Contents lists available at ScienceDirect Human Immunology journal homepage: www.elsevier.com/locate/humimm HLA-G and vertical mother-to-child transmission of human papillomavirus infection Karolina Louvanto a,b,c, ⁎ , Michel Roger d , Marie-Claude Faucher d , Kari Syrjänen a,e , Seija Grenman a , Stina Syrjänen c,f a Department of Obstetrics and Gynaecology, Turku University Hospital, University of Turku, Kiinanmyllynkatu 13, 20520 Turku, Finland b Wolfson Institute of Preventive Medicine, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK c Department of Oral Pathology and Radiology, University of Turku, Lemminkäisenkatu 2, 20520 Turku, Finland d Centre de Recherche du CHUM et Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, 2900, boul. Édouard-Montpetit, Montréal H3T 1J4, Canada e Department of Clinical Research, Biohit Oyj, Laippatie 1, 00880 Helsinki, Finland f Department of Pathology, Turku University Hospital, Kiinanmyllynkatu 10, 20520 Turku, Finland ARTICLE INFO Keywords: HLA-G Human papillomavirus Vertical transmission Mother Newborn ABSTRACT Role of host factors in transmission of human papillomavirus (HPV)-infection from mother to her offspring is not known. Our aim was to study whether human leukocyte antigen (HLA)-G allele concordance among the mo- ther–child pairs could facilitate vertical transmission of HPV, because HLA-G may contribute to immune tol- erance in pregnancy. Altogether, 310 mother-child pairs were included from the Finnish Family HPV study. Overall, nine different HLA-G alleles were identified. The HLA-G genotype concordance of G * 01:01:01/01:04:01 increased the risk of high risk (HR)-HPV genotype positivity in cord blood and infant’s oral mucosa. The mother- child concordance of G * 01:01:02/01:01:02 increased the risk of oral HPV positivity with HR-HPV genotypes both in the mother and offspring; OR 2.45 (95%CI 1.24–4.85). Discordant HLA-G allele for G * 01:04:01 and for G * 01:06 was significantly associated with infant’s oral low risk (LR)-HPV at birth, OR 3.07 (95%CI 1.01–9.36) and OR 5.19 (95%CI 1.22–22.03), respectively. HLA-G had no association with HPV genotype-specific con- cordance between the mother and child at birth nor influence on perinatal HPV status of the child. Taken together, our results show that HLA-G molecules have a role in predicting the newborn’s likelihood for oral HPV infection at birth. 1. Introduction Human papillomavirus (HPV) infection is one of the most common sexually transmitted infection (STI) worldwide [1]. The prevalence is shown to be highest among women and men around their sexual debut, and nearly all sexually active women and male will be infected with HPV in their lifetime [1,2]. However, HPV-infection can be transmitted in early life by vertical transmission from a mother to her child [3–6]. This transmission could occur in fertilization, during pregnancy (pre- natal), at delivery or during the perinatal period [3,4]. Acquisition of HPV-infections in early life is most likely dependent on a combination of epigenetic, immune and genetic factors of the child acting in concert with endogenous and exogenous co-factors and viral load [7]. Most HPV-infections among adults are transient, whereas infections in early life may lead to long-term consequences such as HPV-related cancer [3,8,9]. If HPV-infections are acquired in early life, this will certainly impact the protective effect of prophylactic HPV vaccines (currently given to adolescent girls) which should be considered while designing the future policies of vaccination and screening programs. Human Leukocyte Antigen (HLA)-G interferes with HPV-infection; its prevalence, persistence and progression to cervical cancer [10–13]. HLA-polymorphism influences the innate and adaptive immune re- sponse by antigen presentation and are crucial to the cell-mediated immune (CMI) response by clearing the virus [14]. These different HLA- types are divided into classical and non-classical, where HLA-G alleles represent the non-classical class Ib [15]. HLA-G is highly tissue-specific and has a very low degree of polymorphism compared to the other HLA- molecules [16]. Recent studies have revealed HLA-G to play a https://doi.org/10.1016/j.humimm.2018.03.002 Received 18 October 2017; Received in revised form 6 March 2018; Accepted 6 March 2018 ⁎ Corresponding author at: Department of Obstetrics and Gynecology, Turku University Hospital, University of Turku, Kiinanmyllynkatu 4-8, 20521 Turku, Finland. E-mail addresses: karolina.louvanto@utu.fi (K. Louvanto), michel.roger.chum@ssss.gouv.qc.ca (M. Roger), marie-claude.faucher.chum@ssss.gouv.qc.ca (M.-C. Faucher), kari.syrjanen@biohit.fi (K. Syrjänen), seija.grenman@tyks.fi (S. Grenman), stina.syrjanen@utu.fi (S. Syrjänen). Abbreviations: HPV, human papillomavirus; HLA, human leukocyte antigen; STI, sexually transmitted infection; HR, high-risk; LR, low-risk; FFHPV cohort, Finnish Family HPV cohort; PCR, polymerase chain reaction; CMI, cell-mediated immune Human Immunology xxx (xxxx) xxx–xxx 0198-8859/ © 2018 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved. Please cite this article as: Louvanto, K., Human Immunology (2018), https://doi.org/10.1016/j.humimm.2018.03.002