016.00571.
L. Gragert, A. Madbouly, J. Freeman, and M. Maiers, “Six‐Locus High Resolution HLA Haplotype Frequencies Derived From Mixed‐Resolution DNA Typing for the Entire US Donor Registry,” Human Immunology 74, no. 10 (2013): 1313–1320, https://doi.org/10.1016/J.HUMIMM.2013.06.025.
R. M. Powell, D. Lissauer, J. Tamblyn, et al., “Decidual T Cells Exhibit a Highly Differentiated Phenotype and Demonstrate Potential Fetal Specificity and a Strong Transcriptional Response to IFN,” Journal of Immunology 199, no. 10 (2017): 3406–3417, https://doi.org/10.4049/JIMMUNOL.1700114.
S. Tsuda, A. Nakashima, T. Shima, and S. Saito, “New Paradigm in the Role of Regulatory T Cells During Pregnancy,” Frontiers in Immunology 10 (March 2019): 1–11, https://doi.org/10.3389/fimmu.2019.00573.
H. Beydoun and A. F. Saftlas, “Association of Human Leucocyte Antigen Sharing With Recurrent Spontaneous Abortions,” Tissue Antigens 65, no. 2 (2005): 123–135, https://doi.org/10.1111/J.1399‐0039.2005.00367.X.
T. Meuleman, L. E. L. O. Lashley, O. M. Dekkers, J. M. M. van Lith, F. H. J. Claas, and K. W. M. Bloemenkamp, “HLA Associations and HLA Sharing in Recurrent Miscarriage: A Systematic Review and Meta‐Analysis,” Human Immunology 76, no. 5 (2015): 362–373, https://doi.org/10.1016/J.HUMIMM.2015.02.004.
A. G. S. Van Halteren, E. Jankowska‐Gan, A. Joosten, et al., “Naturally Acquired Tolerance and Sensitization to Minor Histocompatibility Antigens in Healthy Family Members,” Blood 114, no. 11 (2009): 2263–2272, https://doi.org/10.1182/BLOOD‐2009‐01‐200410.
M. P. Dierselhuis, E. Jankowska‐Gan, E. Blokland, et al., “HY Immune Tolerance Is Common in Women Without Male Offspring,” PLoS One 9, no. 3 (2014): e91274, https://doi.org/10.1371/JOURNAL.PONE.0091274.
D. A. Kahn and D. Baltimore, “Pregnancy Induces a Fetal Antigen‐Specific Maternal T Regulatory Cell Response That Contributes to Tolerance,” Proceedings of the National Academy of Sciences of the United States of America 107, no. 20 (2010): 9299–9304, https://doi.org/10.1073/PNAS.1003909107.
S. Cai, S. Dai, R. Lin, et al., “The Effectiveness and Safety of Intrauterine Infusion of Autologous Regulatory T Cells (Tregs) in Patients With Recurrent Pregnancy Loss and Low Levels of Endometrial FoxP3+ Cells: A Retrospective Cohort Study,” American Journal of Reproductive Immunology 90, no. 2 (2023): e13735, https://doi.org/10.1111/AJI.13735.
D. J. Kim, S. K. Lee, J. Y. Kim, et al., “Intravenous Immunoglobulin G Modulates Peripheral Blood Th17 and Foxp3(+) Regulatory T Cells in Pregnant Women With Recurrent Pregnancy Loss,” American Journal of Reproductive Immunology 71, no. 5 (2014): 441–450, https://doi.org/10.1111/AJI.12208.
H. Yamada, M. Deguchi, S. Saito, et al., “High Doses of Intravenous Immunoglobulin Stimulate Regulatory T Cell and Suppress Natural Killer Cell in Women With Recurrent Pregnancy Loss,” Journal of Reproductive Immunology 158 (2023): 103977, https://doi.org/10.1016/J.JRI.2023.103977.
J. H. Rowe, J. M. Ertelt, L. Xin, and S. S. Way, “Pregnancy Imprints Regulatory Memory That Sustains Anergy to Fetal Antigen,” Nature 490, no. 7418 (2012): 102–106, https://doi.org/10.1038/NATURE11462.
T. Tomosugi, K. Iwasaki, S. Sakamoto, et al., “Clinical Significance of Shared T Cell Epitope Analysis in Early De Novo Donor‐Specific Anti‐HLA Antibody Production After Kidney Transplantation and Comparison With Shared B Cell Epitope Analysis,” Frontiers in Immunology 12 (2021): 621138, https://doi.org/10.3389/FIMMU.2021.621138/BIBTEX.
W. Wang, X. Zhou, Y. Zhang, et al., “The Characteristics of Antigenic Specificity of Memory Regulatory t Cells in Women With Unexplained Recurrent Pregnancy Loss,” Journal of Reproductive Immunology 154 (May 2022): 103694, https://doi.org/10.1016/j.jri.2022.103694.
L. E. E. L. O. Lashley, M. L. P. van der Hoorn, G. W. Haasnoot, D. L. Roelen, and F. H. J. Claas, “Uncomplicated Oocyte Donation Pregnancies Are Associated With a Higher Incidence of Human Leukocyte Antigen Alloantibodies,” Human Immunology 75, no. 6 (2014): 555–560, https://doi.org/10.1016/j.humimm.2014.02.016.
A. Senev, E. Van Loon, E. Lerut, et al., “Association of Predicted HLA T‐Cell Epitope Targets and T‐Cell‐Mediated Rejection After Kidney Transplantation,” American Journal of Kidney Diseases 80, no. 6 (2022): 718–729.e1, https://doi.org/10.1053/J.AJKD.2022.04.009.
M. G. H. Betjes, E. T. M. Peereboom, H. G. Otten, and E. Spierings, “The Number of Donor HLA‐Derived T Cell Epitopes Available for Indirect Antigen Presentation Determines the Risk for Vascular Rejection After Kidney Transplantation,” Frontiers in Immunology 13 (2022), https://doi.org/10.3389/FIMMU.2022.973968.
M. Niemann, B. M. Matern, E. Spierings, S. Schaub, and G. Hönger, “Peptides Derived From Mismatched Paternal Human Leukocyte Antigen Predicted to be Presented by HLA‐DRB1, ‐DRB3/4/5, ‐DQ, and ‐DP Induce Child‐Specific Antibodies in Pregnant Women,” Frontiers in Immunology 12 (December 2021): 1–12, https://doi.org/10.3389/fimmu.2021.797360.
H. Svarre Nielsen, A. M. Nybo Andersen, A. M. Kolte, and O. B. Christiansen, “A Firstborn Boy Is Suggestive of a Strong Prognostic Factor in Secondary Recurrent Miscarriage: A Confirmatory Study,” Fertility and Sterility 89, no. 4 (2008): 907–911, https://doi.org/10.1016/j.fertnstert.2007.04.029.
C. Nørgaard‐Pedersen, U. S. Kesmodel, and O. B. Christiansen, “Women With Recurrent Pregnancy Loss More Often Have an Older Brother and a Previous Birth of a Boy: Is Male Microchimerism a Risk Factor?,” Journal of Clinical Medicine 10, no. 12 (2021): 2613, https://doi.org/10.3390/jcm10122613.
H. S. Nielsen, F. Wu, Z. Aghai, et al., “H‐Y Antibody Titers Are Increased in Unexplained Secondary Recurrent Miscarriage Patients and Associated With Low Male: Female Ratio in Subsequent Live Births,” Human Reproduction 25, no. 11 (2010): 2745–2752, https://doi.org/10.1093/humrep/deq242.
S. Bliddal, U. Feldt‐Rasmussen, Å. K. Rasmussen, et al., “Thyroid Peroxidase Antibodies and Prospective Live Birth Rate: A Cohort Study of Women With Recurrent Pregnancy Loss,” 29, no. 10 (2019): 1465–1474, https://doi.org/10.1089/THY.2019.0077.
S. D'Ippolito, C. Ticconi, C. Tersigni, et al., “The Pathogenic Role of Autoantibodies in Recurrent Pregnancy Loss,” American Journal of Reproductive Immunology 83, no. 1 (2020): e13200, https://doi.org/10.1111/AJI.13200.
E. W. Triche, K. K. Harland, E. H. Field, L. M. Rubenstein, and A. F. Saftlas, “Maternal–Fetal HLA Sharing and Preeclampsia: Variation in Effects by Seminal Fluid Exposure in a Case–Control Study of Nulliparous Women in Iowa,” Journal of Reproductive Immunology 101 (2014): 111–119, https://doi.org/10.1016/J.JRI.2013.06.004.
K. Khosrotehrani, K. L. Johnson, J. Lau, A. Dupuy, D. H. Cha, and D. W. Bianchi, “The Influence of Fetal Loss on the Presence of Fetal Cell Microchimerism: A Systematic Review,” Arthritis and Rheumatism 48, no. 11 (2003): 3237–3241, https://doi.org/10.1002/ART.11324.
T. Schlaikjær Hartwig, L. Ambye, J. R. Gruhn, et al., “Cell‐Free Fetal DNA for Genetic Evaluation in Copenhagen Pregnancy Loss Study (COPL): A Prospective Cohort Study,” Lancet 401, no. 10378 (2023): 762–771, https://doi.org/10.1016/S0140‐6736(22)02610‐1.