HLA associations and HLA sharing in recurrent miscarriage: A systematic review and meta-analysis

• Published in: Human immunology Vol. 76; no. 5; pp. 362 - 373
• Main Authors: Meuleman, Tess, Lashley, Lisa E.L.O, Dekkers, Olaf M, van Lith, Jan M.M, Claas, Frans H.J, Bloemenkamp, Kitty W.M
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2015
• Subjects: Abortion, Habitual - genetics; Abortion, Habitual - immunology; Alleles; Allergy and Immunology; Female; Genetic Association Studies; Histocompatibility; Histocompatibility Antigens Class I - genetics; HLA alleles; HLA sharing; HLA-B Antigens - genetics; HLA-DRB1 Chains - genetics; HLA-E Antigens; Humans; Meta-analysis; Pregnancy; Recurrent miscarriage; Risk; Selection Bias; Systematic review; CDC; APS; sequence specific priming; Systematic review; complement dependent cytotoxicity; odds ratio; SLE; sequence specific oligonucleotides; recurrent miscarriage; restriction fragment length polymorphism; sequence based typing; systemic lupus erythematosus; two color fluorescence; HLA alleles; RFLP; OR; SBT; CI; rheumatoid arthritis; SSO; RA; HLA sharing; Meta-analysis; SSP; TCF; anti-phospholipid syndrome; confidence interval; RM; Recurrent miscarriage
• ISSN: 0198-8859; 1879-1166
• DOI: 10.1016/j.humimm.2015.02.004

Abstract Problem The aim of this meta-analysis was to evaluate whether specific maternal HLA alleles and HLA sharing of couples are associated with the occurrence of recurrent miscarriage (RM). Method of study A systematic literature search was performed for studies that evaluated the association between HLA alleles, HLA sharing and RM. RM was defined as three or more consecutive unexplained miscarriages and a control group was included of women with at least one live birth and no miscarriages in their history. Meta-analyses were performed and the pooled odds ratio (OR) was calculated. Results We included 41 studies. Selection bias was present in 40 studies and information bias in all studies. Meta-analyses showed an increased risk of RM in mothers carrying a HLA-DRB1*4 (OR 1.41, 95% CI 1.05–1.90), HLA-DRB1*15 (OR 1.57, 95% CI 1.15–2.14), or a HLA-E*01:01 allele (OR 1.47, 95% CI 0.20–1.81), and a decreased risk with HLA-DRB1*13 (OR 0.63, 95% CI 0.45–0.89) or HLA-DRB1*14 (OR 0.54, 95% CI 0.31–0.94). Pooling results for HLA sharing showed that HLA-B sharing (OR 1.39, 95% CI 1.11–1.75) and HLA-DR sharing (OR 1.57, 95% CI 1.10–1.25) were both associated with the occurrence of RM. Conclusion Although the present systematic review and meta-analysis demonstrates that specific HLA alleles and HLA sharing are associated with RM, a high degree of bias was present and therefore observed results should be interpreted carefully.