RESUMO
Multiple sclerosis (MS) is an autoimmune disease characterized by demyelination and neuroinflammation, often accompanied by cognitive impairment. This study aims (1) to investigate the potential of glatiramer acetate (GA) as a therapy for preventing cognitive decline in patients with MS (pwMS) by modulating oxidative stress (OS) and (2) to seek out the differences in cognition between pwMS in a cohort exhibiting good clinical evolution and control subjects (CS). An exploratory, prospective, multicentre, cross-sectional case-control study was conducted, involving three groups at a 1:1:1 ratio-41 GA-treated pwMS, 42 untreated pwMS, and 42 CS. The participants performed a neuropsychological battery and underwent venepuncture for blood sampling. The inclusion criteria required an Expanded Disability Status Scale score of ≤3.0 and a minimum of 5 years of MS disease. Concerning cognition, the CS had a better performance than the pwMS (p = <0.0001), and between those treated and untreated with GA, no statistically significant differences were found. Regarding oxidation, no statistically significant differences were detected. Upon categorizing the pwMS into cognitively impaired and cognitively preserved groups, the lactate was elevated in the pwMS with cognitive preservation (p = 0.038). The pwMS exhibited a worse cognitive performance than the CS. The pwMS treated with GA did not show an improvement in oxidation. Lactate emerged as a potential biomarker for cognitive preservation.
RESUMO
La determinación de Subpoblaciones Linfocitarias Humanas (SLH) por Citometría de Flujo, Linfocitos CD3+ (LT), LTCD4+, LTCD8+ y la relación LTCD4+/LTCD8+, permiten monitorear pacientes infectados con virus de la inmunodeficiencia humana (VIH), los cuales son comparados con Valores de Referencia (VR). A su vez los VR informados por la bibliografía son variables debido a la falta de validación analítica y partición estadística de los datos de VR, entre otros. En este trabajo, utilizando un ensayo validado (ISO15189), se establecieron VR para SLH con criterios estadísticos de partición en individuos con serología negativa para VIH (397 mujeres (F) y 279 varones (M), edad: 17-83 años). Las SLH fueron medidas en un Citómetro de Flujo (Coulter Epics XL-MCL). Los datos fueron procesados empleando como criterio estadístico de partición el algoritmo de Martin Gellerstedt (AMG). Del análisis estadístico y del AMG se determinó la partición de los datos en 6 subpoblaciones definidas por edad (intervalo de años) y género (F y M): grupos I y IV: 17-35 (F y M); grupos II y V: 36-50 (F y M); y grupos III y VI: >50 años (F y M). Para los 6 grupos se definieron VR de linfocitos totales, LT, LTCD4+, LTCD8+ y LTCD4+/LTCD8+. Para cada límite inferior y superior de VR se estableció el intervalo de confianza al 90%. En conclusión, este estudio permitió establecer VR para SLH en un ensayo validado empleando un criterio estadístico de partición, lo cual permitiría incrementar la confiabilidad de los resultados y uniformar a nivel internacional los VR en SLH en diferentes poblaciones.
The determination of Human Lymphocyte Subpopulations (HLS) including Lymphocytes CD3+ (LT), LTCD4+, LTCD8+ and LTCD4+/LTCD8+ ratio by flow cytometry, makes it possible to monitor patients infected who HIV, which are compared against reference values (RV). However, RV reported by the international bibliography are variable due to the absence of two main factors: analytical validation procedures and partitioning statistical criteria. This study, using a validated method (ISO15189), RV were established for HLS in individuals with negative serology for HIV (397 females (F) and 279 males (M), age: 17-83 years) applying partitioning statistical criteria. The values of HLS were obtained by flow cytometry (Coulter Epics XL-MCL). The data were processed using partitioning statistical criteria based on Martin Gellerstedt's algorithm (MGA). From the statistical analysis and MGA the partition of the data was determined in 6 subpopulations defined by age (interval of years) and gender (F and M): groups I and IV: 17-35 (F and M); groups II and V: 36-50 (F and M); and groups III and VI: >50 years (F and M). Hence, RV of total lymphocytes, LT, LTCD4+, LTCD8+ and LTCD4+/LTCD8+ ratio were defined. For each limit (lower and upper) of reference values, the 90% confidence interval was determined. In conclusion, this study allowed establishing RV for HLS in a validated method using a partitioning statistical criterion, which would allow increasing the assurance results and establishing an international criterion for reference values in HLS in different populations.