Interaction between smoking and HLA-DRB1*04 gene is associated with a high cardiovascular risk in Brazilian Amazon patients with rheumatoid arthritis

Background: Rheumatoid Arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the joints that affects approximately 1% of the population worldwide. The HLA-DRB1 gene locus plays a major role in genetic susceptibility to RA, a condition that has been associated with a high cardiovascular morbidity and mortality in many studies. Methodology/Principal Findings: The aim of this work was to investigate which types of HLA class II genes are associated with RA in patients from the Brazilian Amazon and their influence on high cardiovascular risk status in this population. For this purpose, a case-control study was carried out with a total of 350 non-Indian individuals made up of a cohort of 132 consecutive RA sufferers and 218 healthy controls. A χ2 test showed that HLADRB1*04 (p<0.0016; OR = 1.89; 95% CI = 1.29-2.79) and HLADRB1*10 (p = 0.0377; OR = 3.81; 95% CI = 1.16-12.50) are the major HLA genes associated with susceptibility to RA. A logistic regression model also showed that the interaction between HLADRB1*04 (p = 0.027; OR = 6.02; 95% CI = 1.21-29.7), age (p = 0.0001; OR = 1.26; 95% CI = 1.13-1.39) and smoking (p = 0.0001; OR = 23.6; 95% CI = 4.25-32.1) is associated with a probability of a high cardiovascular risk status at an early age. Conclusions/Significance: The results of this study show for the first time that HLA class II type is associated with RA in Brazilian Amazon populations and that a specific interaction between the HLA-DRB1*04 gene and smoking is associated with a high cardiovascular risk status, as initially reported in the European population. This study therefore contributes to an understanding of gene-environment interactions in RA patients. © 2012 Boechat et al

IMUNOTERAPIAS NO TRATAMENTO DA COVID-19

A COVID-19 é uma doença causada pelo novo coronavírus e se tornou-se ameaça mundial pouco tempo após seu surgimento na cidade chinesa de Wuhan. Desde Dezembro de 2019, diversas pesquisas estão sendo realizadas com o propósito de conter a disseminação do vírus e de se obter medidas de tratamento úteis no combate à pandemia. Com isso, o presente estudo volta-se para a análise das novas metodologias de caráter terapêutico que estão sendo desenvolvidas mundialmente para o tratamento e prevenção da COVID-19. A presente revisão bibliográfica foi realizada com os dados obtidos nas seguintes bases: SciELO, Medline, Scopus,  Up-to-Date, dentre outros recursos atuais e relevantes para a temática, que foram publicados no primeiro trimestre do ano de 2020. Com esta abordagem foram identificadas diversas abordagens de tratamento ainda em desenvolvimento, com diferentes modelos, bem como mecanismo de ação de novas medidas terapêuticas e de imunização, sobretudo, as que utilizam soro, imunoglobulinas, anticorpos monoclonais, plasma de pacientes convalescentes e vacinas. O sistema de saúde mundial urge pela criação de uma vacina capaz de estabelecer a memória imunológica na população. Novos estudos mostram-se promissores em relação a essa criação, todavia, as medidas profiláticas permanecem como prioridade máxima e indispensáveis.&nbsp

Interaction between Smoking and HLA-DRB1*04 Gene Is Associated with a High Cardiovascular Risk in Brazilian Amazon Patients with Rheumatoid Arthritis

BACKGROUND: Rheumatoid Arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the joints that affects approximately 1% of the population worldwide. The HLA-DRB1 gene locus plays a major role in genetic susceptibility to RA, a condition that has been associated with a high cardiovascular morbidity and mortality in many studies. METHODOLOGY/PRINCIPAL FINDINGS: The aim of this work was to investigate which types of HLA class II genes are associated with RA in patients from the Brazilian Amazon and their influence on high cardiovascular risk status in this population. For this purpose, a case-control study was carried out with a total of 350 non-Indian individuals made up of a cohort of 132 consecutive RA sufferers and 218 healthy controls. A χ(2) test showed that HLADRB1*04 (p<0.0016; OR = 1.89; 95% CI = 1.29–2.79) and HLADRB1*10 (p = 0.0377; OR = 3.81; 95% CI = 1.16–12.50) are the major HLA genes associated with susceptibility to RA. A logistic regression model also showed that the interaction between HLADRB1*04 (p = 0.027; OR = 6.02; 95% CI = 1.21–29.7), age (p = 0.0001; OR = 1.26; 95% CI = 1.13–1.39) and smoking (p = 0.0001; OR = 23.6; 95% CI = 4.25–32.1) is associated with a probability of a high cardiovascular risk status at an early age. CONCLUSIONS/SIGNIFICANCE: The results of this study show for the first time that HLA class II type is associated with RA in Brazilian Amazon populations and that a specific interaction between the HLA-DRB1*04 gene and smoking is associated with a high cardiovascular risk status, as initially reported in the European population. This study therefore contributes to an understanding of gene-environment interactions in RA patients

ROC curve for the general genetic model for RA susceptibility (AUC 0.70).

<p>ROC curve for the general genetic model for RA susceptibility (AUC 0.70).</p

Analysis of ClassII HLA and its association with rheumatoid arthritis^*.

*<p>χ²test, significance level <i>p</i><0.05.</p

ROC curves comparing the accuracy of the two regression models.

<p>Smoking status is included in the second model.</p