Human leukocyte antigen (HLA) DQ2/DQ8 prevalence in recurrent pregnancy loss women

Antonio Gasbarrini, Giovanni Scambia, Nicoletta Di Simone, Silvia D'Ippolito, Roberta Castellani, Sandro Rocchetti

Risultato della ricerca: Contributo in rivistaArticolo in rivistapeer review

13 Citazioni (Scopus)

Abstract

OBJECTIVE: Over the last few years, medical scholars have reported the significant association between recurrent pregnancy loss (RPL) and celiac disease (CD). Various pathogenic mechanisms underlying the pregnancy failure in CD have been suggested: among them the ability of anti-transglutaminase antibodies to impair the trophoblast invasiveness and endometrial endothelial cells differentiation and disrupt early placentation. CD shows a complex non-Mendelian pattern of inheritance, involving major histocompatibility complex (MHC) genes. The strongest effects are mapped to the classical human leukocyte antigen (HLA)-DQA1 and HLA-DQB1 genes. Specifically, the common haplotypes DQ2.5, DQ2.2, and DQ8 have been shown to increase CD risk by six-fold on average. MHC region contains genes with immunological functions and is responsible for the strongest association signals observed in most immune-mediated diseases. The aim of our study was to investigate the prevalence of the HLA-DQ2/DQ8 haplotypes in RPL, outside of CD. METHODS: The study population included women with history of RPL (≥3 spontaneous pregnancy losses) and women with at least two previous uncomplicated term pregnancies (control group, CTR). All women gave their informed consent to use their data for research purposes. RESULTS: 97 RPL women and 55 CTR were considered in the study. Mean age of the RPL sample was 37.7 (standard deviation, SD, 3.0; min 27; max 39). Mean age of the control group was 35.6 (SD 3.0; min 26years; m, max 38). A significantly increased prevalence of HLA-DQ2/DQ8 haplotype positivity was found in RPL population compared to control women (52.6% vs 23.6%; p<0.01). CONCLUSIONS: Our observations show for the first time a higher proportion of individuals HLA DQ2/DQ8 positive in women with RPL as compared to controls (and to general population estimates). Further studies are needed to better understand (i) the possible pathogenic mechanism to this observation; (ii) the clinical and therapeutic implications of our observation in order to provide a new approach to RPL couples. Copyright © 2016. Published by Elsevier B.V. KEYWORDS: Celiac disease; Genetic susceptibility; Human leukocyte antigen (HLA)-DQ2/DQ8; Intestinal permeabylity; Recurrent pregnancy loss
Lingua originaleEnglish
pagine (da-a)638-643
Numero di pagine6
RivistaAUTOIMMUNITY REVIEWS
DOI
Stato di pubblicazionePubblicato - 2016

Keywords

  • Celiac disease
  • Genetic susceptibility
  • Human leukocyte antigen (HLA)-DQ2/DQ8
  • Intestinal permeabylity
  • Recurrent pregnancy loss

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