RESUMO
Progress in transplantation has relied on similar human leukocyte antigen (HLA) matching between the donor and the patient, while the role of other immunologic factors like non-HLA markers including minor histocompatibility antigens (miHA) are currently in the forefront. miHA are polymorphic proteins that vary even in monozygotic twins. The best known is the H-Y antigen, but there are also other autosomal miHA and MICA (MHC class I chain-related gene A). miHA have been well studied in transplantation of hematopoietic precursors, but not in solid organ transplantation. The most important studies in this field relate to incompatibility of H-Y antigen as a risk factor in kidney transplantation, although the findings are still inconclusive. This review presents the role of minor histocompatibility antigens in solid organ transplantation, especially of the kidney.
Assuntos
Transplante de Rim/métodos , Antígenos de Histocompatibilidade Menor/imunologia , Animais , Rejeição de Enxerto , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/imunologia , Antígeno H-Y/imunologia , Histocompatibilidade/imunologia , Antígenos de Histocompatibilidade Classe I/metabolismo , Teste de Histocompatibilidade , Humanos , Camundongos , Antígenos de Histocompatibilidade Menor/metabolismo , Prognóstico , Insuficiência Renal Crônica/terapia , Fatores de Risco , Resultado do TratamentoRESUMO
BACKGROUND: The Dombrock (Do) blood group system consists of six distinct antigens: Do(a) , Do(b) , Gy(a) , Hy, Jo(a) , and DOYA. Our finding of a pregnant patient whose red blood cells (RBCs) were Hy+ but whose serum contained an apparent alloanti-Hy suggested the presence of a seventh antigen and prompted this study. STUDY DESIGN AND METHODS: Standard hemagglutination and polymerase chain reaction-based methods were used throughout. RESULTS: The patient's RBCs typed as Do(a-b+(w) ), Gy(a+(w) ), Hy+(w) , Jo(a+(w) ), and DOYA+(w) . Her serum agglutinated RBCs with common Dombrock phenotypes. Hy- RBC samples were very weakly reactive or nonreactive, Jo(a-) and DOYA- RBC samples were reactive, and Gy(a-) RBC samples were nonreactive. Reactivity was obtained with RBCs treated with papain or α-chymotrypsin, but not with RBCs treated with trypsin or dithiothreitol. DNA analysis showed the patient to be DO*793G (DO*B/DO*B), DO*323G, DO*350C, DO*547T, and DO*898G and revealed two homozygous nucleotide changes of DO*431C>A and DO*432C>A in Exon 2, which predicts a change of Ala (GCC) at Amino Acid 144 to Glu (GAA). This indicates that she is homozygous DO*B-WL with Nucleotide 431 and 432 changes, which without knowing the effect of the two novel changes, is predicted to encode the Do(a-b+), Gy(a+), Hy+, Jo(a+), DOYA+ phenotype. CONCLUSIONS: The antibody in the patient's plasma recognizes the high-prevalence antigen absent from her RBCs. The Ala144Glu change caused an absence of a high-prevalence Do antigen that we have named DOMR [provisional ISBT number 014007 (DO7)]. The absence of DOMR is associated with weakening of Do(b) , Gy(a) , Hy, Jo(a) , and DOYA antigens.
Assuntos
Antígenos de Grupos Sanguíneos/imunologia , Antígeno H-Y/imunologia , Antígenos de Grupos Sanguíneos/genética , Eritrócitos/imunologia , Feminino , Hemaglutinação , Humanos , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , GravidezRESUMO
A child with ambiguous genitalia was born after an uncomplicated pregnancy. Laparotomy revealed intraabdominal hypoplastic testes containing normal appearing Leydig cells; germ cells were present in the left gonad, not in the right. The karyotype was 46,XY in blood leukocytes and in fibroblasts cultured from the gonads; there was no evidence of mosaicism. Endocrinologic study revealed no disorder of steroidogenesis. Androgen receptors were not studied. Serologic evaluation of blood leukocytes revealed the presence of H-Y antigen, but there are reasons to believe that less H-Y antigen was present in the cells of the patient than was present in corresponding cells from normal males. Gonadectomy and clitoral recession were performed at 3 weeks of age, and the patient was reared as a girl. We speculate that reduced expression of H-Y may have induced aberrant development of the gonads.