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ABSTRACT Background: The atypical chemokine receptor 1 (ACKR1) gene encodes the Duffy blood group antigens in two allelic forms: FY*A (FY*01) and FY*B (FY*02), which define the Fy(a+b-), Fy(a-b+), and Fy(a+b+) phenotypes. FY*BES (FY*02N.01) is a single T to C substitution at nucleotide -67 that prevents the FY*B from being expressed in red blood cells (RBCs). Methods: We evaluated 250 residents from a Brazilian malarial endemic region (RsMR). All individuals were phenotyped for Fya and Fyb antigens and genotyped for FY*A, FY*B, FY*B SE , and FY*B weak alleles. Results: Among the 250 individuals, 209 (83.6%) reported previous malaria infection, and 41 (16.4%) did not. The Fy(a+b+) phenotype was present in 97/250 (38.8%), while the Fy(a-b-) was present in 7/250 (2.8%). The FY*A/FY*B was found in 130/250 (52%) and the FY*A/FY*A in 45/250 (18%). The c.1-67>TC was present, in homozygosity, in 11/250 (4.4%). Among 34 individuals with the Fy(a+b-) and FYA*/FYB* mutations, 4/34 (11.8%) had homozygosity for the c.1-67T>C. One individual presented the Fy(a+b-), FY*A/FY*B, and c.1-67T>C in homozygosis, whereas the other presented the Fy(a+b-), FY*A/FY*A, and c.1-67T>C in heterozygosis. Conclusions: We reported a low prevalence of the Fy(a-b-) in persons who had previously been infected with Plasmodium vivax (67.5%). We observed that 102/141 (72.3%) individuals expressing the Fyb antigen had a P. vivax infection, indicating the importance of the Fyb antigen, silenced by a c.1-67T>C mutation in homozygosis, in preventing the P. vivax infection. We showed that the c.1-67T>C mutation in the FY*A did not silence the FY*A expression on RBCs.

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Duffy blood group phenotypes [Fy(a + b-), Fy(a-b+), Fy(a + b+), Fy(a-b-)], characterized by the expression of Fya, and Fyb antigens, are present in red blood cells. Therefore, we hypothesize that the non-hematopoietic expression of these antigens might influence cell invasion by T. gondii. 576 consecutive patients from both genders were enrolled. The presumed OT clinical diagnosis was performed. Duffy phenotyping was performed by hemagglutination in gel columns and for the correct molecular characterization Fy(a-b-) phenotype, using PCR-RFLP. Anti-T. gondii IgG antibodies were detected by ELISA. Chi-square, Fisher's exact tests were used to compare the proportions. OT was present in 22.9% (n = 132) and absent in 77.1% (n = 444) of patients. The frequencies of anti-T. gondii IgG antibodies were higher in OT (127/132, 96.2%) than those without this disease (321/444, 72.3%) (p < .0001). None of the Duffy antigens or phenotypes were associated with T. gondii infection (χ2: 2.222, GL: 3, p = .5276) as well as the risk of OT (χ2: 0.771, GL: 3, p = .8566). Duffy blood group system phenotypes and their antigens do not constitute risk factors for infection by T. gondii infection and the development of OT.

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The atypical chemokine receptor 1 gene (ACKR1) is responsible for the clinically significant Duffy blood group. The main antigens of this system, Fya and Fyb, can be related to a null or weak expression of the DARC protein. In the present work, we aimed to identify ACKR1 gene variants in blood donors from southern Brazil based on discrepancies between their serological and molecular typing results. Then, we analyzed the association of these variants with the expression of the Duffy phenotype. The Fy antigen types were determined via hemagglutination and real-time PCR (c.125 G > A, c.265C > T and c.-67T > C SNPs) tests in a sample composed of 382 regular repetitive voluntary blood donors to the Blood Bank of Hospital de Clínicas de Porto Alegre. An inconclusive correlation between phenotype-genotype analyses was found in 11 (2.88 %) donors, and the entire ACKR1 gene was sequenced in these samples. Our investigation found 11 genetic variants, four of which (c.-541C > T, c.21 + 150C > T, c.22-58A > G, and c.298 G > A SNPs) seem to have putative functional effects on the structure and expression of DARC undertaken for in silico analysis (SIFT, PolyPhen-2 and RegulomeDB). Molecular events can result in apparent discrepancies between red cell genotypes and phenotypes. Our findings provided insight into the molecular background of FY antigens to improve technical approaches for red cell genotyping.

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In regions with an Afro-descendant population and where malaria is endemic, high frequencies of polymorphisms have been found that confer resistance to this disease, such as the haemoglobin S (HbS) and Duffy genes, which provide resistance to P. falciparum and P. vivax infection, respectively. The objective of this study was to evaluate the individual and joint selection actions of these two genes in an Afro-descendant Colombian population. A total of 819 individuals were analysed using stratified random sampling. PCR-RFLP and Hardy-Weinberg equilibrium deviation analysis (H-W eq.), linkage disequilibrium (LD), D'IS2 and D'ST2 indexes, neutrality tests, correlations and fitness were performed using Arlequin 3.5.2.2 and R 3.4.1 software. In general, the population showed neutrality and H-W eq. for the HbS gene but not for the Duffy gene (FYA/FYB, FYA/FYBES and FYB/FYBES genotypes were responsible for this deviation). LD between the HbS locus and the promoter region of the Duffy gene, a value D'IS2 = 0.001 and D'ST2 = 0.020 was found, an increase in fitness of the AS*FYBES/FYBES genotype combination (marked in adolescents and adults), and a strong correlation between these genotypes (Rho = 90%, p = .001) were found, evidencing a possible joint selection action for these two alleles. This work presents evidence of the action of natural selection, both individually and jointly, on malaria resistance genes, HbS and Duffy, in the Buenaventura population.

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Sickle cell anemia was a rare disease in Chile, especially in adults, however the recent immigration wave from Haiti is changing this scenario. We report a 29 year old black female from Haiti with a non-disclosed history of sickle cell anemia. She was transfused with two units of red blood cells, found unconscious and with jaundice five days later and admitted to the hospital. On admission she had a hemoglobin of 3.3 g/dL, a total bilirubin of 5.08 mg/dL, a LDH of 1,306 Ui/L. She was transfused again, worsening her condition. An alloimmunization and delayed hemolytic reaction was suspected. A direct Coombs test was positive. She was treated with steroids and her serum hemoglobin rose progressively.

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Malaria is an endemic disease in a large part of Colombia, and the city of Buenaventura reports one of the highest malaria infection rates. Some genetic variants confer resistance to malaria, such as the heterozygote for hemoglobin S (HbS) and the homozygous variant FYBES/FYBES of the Duffy gene. The aim of this work was the molecular characterization of these genes in an Afrodescendant population from the urban area of Buenaventura. A total of 819 individuals from a stratified random sampling in each of the 12 communities of this city were analyzed. Molecular analysis was performed using PCR-RFLP, and data analysis was performed using Arlequin 3.5, SPSS 20.0, and R 3.4.1. Frequencies of 3.1% and 72.2% were obtained for the S and FYBES alleles, respectively, with 6.1% AS heterozygous and 55% FYBES/FYBES homozygous genotypes. The highest percentages of the resistant genotype (genotypic combination AA*FYBES/FYBES) were found for the 13-27-year age group (8.2%) and communities 1 and 3 (18% and 10.3%, respectively). Therefore, it would be pertinent to consider the remaining communities and age groups when performing epidemiological studies and preventive and health care campaigns on malaria in the urban areas of the city of Buenaventura.

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Duffy blood group system is of interest in several fields of science including transfusion medicine, immunology and malariology. Although some methods have been developed for Duffy polymorphism genotyping, not all of them have been sufficiently described and validated, and all present limitations. At the same time, the frequency of Duffy alleles and antigens in some densely populated regions of the world are still missing. In this study we present new tests for genotyping the major alleles of the Duffy blood system and describe Duffy alleles and antigens in blood donors and transfusion-dependent patients in Minas Gerais, Brazil. A simple and reproducible strategy was devised for Duffy genotyping based on real-time PCR that included SNPs rs12075 and rs2814778. No significant differences between the allele frequencies were observed comparing blood donors and patients. Among the blood donors, the phenotype Fy(a-b+) was the most common and the Fy(a-b-) phenotype, associated with populations of African descent, was remarkably less common among subjects who self-identified as black in comparison to other ethnoracial categories. However, the African ancestry estimated by molecular markers was significantly higher in individuals with the allele associated to the Duffy null phenotype. The genotyping method presented may be useful to study Duffy genotypes accurately in different contexts and populations. The results suggest a reduced risk of alloimmunization for Duffy antigens and increased susceptibility for malaria in Minas Gerais, considering the high frequency of Duffy-positive individuals.

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La preeclampsia (PE) es una complicación del embarazo que trae consigo algunas consecuencias negativas para la madre y el feto: en la madre provoca principalmente hipertensión y proteinuria, mientras que en el feto puede presentarse trombocitopenia, alteración en el desarrollo del sistema nervioso central y circulatorio, y restricción del crecimiento intrauterino, lo cual se considera el factor de riesgo principal de muerte fetal en nacimientos producto de una PE severa. En la preeclampsia se presenta una disfunción endotelial relacionada con placentación anormal, estado de estrés oxidativo y proceso inflamatorio sistémico, que lleva a la activación de neutrófilos y monocitos. Se ha considerado a la interleucina-8 (IL-8) como un posible candidato desencadenante por ser quimioatrayente y activador de leucocitos; en la circulación sanguínea, la IL-8 se une a un receptor de quimiocina multiespecífico de alta afinidad denominado DARC, que es idéntico al antígeno del grupo sanguíneo Duffy. Este receptor regula los niveles plasmáticos de IL-8, uniéndose a esta quimiocina, pero cuando hay una mutación en la región promotora del gen se altera la expresión de DARC, lo que conlleva a que la IL-8 de los factores genéticos involucrados en la activación de los neutrófilos y de los monocitos, y por ende, en la disfunción endotelial presentada durante este síndrome hipertensivo, especialmente en la población afrodescendiente.

Preeclampsia (PE) is a complication of pregnancy that brings some negative consequences for both mother and fetus. It specially causes hypertension and proteinuria in mothers; while in fetuses it causes thrombocytopenia, development alterations of the central nervous and circulatory system; also intrauterine growth restriction may occur. This last factor is regarded as the main risk factor for fetal death in births as a result of severe PE. There is endothelial dysfunction in preeclampsia related to abnormal placentation, state of oxidative stress and systemic inflammatory process that leads to the activation of neutrophils and monocytes. Interleukin-8 (IL-8) is considered as a possible trigger candidate, since this chemokine is a chemoattractant and leukocyte activator. In the bloodstream, interleukin-8 binds to a high affinity multispecific-chemokine receptor called DARC, which is identical to the Duffy blood group antigen. This receptor regulates plasma levels of IL-8 by binding to chemokine. But, when there is a mutation in the gene promoter region, DARC expression is altered, and IL-8 inefficiently binds to receptor. This mutation results in Duffy negative phenotype, which is present in most of African descendants. This literature review is intended to address the role of IL-8 as neutrophil chemo-attractant, the importance of Duffy blood system and the possible association between ethnicity and preeclampsia.

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Objective: Determine the activity of cortisol in rats treated with exogenous adrenocorticotropic hormone (ACTH) and a resveratrol supplement. Methodology:Forty-eight adult male rats and 16 adult female rats (Rattus norvegicus) three months old with a body weight of 200 to 250g and 300 to 350g for both male and female were used and kept in controlled environmental conditions, temperature of 20±2°C and light-dark cycles of 14 and 10 hours. They were fed with balanced food and had free access to water. The rats were randomly divided into four groups: group 1, was treated with 5 µg/kg of ACTH i.p. every twelve hours; group 2, received the same treatment with ACTH plus a grape extract supplementation of 40 mg/kg; group 3, only received grape extract and group 4,served as control and only received saline solution (0.9%) i.p. The experimental was designed as a 2×2 factorial with two ACTH levels and two extract grape levels. Results:Significant differences were not found in cortisol concentrations for day, gender or treatment effects (0.75ug/dL ± 0.11; p<0.001).

Objetivo: Determinar la actividad de cortisol en ratas tratadas con hormona adrecorticotropa (ACTH) exógena y un suplemento de resveratrol.Metodología:Se utilizaron 48 ratas hembras adultas y 16machos de la cepa wistar (Rattus norvegicus) de tres meses de edad y con un peso corporal de 200-250g y 300-350 g, para hembras y machos, respectivamente, que permanecieron en condiciones ambientales controladas, temperatura 20±2°C de ciclos de luz-oscuridad de 14 y 10 horas, respectivamente.Se les proporcionó alimento balanceado con libre acceso a agua. Las ratas fueron divididas en cuatro grupos al azarasí: grupo 1, fue tratado con 5 µg/kg de ACTH i.p. cada 12 horas; grupo 2, recibió el mismo tratamiento con ACTH además de una suplementación oral de 40 mg/kg de extracto deshidratado de uva (resveratrol); grupo 3, solo recibió extracto de uva y el grupo 4,recibió solución salina y sirvió como control y (0,9%) i.p. y oral. El diseño experimental fue en factorial 2×2, con dos niveles de ACTH y dos niveles de polifenol. Resultados: No se encontraron diferencias significativas del cortisol sanguíneo, con respecto al día y sexo, entre los tratamientos (0,75ug/dL ± 0,11; p<0,001). Conclusión: Los resultados sugieren que el estrés crónico y el consumo de resveratrol no alteran directamente los niveles plasmáticos de cortisol, en ratas estresadas y no estresadas. De la misma manera que, posiblemente la dosis utilizada de ACTH no produjo estimulación de la glándula suprarrenal en las ratas.

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INTRODUCTION: The negative homozygous condition for the Duffy blood group (Fy-/Fy-) confers natural resistance to Plasmodium vivax infection. Studies carried out in pursuing this direction in Colombia are scarce. OBJECTIVE: To describe the relationship between Duffy genotypes in three ethnic communities of La Italia (Chocó) and malarial infection. METHODS: This is a descriptive, cross-sectional study in symptomatic and asymptomatic subjects with malaria. SAMPLE SIZE: Afro-Colombians 73; Amerindian (Emberá) 74, and Mestizo, 171. The presence of Plasmodium infection was assessed by thick smear and the status of the Duffy gene was studied by PCR and RFLP to help identify changes to T-46C and A131G which originate the genotypes T/T, T/C , C/C and G/G, G/A, A/A. RESULTS: Infection by Plasmodium was detected in 17% of cases with 62% due to P. falciparum and 27% due to P. vivax. Duffy genotypes were significantly associated with ethnicity (p= 0.003). Individuals with the C/C, A/A diplotypes were exclusively infected by P. falciparum, whereas the other diplotypes were infected with either of the species. In the Amerindian and Mestizo populations, the frequency of the T-46 allele was 0.90-1.00, among Afro-Colombians this was 0.50, the same as with the C allele and with an absence of heterozygous. At locus 131, the maximum frequency of the G allele was 0.30 in Amerindians and the maximum of the A allele was 0.69 in Afro-Colombians. CONCLUSIONS: In the Amerindian and mestizo populations studied, there was a predominance of the allele T-46 (FY+) but this was not observed with the P. vivax infection. P. vivax was ruled out in all FY- individuals.

INTRODUCCIÓN: La condición homocigótica negativa del grupo sanguíneo Duffy ((Fy-/Fy-) confiere resistencia natural a Plasmodium vivax. En este sentido, los estudios realizados en Colombia son escasos. OBJETIVO: describir la relación entre los genotipos Duffy en tres comunidades étnicas de La Italia (Chocó), y la malaria. MÉTODOS: estudio descriptivo, transversal con individuos sintomáticos o asintomáticos de malaria. Tamaño muestral por etnia: afrocolombiana 73; amerindia 74, mestiza 171. La infección plasmodial se estudió por gota gruesa y el estado del gen Duffy por PCR y RFLP con el fin de identificar los cambios T-46C y A131G que originan los genotipos T/T, T/C , C/C y G/G, G/A, A/A. RESULTADOS: se encontró infección plasmodial en 17% con 62% por P. falciparum y 27% por P. vivax. Se halló relación entre genotipos Duffy y etnia (p= 0.003). Los individuos con diplotipos C/C,A/A se infectaron exclusivamente con P. falciparum, mientras que otros diplotipos por las dos especies. En amerindios y mestizos la frecuencia del alelo T-46 fue 0.90-1.00, en afrocolombianos fue 0.50, al igual que el alelo C, con ausencia de heterocigotos. En el locus 131 la máxima frecuencia del alelo G fue 0.30 en amerindios y la máxima del alelo A fue 0.69 en afrocolombianos. CONCLUSIONES: En las poblaciones amerindia y mestiza estudiadas predomina el alelo T-46 (FY+), pero no predomina en ellas la infección por P. vivax. Ningún individuo FY- tuvo infección por P. vivax.

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Malaria is an acute infectious disease caused by the protozoa of the genus Plasmodium. The antigens of the Duffy Blood Group System, in addition to incompatibilities in transfusions and hemolytic disease of the newborn, are of great interest in medicine due to their association with the invasion of red blood cells by the parasite Plasmodium vivax. For invasions to occur an interaction between the parasites and antigens of the Duffy Blood Group System is necessary. In Caucasians six antigens are produced by the Duffy locus (Fya, Fyb, F3, F4, F5 and F6). It has been observed that Fy(a-b-) individuals are resistant to Plasmodium knowlesi and P. vivax infection, because the invasion requires at least one of these antigens. The P. vivax Duffy Binding Protein (PvDBP) is functionally important in the invasion process of these parasites in Duffy / DARC positive humans. The proteins or fractions may be considered, therefore, an important and potential inoculum to be used in immunization against malaria.

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Malaria is an acute infectious disease caused by the protozoa of the genus Plasmodium. The antigens of the Duffy Blood Group System, in addition to incompatibilities in transfusions and hemolytic disease of the newborn, are of great interest in medicine due to their association with the invasion of red blood cells by the parasite Plasmodium vivax. For invasions to occur an interaction between the parasites and antigens of the Duffy Blood Group System is necessary. In Caucasians six antigens are produced by the Duffy locus (Fya, Fyb, F3, F4, F5 and F6). It has been observed that Fy(a-b-) individuals are resistant to Plasmodium knowlesi and P. vivax infection, because the invasion requires at least one of these antigens. The P. vivax Duffy Binding Protein (PvDBP) is functionally important in the invasion process of these parasites in Duffy / DARC positive humans. The proteins or fractions may be considered, therefore, an important and potential inoculum to be used in immunization against malaria.

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Duffy gene (FY) codifies the transmembrane glycoprotein Duffy (gp-Fy) of 35 to 43 kDa which is moderately immunogenic. This glycoprotein is polymorphic, and constitutes the antigens of the Duffy histo-blood system which were designated receptors for chemokines and denominated DARC (Duffy antigen/receptor for chemokine). This receptor has an important role in the regulation of chemokine levels in the circulation, as it binds and adsorbs them on the surface of red cells as a reservoir. It plays a "sink" role, which can contribute to homeostasis by removing inflammatory chemokines from circulation as well as maintaining them in plasmatic levels. Chronic Chagas' cardiopathy (CCC) is the most frequent form of the disease. It is an inflammatory disease, in which infiltrated inflammatory cells play an important role in the development and progress of the infection. High chemokine levels in the plasma have been associated with the disease severity in patients with heart failure. In this context, the profile of DARC expression could play an important function as a receptor for chemokines in Chagas' disease, in patients with CCC, as it can modulate damage from this inflammatory disease.(AU)

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Duffy gene (FY) codifies the transmembrane glycoprotein Duffy (gp-Fy) of 35 to 43 kDa which is moderately immunogenic. This glycoprotein is polymorphic, and constitutes the antigens of the Duffy histo-blood system which were designated receptors for chemokines and denominated DARC (Duffy antigen/receptor for chemokine). This receptor has an important role in the regulation of chemokine levels in the circulation, as it binds and adsorbs them on the surface of red cells as a reservoir. It plays a "sink" role, which can contribute to homeostasis by removing inflammatory chemokines from circulation as well as maintaining them in plasmatic levels. Chronic Chagas' cardiopathy (CCC) is the most frequent form of the disease. It is an inflammatory disease, in which infiltrated inflammatory cells play an important role in the development and progress of the infection. High chemokine levels in the plasma have been associated with the disease severity in patients with heart failure. In this context, the profile of DARC expression could play an important function as a receptor for chemokines in Chagas' disease, in patients with CCC, as it can modulate damage from this inflammatory disease.

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Duffy blood group genotype was studied in 95 unrelated subjects from four African-Brazilian communities of the Amazon region: Trombetas, Pitimandeua, Curiaú, and Mazagão Velho. Genotyping was performed using an allele-specific primer polymerase chain reaction technique for determining the three major alleles at FY blood group, and as expected, FY*O allele was the most common one, with frequencies ranging from 56.4% in Mazagão Velho to 72.2% in Pitimandeua, whereas the FY*O/FY*O genotype was found with frequencies between 32.3% in Mazagão Velho and 58.8% in Curiaú. Genotype and allele distributions in the four Amazonian communities are consistent with a predominantly African origin with some degree of local differentiation and admixture with people of Caucasian ancestry and/or Amerindians. These results reveal that the impact of the FY*O/FY*O genotype on the transmission and endemicity of the vivax malaria deserves to be investigated in full detail in an attempt to identify the contribution of host biological factors and explain the non-homogeneous prevalence of malaria in the region expressed by its different levels of exposure

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Ala100Thr has been suggested to be a Caucasian genetic marker on the FY*B allele. As the Brazilian population has arisen from miscegenation among Portuguese, Africans, and Indians, this mutation could possibly be found in Euro- and Afro-Brazilians, or in Brazilian Indians. Fifty-three related individuals and a random sample of 100 subjects from the Brazilian population were investigated using the polymerase chain reaction and four restriction fragment length polymorphisms. Confirming the working hypothesis, among the related individuals three Afro-Brazilians (two of them a mother and daughter) and a woman of Amerindian descent had the Ala100Thr mutation on the FY*B allele. Five non-related Euro-Brazilians also carried the mutation. All nine individuals presented the Fy(a-b+) phenotype. We conclude that the Ala100Thr mutation can occur in populations other than Caucasians and that this mutation does not affect Duffy expression on red blood cells. Gene frequencies for this allele in the non-related individuals were in agreement with those of other populations. The Duffy frequencies of two Amerindian tribes were also investigated.

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