RESUMEN
HLA-G is a non-classical human leukocyte antigen expressed primarily in fetal tissues at the maternal-fetal interface. This expression pattern is unique among HLA genes and suggests that HLA-G may be involved in interactions that are critical in establishing and/or maintaining pregnancy. To evaluate the role of polymorphisms at this locus in maternal-fetal interactions, 113 couples with unexplained recurrent miscarriage were genotyped for seven polymorphisms that define 12 HLA-G alleles. Logistic regression analysis was used to assess whether HLA-G genotypes were associated with an increased risk for a subsequent miscarriage. The presence of an HLA-G*0104 or HLA-G*0105N allele in either partner was significantly associated with an increased risk for miscarriage, after adjustment for maternal age, number of previous miscarriages, history of a previous liveborn, and treatment with paternal mononuclear cells. The *0104 and *0105N alleles are defined by polymorphisms in the alpha-2 domain and encode protein variants that are present only in the full-length HLA-G1 protein. The significant genotype-specific risk in this population suggests that allelic variation in the alpha-2 domain of the HLA-G1 isoforms contributes to recurrent miscarriage.
Asunto(s)
Aborto Habitual/genética , Antígenos HLA/genética , Antígenos de Histocompatibilidad Clase I/genética , Polimorfismo Genético , Embarazo , Aborto Habitual/inmunología , Adulto , Alelos , Femenino , Genotipo , Antígenos HLA/inmunología , Antígenos HLA/metabolismo , Antígenos HLA-G , Antígenos de Histocompatibilidad Clase I/inmunología , Antígenos de Histocompatibilidad Clase I/metabolismo , Humanos , Masculino , Resultado del Embarazo , Factores de Riesgo , Resultado del TratamientoRESUMEN
HLA-G is a non-classical class Ib gene with many unusual features. Because of its unique expression pattern, which is primarily limited to fetal cells at the maternal fetal interface, this gene has gained the attention of many investigators. In this paper we review some of the novel features of HLA-G, with particular reference to polymorphic variants in the gene, and discuss the implications of these features for the potential function and evolutionary history of HLA-G.
Asunto(s)
Evolución Molecular , Antígenos HLA/genética , Antígenos de Histocompatibilidad Clase I/genética , Polimorfismo Genético , Alelos , Empalme Alternativo , Secuencia de Bases , Codón/genética , Femenino , Feto/inmunología , Genes MHC Clase I , Antígenos HLA/química , Antígenos HLA/fisiología , Antígenos HLA-A/genética , Antígenos HLA-G , Antígenos de Histocompatibilidad Clase I/química , Antígenos de Histocompatibilidad Clase I/fisiología , Humanos , Desequilibrio de Ligamiento , Modelos Moleculares , Mutación , Embarazo , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
Molecular typing of HLA class II loci has been performed on a sample of 196 patients with Hodgkin lymphoma. Division of patients into two histological categories--nodular sclerosing Hodgkin disease versus all other types--shows significant overall association of the nodular sclerosing group with the HLA class II region. Haplotypes and alleles defined for the four loci typed--DRB1, DQA1, DQB1, and DPB1--were present in both excess and deficit in the nodular sclerosing sample. Some of the effects are attributable to particular DRB1 and DQB1 alleles, while other effects are best explained by haplotypes marking the entire class II region. The latter effects might be due to variation in additional, as-yet-unexamined loci in the class II region or to particular combinations of alleles from two or more loci. These data also explain why earlier studies showed HLA linkage but not association, and they substantiate the specific involvement of the immune system in certain neoplastic diseases.