RESUMO
BACKGROUND: Merozoites of Plasmodium falciparum invade through several pathways using different RBC receptors. Field isolates appear to use a greater variability of these receptors than laboratory isolates. Brazilian field isolates were shown to mostly utilize glycophorin A-independent invasion pathways via glycophorin B (GPB) and/or other receptors. The Brazilian population exhibits extensive polymorphism in blood group antigens, however, no studies have been done to relate the prevalence of the antigens that function as receptors for P. falciparum and the ability of the parasite to invade. Our study aimed to establish whether variation in the GYPB*S/s alleles influences susceptibility to infection with P. falciparum in the admixed population of Brazil. METHODS: Two groups of Brazilian Amazonians from Porto Velho were studied: P. falciparum infected individuals (cases); and uninfected individuals who were born and/or have lived in the same endemic region for over ten years, were exposed to infection but have not had malaria over the study period (controls). The GPB Ss phenotype and GYPB*S/s alleles were determined by standard methods. Sixty two Ancestry Informative Markers were genotyped on each individual to estimate admixture and control its potential effect on the association between frequency of GYPB*S and malaria infection. RESULTS: GYPB*S is associated with host susceptibility to infection with P. falciparum; GYPB*S/GYPB*S and GYPB*S/GYPB*s were significantly more prevalent in the in the P. falciparum infected individuals than in the controls (69.87% vs. 49.75%; P<0.02). Moreover, population genetics tests applied on the GYPB exon sequencing data suggest that natural selection shaped the observed pattern of nucleotide diversity. CONCLUSION: Epidemiological and evolutionary approaches suggest an important role for the GPB receptor in RBC invasion by P. falciparum in Brazilian Amazons. Moreover, an increased susceptibility to infection by this parasite is associated with the GPB S+ variant in this population.
Assuntos
Predisposição Genética para Doença/genética , Genética Populacional , Glicoforinas/genética , Malária Falciparum/genética , Plasmodium falciparum/fisiologia , Polimorfismo Genético/genética , Alelos , Brasil/epidemiologia , Estudos de Casos e Controles , Doenças Endêmicas , Frequência do Gene , Marcadores Genéticos , Humanos , Malária Falciparum/epidemiologiaRESUMO
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
BACKGROUND: The Cromer blood group system consists of seven high-incidence and three low-incidence antigens carried on decay-accelerating factor (DAF). This report describes the identification and characterization of a new Cromer high-incidence antigen, named GUTI. STUDY DESIGN AND METHODS: RT-PCR and sequence analysis were performed on cDNA prepared from a Chilean donor whose serum contained the alloantibody (anti-GUTI). Based on the observed point mutation, a PCR-RFLP assay using MaeII was developed. To map the epitope, DAF-deletion mutants were tested by immunoblotting with anti-GUTI. RESULTS: Sequence analysis revealed a substitution of 719G>A in DAF in the proband. The proband's parents and two daughters were heterozygotes for 719G>A, one sister whose RBCs typed GUTI- was homozygous for 719A, and one sister had the wild-type DAF (719G). Seven additional heterozygote samples were identified among 214 Chileans. No heterozygotes were found in 197 New York donors. Analysis using DAF-deletion mutants showed the antigenic determinant to be within short consensus repeat (SCR) 4. CONCLUSION: This study describes a novel high- incidence antigen (GUTI) in the Cromer blood group system characterized by the amino acid arginine at position 206 in SCR4 of DAF. The GUTI-negative proband has a substitution mutation that predicts for histidine at this position.
Assuntos
Antígenos de Grupos Sanguíneos/imunologia , Antígenos CD55/imunologia , Isoantígenos/genética , Adulto , Chile , DNA Complementar/química , Desoxirribonucleases de Sítio Específico do Tipo II , Membrana Eritrocítica/química , Membrana Eritrocítica/imunologia , Deleção de Genes , Humanos , Isoanticorpos/sangue , Isoantígenos/química , Isoantígenos/imunologia , Masculino , Mutação , Polimorfismo de Fragmento de Restrição , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de DNARESUMO
In this report the blood groups, about 25 accepted by the International Society for Blood Transfusion, are described along with their function and importante in transfusion medicine.
No relato são descritos os grupos sanguíneos, cerca de 25 relatados e aceitos pela Sociedade Internacional de Transfusão de Sangue, sua função e importância na medicina transfusional.
Assuntos
Sistema ABO de Grupos SanguíneosRESUMO
The importance and the use of synthetic peptides and recombinant proteins in immunohematology and the identification of antibodies are presented and discussed in this report.
No relato é apresentada e discutida a importância e o emprego dos peptideos sintéticos a proteinas recombinantes em imunohematologia e identificação de anticorpos.