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. 2022 Dec 1;13:988370. doi: 10.3389/fimmu.2022.988370

Table 3.

Summary of the studies that reported the association of HLA-G polymorphisms with sHLA-G expression in patients attending IVF treatment.

Study Country Ethnicity Study population Number of patients tested Sample tested Timing of sample collection Type of assay sHLA-G isoform Detection limit Result Included in meta-analysis
Papúchová 2022 (41) Denmark Caucasian Women attending IVF treatment 121 Endometrium the day equivalent to embryo transfer IH HLA-G5 and HLA-G6 NR No significant differences were observed in sHLA-G expression between the different HLA-G genotypes No
Piekarska 2021 (76) Poland Caucasian Men attending IVF treatment 183 Seminal plasma 2-7 days of sexual abstinence ELISA HLA-G1 and HLA-G5 0.6 IU/ml Certain HLA-G haplotypes and diplotypes of rs1632947-rs1233334-rs371194629 are associated with seminal sHLA-G expression No
Nilsson 2020 (79) Denmark Caucasian Couples attending IVF treatment 127 couples and 4 single women Periphery blood plasma and seminal plasma NR ELISA HLA-G1 and HLA-G5 0.6 IU/ml HLA-G 14bp genotype or HLA-G 3’UTR diplotype is significantly associated with seminal sHLA-G levels, while is not significantly associated with female blood plasma sHLA-G levels Yes
Nowak 2020 (8) Poland Caucasian Women attending IVF 234 before IVF-ET and 185 after IVF-ET Periphery blood plasma Before and after IVF-ET ELISA HLA-G1 and HLA-G5 0.6 IU/ml Certain HLA-G haplotypes of rs1632947-rs1233334-rs371194629 are associated with sHLA-G expression in blood plasma before IVF-ET; whereas such observations were not detected after ET No
Craenmehr 2019 (77) Netherlands Caucasian Men attending IVF treatment 156 Seminal plasma NR ELISA HLA-G1 and HLA-G5 0.6 IU/ml Seminal plasma sHLA-G levels are associated with HLA-G SNPs (HLA-G 14 bp ins/del, +3003 C/T, +3010 C/G, +3142 C/G, +3187 A/G, +3196 C/G, +3496 A/G and + 3509 G/T) and haplotypes at the 3’UTR Yes
Nardi 2016 (35) Brazil Mixed RIF and control patients 58 Periphery blood serum NR ELISA HLA-G1 and HLA-G5 0.25ng/ml HLA-G 14bp del variant is associated with higher sHLA-G levels Yes
Dahl 2014 (78) Denmark Caucasian Couples attending IVF treatment 43 men for seminal test; 53 women and 47 men for blood test Seminal plasma and periphery blood plasma NR ELISA HLA-G1 and HLA-G5 0.6 IU/ml Male HLA-G 14bp del/del genotype is associated with higher sHLA-G levels in seminal plasma Yes
Nardi 2012 (19) Brazil Mixed RIF and control patients 41 RIF women and 60 controls Periphery blood serum NR ELISA HLA-G1 and HLA-G5 3.9U/ml HLA-G allele distribution in exon 2,3,4 is not associated with serum sHLA-G levels No
Sipak-Szmigiel 2007 (70) Poland Caucasian Women attending IVF treatment 80 Periphery blood plasma NR ELISA NR 2U/ml Allele HLA-G10101, 10102, and 10108 was related to higher plasma sHLA-G levels than other alleles No
Hviid 2004 (75) Denmark Caucasian Couples attending IVF treatment 43 women and 42 male partners Periphery blood serum Before pregnancy ELISA HLA-G1 and HLA-G5 1ng/ml Detectable sHLA-G in serum is restricted to HLA-G genotypes with the 14bp del No

IH, Immunohistochemical staining; ELISA, enzyme-linked immunosorbent assay; IVF, in vitro fertilization; ET, embryo transfer; 3’UTR, 3’ untranslated region; 5’ URR, 5’ upstream regulatory region; NR, not reported.