Human Leukocyte Antigen (HLA) Typing Study Identifies Maternal DQ2 Susceptibility Alleles among Infertile Women: Potential Associations with Autoimmunity and Micronutrients

Ilio Giambini,Sara Ferrigno,Paola Triggianese,Maria Sole Chimenti,Erica De Martino,Elisabetta Greco,Arianna D’Antonio,Paola Conigliaro,Carlo Perricone,Caterina De Carolis

doi:10.3390/nu13093270

Ilio Giambini, Sara Ferrigno + Show 8 more

Open Access

https://doi.org/10.3390/nu13093270

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Journal: Nutrients	Publication Date: Sep 19, 2021
Citations: 3	License type: CC BY 4.0

Affiliation: University of Rome Tor Vergata, University of Perugia

Abstract

Background. The interplay between female fertility and autoimmune diseases (AIDs) can involve HLA haplotypes and micronutrients. We analyzed the distribution of HLA-DQ2/-DQ8 in women with infertility or recurrent spontaneous abortion (RSA) and possible associations with AIDs and micronutrient status. Methods. Consecutive women (n = 187) with infertility and RSA, and controls (n = 350) were included. All women were genotyped for HLA-DQ2 (DQA1*0201, A1*05, and B1*02) and -DQ8 (DQA1*03 and DQB1*0302) alleles. Serum 25(OH)D, VB12, folate, and ferritin were evaluated. Results. DQA1*05/B1*02 and the occurrence of at least one DQ2 allele were more prevalent among RSA and infertile women than controls. Infertile women showed lower 25(OH)D and higher prevalence of AIDs than RSA women. In the multivariate analysis, DQA1*05/B1*02 was associated with a significantly higher risk of AIDs in infertile women, and DQA1*05 was independently associated with both 25(OH)D deficiency and AIDs. In RSA women, the presence of AIDs was associated with a significantly higher risk of 25(OH)D deficiency. Conclusion. Our findings showed, for the first time, a higher proportion of DQ2 alleles in infertile and RSA women as compared to controls. Predisposing DQ2 alleles are independent risk factors for AIDs and 25(OH)D deficiency in infertile women and could represent biomarkers for performing early detection of women requiring individually tailored management.

Highlights

Primary infertility and recurrent spontaneous abortion (RSA) are multifactorial conditions
We showed that Human Leukocyte Antigen (HLA)-DQ2/-DQ8 alleles have a similar prevalence in women with primary infertility compared to women with RSA
Our findings are in accordance with data reporting a significantly increased prevalence of HLA-DQ2-positivity in women with infertility and RSA compared to healthy controls, supporting a possible pathogenic link between these susceptibility

Summary

Introduction

Primary infertility and recurrent spontaneous abortion (RSA) are multifactorial conditions. 50% of RSA are related to chromosomal abnormalities, such as aneuploidy [1]. It is plausible that there are cases of RSA with other genetic association that are not currently routinely detected [1]. It is known that autoimmune diseases (AIDs) are associated with strong female preponderance and often present during the reproductive years [4]. Several systemic and organ-specific AIDs are associated with infertility and RSA [5,6]. Autoimmune thyroid diseases (AITD), including Hashimoto thyroiditis, can lead to pregnancyrelated adverse outcomes due to the direct and indirect effects of autoimmunity and/or mild/subclinical thyroid dysfunction [5,7]. AITD susceptibility is genetically driven [8]

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