Neutrophil counts in persons of African origin

ArticleinCurrent opinion in hematology 21(1) · November 2013with120 Reads
DOI: 10.1097/MOH.0000000000000007 · Source: PubMed
Abstract
The causes of ethnic or benign neutropenia have long been unclear. Here, we discuss the emerging data on the causes and consequences of neutropenia and discuss the relevance of these data for African populations, in which the prevalence of neutropenia is high. Genetic deletion of the Duffy antigen receptor for chemokines (DARC-null genotype) has been identified as a major determinant for neutropenia. DARC acts as a receptor for Plasmodium vivax malaria and the DARC-null genotype has thus been positively selected among Africans; however, recent studies suggest that Duffy-null-linked neutropenia could increase the risk of HIV infection. Data are emerging that neutrophils are versatile cells that play a critical role not only in direct antimicrobial activity but also in priming and regulating the activity of other innate and adaptive immune cells. Therefore, we discuss here the imperative to better understand the causes, consequences, and the underlying mechanisms of neutropenia among Africans as a prerequisite for rational and optimal biomedical interventions to improve health outcomes. Neutropenia among Africans, linked to the Duffy-null trait or otherwise, may have significant health consequences that remain largely undetermined and could have a significant impact on the pathogenesis of diseases.
    • "This unchanged frequency, over an estimated18-year-period, is an epidemiological evidence of its benign nature. The positive correlation between the monocyte and neutrophil counts in four large ethnic groups (Egyptians, Sudanese, Emiratis and Indians) supports benign rather than secondary NP, in which monocytosis is a more common finding [30][31][32]. In general, our findings agree with earlier reports of a high frequency of benign NP in children from Sudan and Jordan [4, 6]. "
    [Show abstract] [Hide abstract] ABSTRACT: Background: A high prevalence of neutropenia has been reported in several ethnic groups amongst whom many healthy individuals with low neutrophil counts undergo unnecessary investigations. This study aims to ascertain the prevalence of neutropenia (NP) in a large cohort of children from North African, Middle Eastern, and Asian countries residing in the United Arab Emirates. Methods: Neutrophil counts of 26,542 children (one day to six years of age) from 86 countries were analyzed. The subjects were enrolled in the Well-Child-Care program of Ambulatory Health Services of Emirate of Abu Dhabi, United Arab Emirates. NP was defined as a neutrophil count <1.5 × 10(9)/L and severe NP <0.5 × 10(9)/L. Results: The neutrophil counts reached a nadir in the fourth week of life and changed slightly from the age of six-months to six-years. The frequency of NP was (from West-to-East): North African Arabs 15.4 %, Green Crescent Arabs 9.8 %, Peninsular Arabs 10.9 %, Iranians 3.1 %, Afghanis 2.5 %, Pakistanis 5.6 %, Indians 10.2 %, and Filipinos 7.3 %. The frequency of severe NP in North African Arabs (Sudanese) was 2.8 %, Green Crescent and Peninsular Arabs ≤1 %, Indians 1.5 %, and Filipinos 1.8 %. In 12,703 Emirati children, the frequency of NP was 10.6 % similar to their adult counterparts. Conclusion: The prevalence of childhood NP varied considerably by geoethnicity. Measures to prevent the inappropriate investigations of healthy children with benign neutropenia are proposed.
    Full-text · Article · Dec 2016
    • "But for the Botswana population, the ABO groups do not appear to have any role in enhancing or diminishing HIV risk of infection. We did not find any risks associated with the Duffy blood group system or its Duffy-null phenotype alluded to elsewhere [17, 21, 22, 36]. Our results in this respect appear to support an insignificant role of Duffy blood group expression consistent with other investigators[20, 37]. "
    [Show abstract] [Hide abstract] ABSTRACT: Background: Botswana is among the world's countries with the highest rates of HIV infection. It is not known whether or not this susceptibility to infection is due to genetic factors in the population. Accumulating evidence, however, points to the role of erythrocytes as potential mediators of infection. We therefore sought to establish the role, if any, of some erythrocyte antigens in HIV infection in a cross-section of the population. Methods: 348 (346 HIV-negative and 2 HIV-positive) samples were obtained from the National Blood Transfusion Service as residual samples, while 194 HIV-positive samples were obtained from the Botswana-Harvard HIV Reference Laboratory. Samples were grouped for twenty three antigens. Chi-square or Fischer Exact analyses were used to compare the frequencies of the antigens in the two groups. A stepwise, binary logistic regression was used to study the interaction of the various antigens in the light of HIV-status. Results: The Rh antigens C and E were associated with HIV-negative status, while blood group Jka, P1 and Lub were associated with HIV-positive status. A stepwise binary logistic regression analysis yielded group C as the most significant protective blood group while Lub and P1 were associated with significantly higher odds ratio in favor of HIV-infection. The lower-risk-associated group C was significantly lower in Africans compared to published data for Caucasians and might partially explain the difference in susceptibility to HIV-1. Conclusion: The most influential antigen C, which also appears to be protective, is significantly lower in Africans than published data for Caucasians or Asians. On the other hand, there appear to be multiple antigens associated with increased risk that may override the protective role of C. A study of the distribution of these antigens in other populations may shed light on their roles in the HIV pandemic.
    Full-text · Article · Feb 2016
    • "However, there is clinical evidence of complexities in the Duffy blood group beyond what has been previously described. Specifically, we observe complexity beyond the two major DARC alleles in presentations of varied clinical manifestations linked to DARC including, neutropenia [23, 24], organ system damage in sickle cell disease[25] , cancer metastasis regulation[26] as well as hemolytic complications arising from immunological responses among Duffy antigens during blood transfusions [27]. At least in part, these observations could be explained by considering the alternative protein isoforms which would increase the repertoire of antigens 2-fold. "
    [Show abstract] [Hide abstract] ABSTRACT: The Atypical ChemoKine Receptor 1 (ACKR1) gene, better known as Duffy Antigen Receptor for Chemokines (DARC or Duffy), is responsible for the Duffy Blood Group and plays a major role in regulating the circulating homeostatic levels of pro-inflammatory chemokines. Previous studies have shown that one common variant, the Duffy Null (Fy-) allele that is specific to African Ancestry groups, completely removes expression of the gene on erythrocytes; however, these individuals retain endothelial expression. Additional alleles are associated with a myriad of clinical outcomes related to immune responses and inflammation. In addition to allele variants, there are two distinct transcript isoforms of DARC which are expressed from separate promoters, and very little is known about the distinct transcriptional regulation or the distinct functionality of these protein isoforms. Our objective was to determine if the African specific Fy- allele alters the expression pattern of DARC isoforms and therefore could potentially result in a unique signature of the gene products, commonly referred to as antigens. Our work is the first to establish that there is expression of DARC on lymphoblasts. Our data indicates that people of African ancestry have distinct relative levels of DARC isoforms expressed in these cells. We conclude that the expression of both isoforms in combination with alternate alleles yields multiple Duffy antigens in ancestry groups, depending upon the haplotypes across the gene. Importantly, we hypothesize that DARC isoform expression patterns will translate into ancestry-specific inflammatory responses that are correlated with the axis of pro-inflammatory chemokine levels and distinct isoform-specific interactions with these chemokines. Ultimately, this work will increase knowledge of biological mechanisms underlying disparate clinical outcomes of inflammatory-related diseases among ethnic and geographic ancestry groups.
    Full-text · Article · Oct 2015
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