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ABSTRACT Introduction Blood donor screening is an important stage of quality control in blood banks. Turbidity caused by increased levels of triglycerides is detected by visual inspection, but there is no consensus on its threshold at which plasma should be considered inappropriate for donation. Objective Compare triglycerides dosage and visual turbidity in decision making for the disposal of plasma. Material and methods Plasma bags (n=205) were classified by visual inspection as clear, moderately turbid or turbid and triglyceride concentration were determined in serum and plasma with enzimatic-colorimetric methodology by automation. Results Our results show a positive correlation between serum and plasma triglycerides levels (r=0,94) but we observed a higher concentration in serum when compared to plasma samples (p<0,03). Most of the plasma were classified as moderately turbid or turbid (75%). Visual inspection and triglycerides levels were moderately correlated in serum (rb=0,57) and plasma (rb=0,52). However, moderately turbid samples showed discordance between serum or plasma triglyceride levels and the visual inspection. Discussion Our findings corroborate with the literature data, supporting the subjectivity of the visual inspection. We recommend further studies to determine which triglyceride threshold should be used for the disposal of plasma bags combined with automated methods to enhance visual classification accuracy. Conclusion Quality improvement actions are critical for standardization of the screening in order to avoid unnecessary disposal of the plasma bags.
RESUMO Introdução A triagem das bolsas de plasma é uma etapa importante do controle de qualidade nos hemocentros. A turbidez causada pelo aumento de triglicerídeos é detectada por inspeção visual, mas não há consenso acerca do limite no qual o plasma deve ser considerado inadequado para doação. Objetivo Comparar a dosagem de triglicerídeos e a turbidez visual na tomada de decisão para o descarte do plasma. Material e métodos As bolsas de plasma (n=205) foram classificadas pela inspeção visual como límpidas, moderadamente turvas ou turvas e as concentrações de triglicerídeos foram determinadas no soro e plasma com metodologia enzimática-colorimétrica por automação. Resultados Nossos resultados mostraram uma correlação positiva entre soro e plasma (r=0,94) mas observamos que a concentração de triglicerídeos foi mais alta no soro do que no plasma (p<0,03). A maioria das bolsas foi classificada como moderadamente turva ou turva (75%). A inspeção visual e a concentração de triglicerídeos apresentaram uma correlação moderada para o soro (rb=0,57) e plasma (rb=0,52). Entretanto, no grupo moderadamente turvo, houve uma divergência significativa entre as concentrações de triglicerídeos no soro/plasma e a inspeção visual. Discussão Nossos achados corroboram com a literatura, reforçando a subjetividade da inspeção visual. Nós recomendamos a realização de estudos futuros para determinar o limite dos níveis de triglicerídeos para o descarte de plasma em conjunto com a combinação de métodos automatizados para aumentar a acurácia da classificação visual. Conclusão As ações voltadas para a melhoria da qualidade são críticas para a padronização da triagem e evitar o descarte desnecessário de plasma.
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Several genome-wide association studies (GWAS) have been carried out with late-onset Alzheimer's disease (LOAD), mainly in European and Asian populations. Different polymorphisms were associated, but several of them without a functional explanation. GWAS are fundamental for identifying loci associated with diseases, although they often do not point to causal polymorphisms. In this sense, functional investigations are a fundamental tool for discovering causality, although the failure of this validation does not necessarily indicate a non-causality. Furthermore, the allele frequency of associated genetic variants may vary widely between populations, requiring replication of these associations in other ethnicities. In this sense, our study sought to replicate in 150 AD patients and 114 elderly controls from the South Brazilian population 18 single-nucleotide polymorphisms (SNPs) associated with AD in European GWAS, with further functional investigation using bioinformatic tools for the associated SNPs. Of the 18 SNPs investigated, only four were associated in our population: rs769449 (APOE), rs10838725 (CELF1), rs6733839, and rs744373 (BIN1-CYP27C1). We identified 54 variants in linkage disequilibrium (LD) with the associated SNPs, most of which act as expression or splicing quantitative trait loci (eQTLs/sQTLs) in genes previously associated with AD or with a possible functional role in the disease, such as CELF1, MADD, MYBPC3, NR1H3, NUP160, SPI1, and TOMM40. Interestingly, eight of these variants are located within long non-coding RNA (lncRNA) genes that have not been previously investigated regarding AD. Some of these polymorphisms can result in changes in these lncRNAs' secondary structures, leading to either loss or gain of microRNA (miRNA)-binding sites, deregulating downstream pathways. Our pioneering work not only replicated LOAD association with polymorphisms not yet associated in the Brazilian population but also identified six possible lncRNAs that may interfere in LOAD development. The results lead us to emphasize the importance of functional exploration of associations found in large-scale association studies in different populations to base personalized and inclusive medicine in the future.
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BACKGROUND: Mannan-binding lectin (MBL) - associated serine protease 2 (MASP-2) co-activates the lectin pathway of complement in response to several viral infections. The quality of this response partly depends on MASP2 gene polymorphisms, which modulate MASP-2 function and serum levels. In this study we investigated a possible role of MASP2 polymorphisms, MASP-2 serum levels and MBL-mediated complement activation in the susceptibility to HIV/AIDS and HBV/HCV coinfection. METHODS: A total of 178 HIV patients, 89 (50%) coinfected with HBV/HCV, 51.7% female, average age 40 (12-73) years, and 385 controls were evaluated. MASP-2 levels and MBL-driven complement activation were evaluated by enzyme-linked immunosorbent assay and 11 MASP2 polymorphisms from the promoter to the last exon were haplotyped using multiplex sequence-specific PCR. RESULTS: Genotype distribution was in Hardy-Weinberg equilibrium and differed between HIV+ patients and controls (P=0.030), irrespective of HBV or HCV coinfection. The p.126L variant, which was associated with MASP-2 levels <200ng/mL (OR=5.0 [95%CI=1.3-19.2] P=0.019), increased the susceptibility to HIV infection (OR=5.67 [95%CI=1.75-18.33], P=0.004) and to HIV+HBV+ status (OR=6.44 [95%CI=1.69-24.53, P=0.006). A similar association occurred with the ancient haplotype harboring this variant, AGCDV (OR=2.35 [95%CI=1.31-4.23], P=0.004). On the other hand, p.126L in addition to other variants associated with low MASP-2 levels-p.120G, p.377A and p.439H, presented a protective effect against AIDS (OR=0.25 [95%CI=0.08-0.80], P=0.020), independently of age, sex, hepatic function and viral load. MASP-2 serum levels were lower in HIV+ and HIV+HBV+ patients than in controls (P=0.0004). Among patients, MASP-2 levels were higher in patients with opportunistic diseases (P=0.001) and AIDS (P=0.004). MASP-2 levels correlated positively with MBL/MASP2-mediated C4 deposition (r=0.29, P=0.0002) and negatively with CD4+ cell counts (r=-0.21, P=0.018), being related to decreased CD4+ cell counts (OR=5.8 [95%CI=1.23-27.5, P=0.026). CONCLUSIONS: Genetically determined MASP-2 levels seem to have a two-edge effect in HIV and probably HCV/HBV coinfection, whereas low levels increase the susceptibility to infection, but on the other side protects against AIDS.