The HLA-G genotype is potentially associated with idiopathic recurrent spontaneous abortion

The causes for recurrent spontaneous abortion (RSA) remain unknown in a lar ge proportion of the cases. Human leukocyte antigen (HLA)-G and HLA-E are e xpressed on invasive trophoblast cells, and are supposed to confer to mater no-fetal tolerance. A total of 14 different nucleotide sequences have been described for HLA-G, including one dysfunctional null allele (HLA-G*0105N), while five different sequences have been described for HLA-E, In this stud y, 78 RSA couples and 52 fertile controls were typed for HLA-G and HLA-E by direct sequencing or single strand conformational polymorphism (SSCP) resp ectively. The overall analysis showed no significant difference in allele f requencies for either HLA-G or HLA-E between the two groups. However, HLA-G allele frequencies in women who had suffered from five or more RSA differe d significantly from fertile controls (P = 0.001), and from women who had u ndergone three or four RSA (P = 0.027). Detailed analysis demonstrated a si gnificant increase in the proportion of the HLA-G alleles *01013 and *0105N in the whole group of RSA women compared with fertile controls (P = 0.007) . When studying the prognostic value of HLA genotyping for pregnancy outcom e (n = 41), 31 patients (76%) gave birth to a living child without performi ng immunotherapy, Seven out of 10 (70%) couples suffering from a further RS A carried the HLA-G*01013 or *0105N allele, compared with 10 out 31 (32%) c ouples giving birth (P = 0.06). This study suggests that the HLA-G genotype may be a contributing factor in RSA.