RESUMO
PROBLEM: Recurrent spontaneous abortion (RSA) is defined by at least three consecutive abortions in otherwise healthy couples. Paternal lymphocyte alloimmunization therapy (PLAT) is an effective therapy for RSA in some cases, but there are no predictive markers about the effectiveness of PLAT. METHOD OF STUDY: Forty-two consecutive cases with primary RSA treated by PLAT and 23 controls were the subjects. Polymorphisms of human leukocyte antigen (HLA)-E, HLA-G, HLA-A, HLA-B, HLA-C and HLA-DRB1 were investigated by sequenced based typing. Promoter polymorphism and a 14 bp ins/del polymorphism in exon 8 were also investigated for HLA-G. RESULTS: Thirty-eight RSA wives became pregnant within 1 year after PLAT. Among them, 27 obtained babies (succeeded PLAT cases), while 11 again aborted with no detectable chromosomal abnormalities in the aborted fetuses (aborted PLAT cases). The frequencies of HLA-G*010401, A*2402, B*5201, and DRB1*1502 were significantly increased in the aborted cases than those in the succeeded cases or controls. Of note, HLA-G*010401 was found in all aborted cases whereas it was found in 51.9% of succeeded cases (odds ratio = 21.4, P = 0.006, P(c) = 0.03), and the presence of HLA-G*010401 could predict the abortion after PLAT with sensitivity and specificity of 100% and 48.1%, respectively. CONCLUSION: Human leukocyte antigen testing may be useful for predicting effectiveness of PLAT in RSA.
Assuntos
Aborto Habitual/terapia , Antígenos HLA/genética , Antígenos de Histocompatibilidade Classe I/genética , Transfusão de Linfócitos , Polimorfismo Genético , Aborto Habitual/genética , Aborto Habitual/imunologia , Feminino , Frequência do Gene , Predisposição Genética para Doença , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Antígenos HLA-C/genética , Antígenos HLA-DR/genética , Cadeias HLA-DRB1 , Antígenos HLA-G , Haplótipos , Humanos , Nascido Vivo , Seleção de Pacientes , Gravidez , Resultado do TratamentoRESUMO
To investigate the possible association of recurrent spontaneous abortions (RSA) of immune aetiologies with neonatal sex differences, karyotyping of abortuses from allo-immune RSA and epidemiological studies on the sex differences of neonates from sporadic aborters was carried out. Allo-immune disorders, as diagnosed by an increased number of shared HLA class II loci and reduced blocking activity of the woman's serum in mixed lymphocyte reaction, were found almost twice (54.9%) as often as auto-immune disorders (29.9%) among a total of 244 women with RSA. Of 33 abortuses karyotyped from women with RSA, 69.7% showed normal female karyotypes, while only 6.1% had normal male karyotypes, indicating that female fetuses are more prone to abort than males. Epidemiological studies revealed that boys were born at a significantly greater incidence of 58.1% in 221 women with a history of sporadic abortion than 47.6% in 893 women with no history of abortion. Moreover, the proportion of women giving birth to boys only was consistently and significantly higher, regardless of repeated deliveries, in sporadic aborters (36.7%) than in women with no history of abortion (19.6%), showing that more boys were born than girls to women with sporadic abortion. It is concluded that male fetuses are more likely to survive than females in allo-immune RSA due to allo-immune reproductive wastage of chromosomally normal female concept in early human pregnancy, and that allo-immune RSA makes up the highest proportion of unexplained RSA.