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HLA-DRB1*1501 : an association with multiple sclerosis
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Background: Foi demonstrado que a prevalência da esclerose múltipla (EM) está associada ao haplótipo DRB1*1501 do complexo principal de histocompatibilidade classe II. Adicionalmente, o perfil do micobioma dos doentes com EM revelou ser diferente do micobioma das pessoas sem a doença.
Objetivo: Avaliar se o polimorfismo de um único nucleótido (SNP) HLA-DRB1*1501 está associado ao aparecimento de EM, numa coorte específica de Controlos Saudáveis (CS) e de doentes com EM. Para além disso, se existem diferenças no perfil do micobioma entre os doentes com EM que apresentam o SNP HLA-DRB1*1501 em comparação com os que não apresentam.
Métodos: Os doentes com EM (n=185) e os controlos saudáveis (HC) (n=279) foram genotipados para o HLA-DRB1*1501 sendo que para as análises de potenciais diferenças associadas ao sexo foram considerados 182 doentes com EM e 248 HC. Os resultados da genotipagem foram combinados com as análises do ADN do micobioma, obtidas por uma plataforma bioinformática que utiliza uma análise ITS. Foram igualmente avaliadas as concentrações séricas de calprotectina e quitotriosidase com recurso a Enzyme-linked immunosorbent assays (ELISAs).
Resultados: Os dados confirmam uma maior possibilidade de desenvolver EM pela presença do SNP HLA-DRB1*1501 (OR=1,718) e esta possibilidade é maior no sexo feminino do que no masculino (OR=1,842). Além disso, foi demonstrada uma diferença considerável no perfil do micobioma entre os doentes com EM com o SNP versus aqueles sem o SNP HLA-DRB1*1501. Relativamente ao micobioma a classe Saccharomycetes apresentou uma percentagem mais elevada em indivíduos com o SNP, enquanto os géneros Candida e Aspergillus parecem desempenhar um papel no desenvolvimento da EM em doentes com o SNP. Não foram observadas diferenças significativas entre a presença e a ausência do SNP relativamente à diversidade ou riqueza de fungos, ao rácio Basidiomycota/Ascomycota ou às concentrações de calprotectina e quitotriosidase.
Conclusões: Os indivíduos com o SNP HLA-DRB1*1501 têm maior possibilidade de desenvolver EM, de modo mais marcante para as mulheres. O perfil do micobioma entre os doentes com EM com o SNP e sem o SNP HLA-DRB1*1501 é diferente.
Background: The prevalence of multiple sclerosis (MS) has been shown to be associated with the major histocompatibility complex class II DRB1*1501 haplotype. Additionally, the mycobiome profile of MS patients has proven to be different from the mycobiome of people without the disease. Objective: To assess whether the single nucleotide polymorphism (SNP) HLA-DRB1*1501 is associated with the emergence of MS, in a specific cohort of Healthy Controls (HC) and MS patients. Furthermore, if there are differences in the mycobiome profile between MS patients that present the SNP HLA-DRB1*1501 in comparison with the ones that does not. Methods: MS patients (n=185) and healthy controls (HC) (n=279) were genotyped for HLA-DRB1*1501, and from those 182 patients with MS and 248 HC were considered to assess potential sex-associated differences. The genotyping results were combined with the analyses of mycobiome DNA, obtained by a bioinformatic platform using an ITS analysis. The concentrations of calprotectin and chitotriosidase were evaluated in the serum by using Enzyme-linked immunosorbent assays (ELISAs). Results: The data confirms a higher possibility of developing MS by the presence of the SNP HLA-DRB1*1501 (OR=1,718) being this possibility higher in females than in males (OR=1,842). Also, a considerable difference in mycobiome profile between MS patients with the SNP and without the SNP HLA-DRB1*1501 has been demonstrated. Saccharomycetes class showed a higher percentage in individuals with the SNP, while Candida and Aspergillus genera may play a role in the development of MS in MS patients with the SNP. No significant differences were observed between the presence or absence of the SNP concerning the diversity or richness of fungi, the ratio Basidiomycota/Ascomycota, and the concentrations of calprotectin and chitotriosidase. Conclusions: Individuals with the SNP HLA-DRB1*1501 have a higher possibility of developing MS, with a higher magnitude in females. The mycobiome profile between MS patients with the SNP and without the SNP HLA-DRB1*1501 is different.
Background: The prevalence of multiple sclerosis (MS) has been shown to be associated with the major histocompatibility complex class II DRB1*1501 haplotype. Additionally, the mycobiome profile of MS patients has proven to be different from the mycobiome of people without the disease. Objective: To assess whether the single nucleotide polymorphism (SNP) HLA-DRB1*1501 is associated with the emergence of MS, in a specific cohort of Healthy Controls (HC) and MS patients. Furthermore, if there are differences in the mycobiome profile between MS patients that present the SNP HLA-DRB1*1501 in comparison with the ones that does not. Methods: MS patients (n=185) and healthy controls (HC) (n=279) were genotyped for HLA-DRB1*1501, and from those 182 patients with MS and 248 HC were considered to assess potential sex-associated differences. The genotyping results were combined with the analyses of mycobiome DNA, obtained by a bioinformatic platform using an ITS analysis. The concentrations of calprotectin and chitotriosidase were evaluated in the serum by using Enzyme-linked immunosorbent assays (ELISAs). Results: The data confirms a higher possibility of developing MS by the presence of the SNP HLA-DRB1*1501 (OR=1,718) being this possibility higher in females than in males (OR=1,842). Also, a considerable difference in mycobiome profile between MS patients with the SNP and without the SNP HLA-DRB1*1501 has been demonstrated. Saccharomycetes class showed a higher percentage in individuals with the SNP, while Candida and Aspergillus genera may play a role in the development of MS in MS patients with the SNP. No significant differences were observed between the presence or absence of the SNP concerning the diversity or richness of fungi, the ratio Basidiomycota/Ascomycota, and the concentrations of calprotectin and chitotriosidase. Conclusions: Individuals with the SNP HLA-DRB1*1501 have a higher possibility of developing MS, with a higher magnitude in females. The mycobiome profile between MS patients with the SNP and without the SNP HLA-DRB1*1501 is different.
Descrição
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, 2023, Universidade de Lisboa, Faculdade de Farmácia.
Palavras-chave
Multiple sclerosis Gene Single nucleotide polymorphism HLADRB1*1501 Mycobiome Mestrado Integrado - 2023