Akemi Kuroda Chiba

Allelic polymorphisms of human Fcγ receptor IIa and Fcγ receptor IIIb among distinct groups in Brazil

BACKGROUND: The FcγRIIA gene is expressed in two polymorphic forms, R131 and H131, which differ by the replacement of histidine by arginine at position 131. The FCGR3B (FcγRIIIB) gene exists in two allelic isoforms, known as FCGR3B1 (FcγRIIIB‐NA1) and FCGR3B2 (FcγRIIIB‐NA2), which differ in nucleotides 141, 147, 227, 277, and 349. An additional polymorphism is the SH antigen that is associated with the FCGR3B3 (FcγRIIIB‐SH) allele.

Human neutrophil alloantigens systems

Neutrophil alloantigens are involved in a variety of clinical conditions including immune neutropenias, transfusion-related acute lung injury (TRALI), refractoriness to granulocyte transfusions and febrile transfusion reactions. In the last decade, considerable progress has been made in the characterization of the implicated antigens. Currently, seven antigens are assigned to five human neutrophil antigen (HNA) systems. The HNA-1a, HNA-1b and HNA-1c antigens have been identified as polymorphic forms of the neutrophil Fcgamma receptor IIIb (CD16b), encoded by three alleles. Recently, the primary structure of the HNA-2a antigen was elucidated and the HNA-2a-bearing glycoprotein was identified as a member of the Ly-6/uPAR superfamily, which has been clustered as CD177. The HNA-3a antigen is located on a 70-95 kDa glycoprotein; however, its molecular basis is still unknown. Finally, the HNA-4a and HNA-5a antigens were found to be caused by single nucleotide mutations in the alphaM (CD11b) and alphaL (CD11a) subunits of the leucocyte adhesion molecules (beta2 integrins). Molecular and biochemical characterization of neutrophil antigenshave expanded our diagnostic tools by the introduction of genotyping techniques and immunoassays for antibody identification. Further studies in the field of neutrophil immunology will facilitate the prevention and management of transfusion reactions and immune diseases caused by neutrophil antibodies.

RHD alleles in Brazilian blood donors with weak D or D‐negative phenotypes

The RHD gene is highly polymorphic and the existence of a large number of alleles results in RhD variant phenotypes. RHD genotyping has been used to distinguish normal D antigen from D variants due to limitations of serologic methods. The purpose of this study was to determine the phenotypic frequency of RhD and RhCE antigens and to investigate the RHD alleles present in samples with the weak D or D− phenotypes from Brazilian blood donors. A total of 2007 donors were phenotyped for D, C, c, E and e antigens. Samples phenotyped as D− were genotyped by polymerase chain reaction‐sequence specific primers, and exon 10 and intron 4 of the RHD gene were analysed. D− samples containing the RHD gene or samples considered weak D were further characterised using genotyping platform or nucleotide sequencing. Using serologic methods we found that 87·3% of the donors were D+, 11·9% D− and 0·8% weak D. The frequency of RHD gene in D− individuals was 9·2%. Five RHD alleles from phenotypically D− donors were characterised in six molecular backgrounds: RHDΨ, RHD‐CE‐Ds, RHD‐CE‐(2‐9)‐D, RHD/RHDΨ, RHDΨ/RHD‐CE‐Ds and RHD‐CE(2)‐D. The most common weak D antigens types found were 1, 3, 4·0/4·1 and 4·2, whereas the most prevalent weak D type was 4·2 (or DAR). The RHD genotyping proved to be a necessary tool to characterise RHD alleles in donors phenotyped as D− or weak D to increase the transfusion safety in highly racial mixed population.

Molecular studies reveal that A134T, G156A and G1333A SNPs in the CD177 gene are associated with atypical expression of human neutrophil antigen-2.

Background and Objectives  The human neutrophil antigen‐2 (HNA‐2) is expressed on a subpopulation of neutrophils as most subjects present a negative plus a positive HNA‐2 population of neutrophils. The number of neutrophils expressing HNA‐2 is variable and may increase in pregnancy, infections, myeloproliferative disorders and after G‐CSF. This study investigated the presence of polymorphisms in the gene encoding HNA‐2 (CD177) in individuals presenting different patterns of antigen expression and determined the association of single nucleotide polymorphisms (SNPs) with the heterogeneous HNA‐2 expression.

Gene frequencies of the HPA‐15 (Gov) platelet alloantigen system in Brazilians

Summary.  The HPA‐15 (Gov) alloantigen is a biallelic co‐dominant system on human platelets, and its allele HPA‐15a and HPA‐15b differ by an A→C single nucleotide polymorphism at nucleotide 2108 of the coding sequence resulting in a Tyr682Ser substitution in the mature CD109 glycoprotein.

A very strict guideline reduces the number of erythrocyte transfusions in preterm infants.

Background and Objectives  Benefits of adopting restrictive guidelines for erythrocyte transfusions are still controversial. The objective of this study was to verify if a very strict guideline could reduce erythrocyte transfusions in preterm infants without adverse outcomes.

Impact of using different laboratory assays to detect human leukocyte antigen antibodies in female blood donors

BACKGROUND: HLA antibodies passively transferred to transfused recipients may cause transfusion reactions such as transfusion‐related acute lung injury (TRALI), but in many of the reported TRALI incidents, no white blood cell antibodies have been identified. We investigated whether a higher number of anti‐HLA would be detected in donors plasma by using a method with potential higher sensitivity rate.

Gene frequencies of the HNA‐4a and ‐5a neutrophil antigens in Brazilian persons and a new polymerase chain reaction‐restriction fragment length polymorphism method for HNA‐5a genotyping

BACKGROUND: The HNA‐4a (Mart) and HNA‐5a (Ond) antigens are polymorphic variants of αM (CD11b) and αL (CD11a) subunits of the β2‐integrin, and are associated with single nucleotide polymorphisms (SNP) leading to amino acid dimorphisms. HNA‐4a has been linked to alloimmune neonatal neutropenia, but the HNA‐5a clinical significance is unclear.

RBC-associated IgG in patients with visceral leishmaniasis (kala-azar): a prospective analysis.

BACKGROUND: Despite the fact that anemia is one of the most striking clinical features of visceral leishmaniasis (kala‐azar), the factors involved in its pathogenesis are not fully understood. Although the cause of the anemia seen in these patients is often multifactorial, sequestration and destruction of the RBCs in the enlarged spleen, immune mechanisms, and alterations in RBC membrane permeability have been implicated.

HNA-3 gene frequencies in Brazilians and a new polymerase chain reaction-restriction fragment length polymorphism method for HNA-3a/3b genotyping

HNA‐3 antigens are the result of a rs2288904 single‐nucleotide polymorphism (SNP) in the CTL2, and the HNA‐3a and HNA‐3b variants are encoded by a guanine and adenine at Nucleotide Position 461. Anti‐HNA‐3 are involved in severe transfusion‐related acute lung injury reactions and in neonatal alloimmune neutropenia. Since the distribution of the HNA‐3 system was unknown in South Americans, in this study we determined the frequency of the HNA‐3 alleles in Brazilians.