Elyse Moritz

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.

Antibodies to human neutrophil antigen HNA-3b implicated in cases of neonatal alloimmune neutropenia: ANTI-HNA-3B IMPLICATED IN CASES OF NAIN

Neonatal alloimmune neutropenia results from maternal alloimmunization to human neutrophil antigens. The alloantibodies involved in neonatal alloimmune neutropenia are against human neutrophil antigens HNA‐1a, HNA‐1b, HNA‐1c, HNA‐1d, HNA‐2, HNA‐3a, HNA‐4a, HNA‐4b, and HNA‐5a; however, to date, antibodies specific to HNA‐3b have not been reported.

Distribution of HNA alleles in Brazilians

Dear Editor, The manuscript ‘Neutrophil alloantigens and alloantibodies in different populations’ [1] brings important updates on the subject and conducts a comprehensive review of the allelic frequencies of HNAs, especially in the Asian population. However, in terms of the Brazilian population, some changes should be considered, since the reported HNA frequencies are only representative of isolated native indigenous groups in which inbreeding (endogamy) prevails. We consider that the HNA frequencies that best represent the totality of the Brazilian population are observed in studies including blood donors, which reflect more adequately the high miscegenation rate of our population. In fact, the distribution of HNA alleles in indigenous groups is remarkably different from that reported for blood donors, who have a profile similar to Europeans. In this context, the data from studies involving Brazilian blood donors are compiled in Table 1, expressing more accurately the frequencies of the HNA alleles in Brazilians. Conflict of interests