EditorialAutoimmunity in Reproductive Health and Pregnancy

Jacek Tabarkiewicz ,1,2 Senthamil R. Selvan ,3 and Nathalie Cools4

1Department of Human Immunology, Faculty of Medicine, University of Rzeszów, Rzeszów, Poland2Centre for Innovative Research in Medical and Natural Sciences, Faculty of Medicine, University of Rzeszów, Rzeszów, Poland3Omni Array Biotechnology, Rockville, MD 20855, USA4Immune Regulation & Tolerance-Inducing Strategies (IRiS) Research Group, University of Antwerp, Antwerp, Belgium

Correspondence should be addressed to Jacek Tabarkiewicz; jacek.tabarkiewicz@gmail.com

Received 2 January 2018; Accepted 2 January 2018; Published 13 February 2018

Copyright © 2018 Jacek Tabarkiewicz et al. This is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in anymedium, provided the original work is properly cited.

The influence of pregnancy on the maternal immune sys-tem is complex and orchestrated by multiple hormonaland metabolic factors provided by the mother as well asthe fetus. The modifications of the maternal immuneresponse include changes in cell proportions, phenotypes,and their functional ability to produce cytokines and othermediators. During pregnancy, activations of pro- and anti-inflammatory responses are fluently regulated dependingon the phase of pregnancy [1]. Implantation, placentation,and delivery phases are proinflammatory, while the period ofrapid fetal growth and development is anti-inflammatory [1].The model of “immune suppression” during pregnancy hasbeen long accepted, yet at the present, we are aware that fetaltolerance is not caused by suppression of the maternalimmune system but rather by immunomodulation and thatpregnant women are very much capable of having robustimmune responses [2]. An understanding of the balancebetween tolerance and protection of the fetus and maternalactive immune response against pathogens or self-antigensmay contribute to developing new approaches to the problemof autoimmunity in reproductive health and pregnancy.

Autoimmune diseases are characterized by organ andtissue damage caused by self-reactive immune responsesmediated by antibodies and/or T cells. These diseases maybe associated with genetic and/or environmental predisposi-tions. Thus, autoimmune disorders predominantly affectwomen and often occur during reproductive years and have

implications for fertility and pregnancy to some extent [3, 4].The relationships between autoimmunity and reproductioninclude the impact of pregnancy on the clinical course ofautoimmune disorders as well as the influence of autoimmu-nity on pregnancy development. Thus, in this populationof patients, specialized concerns in pregnancy planning andmanagement are commonly encountered. Autoimmunediseases are usually thought to be associated with pathogenicactivity of Th17-/Th1-type cells; during pregnancy, Th2-typecytokines are noted to be crucial to maintain the tolerance ofthe mother towards the fetal semiallograft [3, 4]. In preg-nancy, immunoregulatory cytokines and cells are present inthe mother’s circulatory system and accumulate in thedecidua and can modify autoimmune responses influencingthe symptoms of autoimmune disease.

Systemic lupus erythematosus (SLE), primary antipho-spholipid syndrome (APS), and secondary SLE-associatedAPS affect mostly women of childbearing age [5]. In a paperby Andreoli et al., we found the most current recommenda-tions of the European League Against Rheumatism (EULAR)for women’s health issues in SLE and/or APS that weredeveloped using an evidence-based approach followed byan expert consensus [5]. The considerations in the expertconsensus were as follows: family planning, reduction ofthe risks of adverse maternal or fetal outcomes, use of hor-monal contraception and menopause replacement therapy,fertility preservation during therapy, assisted reproduction

HindawiJournal of Immunology ResearchVolume 2018, Article ID 9501865, 3 pageshttps://doi.org/10.1155/2018/9501865

techniques, importance of disease activity assessment, fetalmonitoring, risk of gynecological malignancies associatedwith exposure to immunosuppressive drugs, and humanpapillomavirus immunization.

In this special issue, original research articles will focuson the most recent advances on the influence of autoanti-bodies on fertilization, the impact of SLE, APS, and endome-triosis on pregnancy.

The anticentromere antibody (ACA) could impair oocytematuration potential and early embryonic development, butthe mechanisms of this pathology are still unknown. Thus,Y. Ying et al. conducted a preliminary exploration to deter-mine if ACA could penetrate into living mouse embryosand impair their developmental potential. An immunofluo-rescence assay was performed to determine penetration ofpolyclonal anticentromere antibodies in the embryos. Theyshow that anti-CENP-A antibody binds to the nucleus ofexposed embryos which results in significant growthimpairment. These novel results based on in vitro observa-tions provide a direction for studies considering mecha-nisms of ACA influence on embryos and confirmation ofthese findings in in vivo studies.

Antinuclear antibodies (ANAs), including anti-dsDNAantibodies, could be associated with infertility, a decline ofoocyte quality and impairment of embryo development,recurrent spontaneous abortion, and in vitro fertilization(IVF) failure. Research by J. Fan and colleagues exploredwhether the anti-dsDNA antibody could adversely affectreproductive outcomes. A total of 259 women receivingin vitro fertilization-embryo transfer cycle (IVF) wereenrolled in this study including women positive for ANAand anti-dsDNA, positive for ANA and negative anti-dsDNA, and negative for ANA and anti-dsDNA. They com-pared the number of retrieved oocytes, available embryos andhigh-quality embryos, rates of implantation, clinical preg-nancy and abortion among three groups in fresh embryotransfer, and frozen-thawed embryo transfer cycles, respec-tively. The authors found that all pregnant patients suf-fered from abortion in the ANA+/anti-dsDNA+ groupwhich suggests the need of new approaches to understandthe role of autoantibodies, especially the involvement ofanti-dsDNA, in reproductive outcomes.

Systemic lupus erythematosus is a chronic, multisystemautoimmune disease mostly affecting females of childbearingage and provides challenges in the prepregnancy, antenatal,intrapartum, and postpartum periods for patients and themedics providing care. S. J. Kroese and coauthors had theopportunity to pool data from the rheumatology and obstet-ric departments of two tertiary centers during a 16-yearperiod. They investigated SLE disease activity before, during,and after pregnancy. Moreover, they examined maternal andperinatal complications in this population, antiphospholipidantibody status, pregnancy complications, and the totalnumber of live births from SLE patients. The authors con-cluded that in the examined SLE population, the incidenceof maternal and perinatal complications is high comparedto the reported rates in the general population, irrespectiveof antiphospholipid antibody status, and despite low diseaseactivity before, during, and after pregnancy. These results

obtained during long period observational study could be ofadditional value in the counseling of SLE patients.

Therapy of rheumatic disorders with antimalarials,especially hydroxychloroquine (HCQ), is well confirmed.The research paper authored by S. J. Kroese et al. investi-gates if HCQ treatment during pregnancy in women withSLE is associated with improved pregnancy outcomes. Theanalyzed data was obtained at the University Medical Cen-ter Utrecht between 2000 and 2015, and sixty-three SLEpatients were included. Hydroxychloroquine use was asso-ciated with longer pregnancy duration in the vulnerablepreterm birth population, underscoring a beneficial effectof HCQ use during pregnancy. However, the authors statethat retrospective and observational character of theirstudy could be its limitation.

Antiphospholipid syndrome is a leading acquired causeof thrombosis and pregnancy loss. High mobility group box1 (HMGB1) is nuclear protein which organizes DNA andregulates transcription. Furthermore, HMGB1 could play apivotal role in chronic inflammation and autoimmune dis-eases. In the manuscript “Elevated Serum Level of HMGB1in Patients with the Antiphospholipid Syndrome” by V.Manganelli et al., the authors described that HMGB1/sRAGEmay play a pathogenic role in recurrent abortion in primaryand secondary APS. They analyzed sera from 30 patientswith antiphospholipid syndrome (11 primary and 19 second-ary APS), 35 subjects with pregnancy morbidity, and 30healthy females for HMGB1 and its putative receptor RAGE(sRAGE) as well as for TNF. The authors suggest that moni-toring HMGB1/sRAGE together with other prognosticparameters represents a useful tool to evaluate risk stratifi-cation in prevention of adverse pregnancy outcomes andfurther studies are warranted.

Endometriosis (EMS) is a common gynecologic diseasewhich could be associated with infertility in women. Therole of menstruation back flow planting and defects inthe immune system in the pathogenesis of EMS are wellestablished and widely accepted. Currently, we know thatendometriosis shares similarities with autoimmune disor-ders, which include elevated levels of cytokines, decreasedapoptosis, autophagy, and cell-mediated pathologies. Intheir original research paper, M. Gogacz et al. demonstratethat in patients with EMS, peritoneal fluid (PF) macro-phages express CD95+ at a significantly higher level thanin a nonendometriotic group. Moreover, the concentrationof the soluble form of Fas in PF of patients with moderateand severe endometriosis was significantly higher when com-pared to controls. The authors suggest that in the peritonealcavity of patients with EMS, a local immune responsecould not be effective in elimination of misplaced endome-trial cells because of increased apoptosis of immune cellslike macrophages.

In summary, this special issue covers many importantaspects of bidirectional associations between autoimmunityand reproductive health and pregnancy. We hope that thisspecial issue can provide valuable information to researchersas well as clinicians and lead not only to enhancement ofknowledge but also to serve for developing better care ofpregnant patients with autoimmune diseases.

2 Journal of Immunology Research

Acknowledgments

We would like to thank all the authors for the quality of theirsubmissions that will provide useful insights into the currentstate of the field. We would also like to express our greatappreciation to all the special issue reviewers and editors,whose efforts substantially contributed to the improvementof the overall quality of this thematic issue.

Jacek TabarkiewiczSenthamil R. Selvan

Nathalie Cools

References

[1] G. Mor and I. Cardenas, “The immune system in pregnancy: aunique complexity,” American Journal of Reproductive Immu-nology, vol. 63, no. 6, pp. 425–433, 2010.

[2] K. Racicot, J. Y. Kwon, P. Aldo, M. Silasi, and G. Mor,“Understanding the complexity of the immune system duringpregnancy,” American Journal of Reproductive Immunology,vol. 72, no. 2, pp. 107–116, 2014.

[3] M. P. Piccinni, L. Lombardelli, F. Logiodice, O. Kullolli,P. Parronchi, and S. Romagnani, “How pregnancy can affectautoimmune diseases progression?,” Clinical and MolecularAllergy, vol. 14, no. 1, p. 11, 2016.

[4] W. Marder, E. A. Littlejohn, and E. C. Somers, “Pregnancy andautoimmune connective tissue diseases,” Best Practice &Research Clinical Rheumatology, vol. 30, no. 1, pp. 63–80, 2016.

[5] L. Andreoli, G. K. Bertsias, N. Agmon-Levin et al., “EULAR rec-ommendations for women’s health and the management offamily planning, assisted reproduction, pregnancy and meno-pause in patients with systemic lupus erythematosus and/orantiphospholipid syndrome,” Annals of the Rheumatic Diseases,vol. 76, no. 3, pp. 476–485, 2017.

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