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

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.

Association between serum vitamin D level during pregnancy and recurrent spontaneous abortion: A systematic review and meta‐analysis

“…Fourteen studies [11][12][13][14][15][16][17][18][19][20][21][22][23][24] were included with serum vitamin D levels as a continuous variable. Twelve studies [11][12][13][14][15][16]18,19,[21][22][23][24]…”

“…Fourteen studies 11–24 were included with serum vitamin D levels as a continuous variable. Twelve studies 11–16,18,19,21–24 were included with serum vitamin D levels as a dichotomous variable. Meta‐analysis of the random effects model showed RSA patients had lower vitamin D levels during pregnancy than controls ( SMD = ‐1.48, 95% CI : ‐2.01, ‐.94, P < .001), and pregnant women with VDD had a higher risk of developing RSA than pregnant women with normal vitamin D ( OR = 4.02, 95% CI : 2.23, 7.25, P < .001).…”

“…Fifth, the study found that VDD is correlated with the development of autoimmune thyroid disease (AITD). 13,34,42 The mechanism might be that the decrease in vitamin D levels caused an increase in anti-TPO levels. 43 And high anti-TPO levels are a risk factor for early miscarriage.…”

“…10 However, considerable heterogeneity in the association between serum vitamin D and RSA was observed. [11][12][13][14][15][16][17][18][19][20][21][22][23][24] The aim of this review is to conduct a systematic synthesis and a metaanalysis of the evidence for the association between serum vitamin D levels and RSA.…”

“…The mechanism might be that changes in serum vitamin D concentrations could affect the levels of peripheral natural killer (NK) cells, regulatory T cells and helper T cells in pregnant women, as well as the levels of cytokines such as anti‐phospholipid antibodies (APA), thyroid peroxidase antibodies (anti‐TPO), anti‐nuclear antibodies (ANA) and anti‐single‐stranded DNA 10 . However, considerable heterogeneity in the association between serum vitamin D and RSA was observed 11–24 . The aim of this review is to conduct a systematic synthesis and a meta‐analysis of the evidence for the association between serum vitamin D levels and RSA.…”