Perfil leucocitário em portadores de hemoglobina S e de mutações no Gene HFE (H63D, C282Y e S65C)
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Data
2022-01-25
Autores
Ribeiro, Thaís Fernandes
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Editor
Universidade Estadual Paulista (Unesp)
Resumo
Doença falciforme (DF) designa o conjunto de distúrbios hereditários que advém de
mutações nos precursores eritróides com prevalência de hemoglobina S, caracterizada por
mutação no gene beta globina. A hemoglobina S em homozigose (Hb SS) denomina a anemia
falciforme (AF) e tem como consequência clínica anemia hemolítica crônica e sintomas
variáveis. Para o tratamento é utilizado a hidroxiuréia (HU), única medicação com impacto na
melhora da qualidade de vida dos pacientes. Devido à importância dos processos inflamatórios
e dos fenômenos vaso-oclusivos, busca-se relacionar a doença falciforme com a
hemocromatose hereditária a fim de identificar pacientes com maior risco de desenvolver
quadros graves, pelo perfil de leucócitos (NLR). Tendo em vista que a hemocromatose
hereditária está intimamente relacionada com os processos de homeostase do ferro celular e que
pacientes com polimorfismos no gene HFE (C282Y, H63D e S65C) podem desenvolver uma
série de doenças inflamatórias e neuronais, justifica-se a avaliação leucocitária em pessoas com
anemia falciforme. Para tanto, foi necessário estabelecer a relação do genótipo de doença
falciforme com o genótipo das mutações no gene HFE por meio de análise molecular indicando
a possível gravidade clínica, mediante calculadora de gravidade da DF, e definir a expressão
fenotípica da AF em pacientes em uso e sem uso de HU e a concentração de ferritina com o
índice leucocitário. O estudo envolveu 516 pacientes, com idades entre 6 e 65 anos,
provenientes do estado do Rio de Janeiro. Os resultados mostraram que para a anemia
falciforme, nenhuma associação foi encontrada entre a heterozigose e homozigose para os
polimorfismos do gene HFE e a análise de frequência exibiu o equilíbrio entre os alelos. Com
relação à gravidade da doença, a mutação H63D apresentou diferença significativa e as
mutações C282Y e S65C não; A baixa frequência em populações miscigenadas pode explicar o
resultado. O gênero apresentou relação com o número de neutrófilos e linfócitos em uso ou não
de HU. A associação do NLR com a ferritina demonstrou diferenças, indicando que casos
graves de AF podem agravar a absorção de ferro. Já as variáveis gênero, presença ou ausência
da mutação H63D, o uso ou não de hidroxiuréia e a gravidade da doença, não demonstraram diferenças. No entanto, as mutações no gene HFE podem influenciar no processo inflamatório
da doença e o tratamento com HU diminui o NLR e contribui para uma diminuição do risco de
morte, visto que o aumento do número de neutrófilos pode promover crises vaso-oclusivas. Este
estudo enfatiza a importância do desenvolvimento de mais estudos sobre o efeito da HH na AF
e sua relação com o NLR. Traçar o perfil dos portadores que estão predispostos a desenvolverem quadros clínicos mais graves permite aos profissionais da saúde traçar estratégias para um suporte mais eficaz.
Sickle cell disease (SCD) designates the set of hereditary disorders that result from mutations in erythroid precursors with prevalence of hemoglobin S, characterized by a mutation in the beta globin gene. Hemoglobin S in homozygosis (Hb SS) is called sickle cell anemia (SCA) and its clinical consequence of chronic hemolytic anemia and variable symptoms. For the treatment, hydroxyurea (HU) is used, the Only medication with impact on improving the quality of life of patients. Due to the importance of inflammatory processes and vaso-occlusive phenomena, an attempt is made to relate sickle cell disease with hereditary hemochromatosis in order to identify patients at higher risk of developing severe conditions, based on the leukocyte profile (NLR). Considering that hereditary hemochromatosis is closely related to cellular iron homeostasis processes and that patients with polymorphisms in the HFE gene (C282Y, H63D and S65C) can develop a series of inflammatory and neuronal diseases, leukocyte evaluation in people with sickle cell anemia is justified. Therefore, it was necessary to establish the relationship between the sickle cell disease genotype with the genotype of mutations in the HFE gene through molecular analysis indicating the possible clinical severity, using a SCD severity calculator, and to define the phenotypic expression of SCA in patients using and not using HU and the ferritin concentration with the leukocyte index. The study involved 516 patients, aged between 6 and 65 years, from the state of Rio de Janeiro. The results showed that for sickle cell anemia, no association was found between heterozygosity and homozygosity for the HFE gene polymorphisms and frequency analysis showed the balance between the alleles. Regarding disease severity, the H63D mutation showed a significant difference and the C282Y and S65C mutations did not; The low frequency in mixed populations may explain the result. Gender was related to the number of neutrophils and lymphocytes using or not HU. The association of the NLR with ferritin showed diferences, indicating that severe cases of SCA can worsen iron absorption. While the variables gender, presence or absence of the H63D mutation, the use or not of hydroxyurea and severity of the disease did not show differences. However, mutations in the HFE gene can influence the inflammatory process of the disease and treatment with HU decreases the NLR and contributes to a decrease in the risk of death, since the increase in the number of neutrophils can promote vaso-occlusive crises. This study emphasizes the importance of developing more studies on the effect of HH on SCA and its relationship with the NLR. Tracing the profile of patients who are predisposed to developing more severe clinical conditions allows health professionals to devise strategies for more effective support.
Sickle cell disease (SCD) designates the set of hereditary disorders that result from mutations in erythroid precursors with prevalence of hemoglobin S, characterized by a mutation in the beta globin gene. Hemoglobin S in homozygosis (Hb SS) is called sickle cell anemia (SCA) and its clinical consequence of chronic hemolytic anemia and variable symptoms. For the treatment, hydroxyurea (HU) is used, the Only medication with impact on improving the quality of life of patients. Due to the importance of inflammatory processes and vaso-occlusive phenomena, an attempt is made to relate sickle cell disease with hereditary hemochromatosis in order to identify patients at higher risk of developing severe conditions, based on the leukocyte profile (NLR). Considering that hereditary hemochromatosis is closely related to cellular iron homeostasis processes and that patients with polymorphisms in the HFE gene (C282Y, H63D and S65C) can develop a series of inflammatory and neuronal diseases, leukocyte evaluation in people with sickle cell anemia is justified. Therefore, it was necessary to establish the relationship between the sickle cell disease genotype with the genotype of mutations in the HFE gene through molecular analysis indicating the possible clinical severity, using a SCD severity calculator, and to define the phenotypic expression of SCA in patients using and not using HU and the ferritin concentration with the leukocyte index. The study involved 516 patients, aged between 6 and 65 years, from the state of Rio de Janeiro. The results showed that for sickle cell anemia, no association was found between heterozygosity and homozygosity for the HFE gene polymorphisms and frequency analysis showed the balance between the alleles. Regarding disease severity, the H63D mutation showed a significant difference and the C282Y and S65C mutations did not; The low frequency in mixed populations may explain the result. Gender was related to the number of neutrophils and lymphocytes using or not HU. The association of the NLR with ferritin showed diferences, indicating that severe cases of SCA can worsen iron absorption. While the variables gender, presence or absence of the H63D mutation, the use or not of hydroxyurea and severity of the disease did not show differences. However, mutations in the HFE gene can influence the inflammatory process of the disease and treatment with HU decreases the NLR and contributes to a decrease in the risk of death, since the increase in the number of neutrophils can promote vaso-occlusive crises. This study emphasizes the importance of developing more studies on the effect of HH on SCA and its relationship with the NLR. Tracing the profile of patients who are predisposed to developing more severe clinical conditions allows health professionals to devise strategies for more effective support.
Descrição
Palavras-chave
Sickle cell disease, Hereditary hemochromatosis, Sickle cell anemia, Leukocyte profile, Doença falciforme, Hemocromatose hereditária, Anemia falciforme, Perfil de leucócitos