RESUMO
Identification of biomarkers associated with severity in sickle cell anemia is desirable. Circulating serum microRNAs (miRNA) are targets studied as diagnostic or prognostic markers, but few studies have been conducted in sickle cell anemia. The purpose of this study is to identify specific signatures of miRNAs in plasma samples from sickle cell anemia patients according to severity indexes. Screening of the miRNAs expression was performed in 8 patients, classified by tricuspid regurgitation velocity (TRV) measure: 4 with TRV ≥ 2.5 m/s and 4 with TRV < 2.5 m/s. The samples were analyzed by real-time PCR using Megaplex RT Human Pool A and Pool B comprising 667 distinct miRNAs. Seventeen miRNAs were differentially expressed between the two groups (p < 0.05). Five differentially expressed miRNAs (miR15b, miR502, miR510, miR544, miR629) were selected for validation in a cohort of 52 patient samples, 26 with TRV ≥ 2.5 m/s. Another two severity scores were also used: organ injury score (OIS) and Bayesian score (BS). Univariate binary logistic regressions were performed to analyze the data. Five out of 17 differentially expressed miRNAs were selected for validation in 52 patient samples: miR15b, miR502, miR510, miR544, and miR629. Two miRNAs (miR510 and miR629) were significantly decreased in cases of greater severity. Whereas miR510 expression discriminated the patients according to TRV and OIS, miR629 expression did it according to BS. This is the first study investigating plasma miRNAs as possible biomarkers for SCA severity. Our data suggest that low levels of miR510 and miR629 expression are associated with greater SCA disease severity. Further studies are still necessary to elucidate mechanism of these miRNAs and their related proteins.
Assuntos
Anemia Falciforme/genética , MicroRNAs/genética , Transcriptoma , Adolescente , Adulto , Idoso , Anemia Falciforme/sangue , Anemia Falciforme/diagnóstico , Teorema de Bayes , Feminino , Humanos , Masculino , MicroRNAs/sangue , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Índice de Gravidade de Doença , Adulto JovemRESUMO
Erythrocytes from sickle cell anaemia (SCA) patients continuously produce larger amounts of pro-oxidants than normal cells. Oxidative stress seems to primarily affect the membrane and results in haemolysis. The use of antioxidants in vitro reduces the generation of pro-oxidants. To evaluate the impact of vitamins C (VitC) and E (VitE) supplementation in SCA patients, patients over 18 years were randomly assigned to receive VitC 1400 mg + VitE 800 mg per day or placebo orally for 180 d. Eighty-three patients were enrolled (44 vitamins, 39 placebo), median age 27 (18-68) years, 64% female. There were no significant differences between the two groups regarding clinical complications or baseline laboratorial tests. Sixty percent of the patients were VitC deficient, 70% were VitE deficient. Supplementation significantly increased serum VitC and E. However, no significant changes in haemoglobin levels were observed, and, unexpectedly, there was a significant increase in haemolytic markers with vitamin supplementation. In conclusion, VitC + VitE supplementation did not improve anaemia and, surprisingly, increased markers of haemolysis in patients with SCA and S-ß(0) -thalassaemia. The exact mechanisms to explain this findings and their clinical significance remain to be determined.
Assuntos
Anemia Falciforme/sangue , Antioxidantes/efeitos adversos , Ácido Ascórbico/efeitos adversos , Suplementos Nutricionais/efeitos adversos , Hemólise/efeitos dos fármacos , Vitamina E/efeitos adversos , Adolescente , Adulto , Idoso , Anemia Falciforme/tratamento farmacológico , Antioxidantes/administração & dosagem , Antioxidantes/uso terapêutico , Ácido Ascórbico/administração & dosagem , Ácido Ascórbico/uso terapêutico , Biomarcadores , Método Duplo-Cego , Uso de Medicamentos/estatística & dados numéricos , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Inflamação/sangue , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Qualidade de Vida , Espécies Reativas de Oxigênio , Traço Falciforme/sangue , Traço Falciforme/tratamento farmacológico , Traço Falciforme/genética , Talassemia/sangue , Talassemia/tratamento farmacológico , Talassemia/genética , Vitamina E/administração & dosagem , Vitamina E/uso terapêutico , Adulto JovemAssuntos
Anemia Falciforme/sangue , Anemia Falciforme/patologia , Hemólise , L-Lactato Desidrogenase/sangue , Adulto , Anemia Falciforme/tratamento farmacológico , Anemia Falciforme/enzimologia , Antidrepanocíticos/uso terapêutico , Biomarcadores/sangue , Pré-Escolar , Feminino , Hemólise/efeitos dos fármacos , Humanos , Hidroxiureia/uso terapêutico , Isoenzimas/sangue , Masculino , Adulto JovemAssuntos
Anemia Falciforme/genética , Anemia Falciforme/imunologia , Sistema do Grupo Sanguíneo Duffy/genética , Receptores de Superfície Celular/genética , Adulto , Anemia Falciforme/sangue , Brasil , Sistema do Grupo Sanguíneo Duffy/sangue , Feminino , Hemólise , Humanos , Masculino , Mutação , Fenótipo , Receptores de Superfície Celular/sangueRESUMO
BACKGROUND: Haptoglobin genotypes, and interleukin-6 and -8 participate in the pathophysiology of sickle cell anemia. The expression of cytokines is regulated by genetic mechanisms however the effect of haptoglobin polymorphisms on these cytokines is not fully understood. This study aimed to compare the frequency of haptoglobin genotypes and the interleukin-6 and -8 concentrations in sickle cell anemia patients and controls to investigate the association between haptoglobin genotypes and cytokine levels. METHODS: Sixty sickle cell anemia patients and 74 healthy individuals were analyzed. Haptoglobin genotypes were determined by multiplex polymerase chain reaction, and the interleukin-6 and -8 levels by enzyme linked immunosorbent assay. The association between haptoglobin genotypes and cytokines was investigated by statistical tests. RESULTS: Hp2-1 was the most common genotype in both the cases and controls while Hp1-1 was less frequent among sickle cell anemia patients. Interleukin-6 and -8 levels were higher in patients than controls (p-value <0.0001). There was no significant difference in interleukin-6 and -8 concentrations between the genotypes (p-value >0.05). A similar trend was observed among the controls. CONCLUSION: Although, levels of interleukin-6 and -8 were higher in the sickle cell anemia patients, they appeared not to be related to the haptoglobin genotypes. Further investigations are necessary to identify factors responsible for increased secretion of the interleukin-6 and -8 pro-inflammatory cytokines in patients with sickle cell anemia.
RESUMO
BACKGROUND: Haptoglobin genotypes, and interleukin-6 and -8 participate in the pathophysiology of sickle cell anemia. The expression of cytokines is regulated by genetic mechanisms however the effect of haptoglobin polymorphisms on these cytokines is not fully understood. This study aimed to compare the frequency of haptoglobin genotypes and the interleukin-6 and -8 concentrations in sickle cell anemia patients and controls to investigate the association between haptoglobin genotypes and cytokine levels.METHODS: Sixty sickle cell anemia patients and 74 healthy individuals were analyzed. Haptoglobin genotypes were determined by multiplex polymerase chain reaction, and the interleukin-6 and -8 levels by enzyme linked immunosorbent assay. The association between haptoglobin genotypes and cytokines was investigated by statistical tests.RESULTS:Hp2-1 was the most common genotype in both the cases and controls while Hp1-1 was less frequent among sickle cell anemia patients. Interleukin-6 and -8 levels were higher in patients than controls (p-value <0.0001). There was no significant difference in interleukin-6 and -8 concentrations between the genotypes (p-value >0.05). A similar trend was observed among the controls.CONCLUSION: Although, levels of interleukin-6 and -8 were higher in the sickle cell anemia patients, they appeared not to be related to the haptoglobin genotypes. Further investigations are necessary to identify factors responsible for increased secretion of the interleukin-6 and -8 pro-inflammatory cytokines in patients with sickle cell anemia.