Búsqueda de biomarcadores de daño renal en pacientes con lupus eritematoso sistémico a través un abordaje metabolómico no dirigido
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2023
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Ediciones Universidad Simón Bolívar
Facultad de Ciencias Básicas y Biomédicas
Facultad de Ciencias Básicas y Biomédicas
Resumen
El lupus eritematoso sistémico (LES) es la enfermedad autoinmune multiorgánica prototípica, que se relaciona con una alta morbilidad y muerte temprana de personas en edad productiva. La nefritis lúpica (NL) es una de las mayores complicaciones del LES ya que se presenta en el 50% de los pacientes diagnosticados con esta enfermedad. El diagnóstico y la clasificación de la NL se basa en los resultados histopatológicos de la biopsia renal, sin embargo, a pesar de ser el estándar de oro, la biopsia sigue siendo un método altamente invasivo y poco práctico para el monitoreo en tiempo real del estadio de la NL. El presente estudio se diseñó para encontrar nuevos biomarcadores en muestras de orina que pudieran diferenciar entre los pacientes con LES y aquellos con NL utilizando un método de metabolómica no dirigida basado en cromatografía líquida acoplada a espectrometría de masas (CL-QTOF-EM). Se recolectaron muestras de orina de 50 sujetos que acudieron a consulta externa de nefrología en la Clínica de la Costa, incluyendo controles sanos, sujetos con LES y con LN clase III y clase IV. Las muestras se analizaron posteriormente mediante LC-QTOF-MS, por medio de lo cual se identificaron 38 metabolitos con diferencia significativa entre los grupos de LES y de NL. Luego, estos metabolitos se correlacionaron a vías metabólicas que podrían estar implicadas en la progresión del LN. Adicionalmente, tres metabolitos, el monopalmitin, el ácido glutámico y el ácido glicocólico, demostraron un alto poder predictivo como posibles biomarcadores para el diagnóstico de la NL. Estos hallazgos no solo proporcionan nuevos conocimientos sobre la firma metabólica urinaria del SLE y la NL; también proponen una alternativa diagnostica para la discriminación de la NL en sujetos con LES.
Systemic lupus erythematous (SLE) is the prototypical multiorgan autoimmune disease, which is associated with high morbidity and early death of young and productive people. Lupus nephritis (LN) is one of the major complications of SLE since it occurs in 50% of patients diagnosed with this disease. The diagnosis and classification of the LN is based on the histopathological results of the renal biopsy, however, despite being the gold standard, the biopsy is a highly invasive method that is impractical for real-time monitoring of LN progression. The present study was designed to find new signatures in urine samples that could differentiate between patients with SLE and those with NL using non-targeted metabolomics based on liquid chromatography coupled to mass spectrometry (LC-QTOF-MS). Urine samples were collected from 50 subjects who attended an outpatient nephrology consult at Clínica de la Costa, including healthy controls, subjects with SLE and LN class III and class IV. The samples were subsequently analysed through LC-QTOF-MS, which identified 38 metabolites with a significant difference between the SLE and LN groups. These metabolites were then correlated to metabolic pathways that could be involved in the progression of the LN. In addition, three metabolites, monopalmitin, glutamic acid and glychocolic acid, demonstrated high predictive power as possible biomarkers for the diagnosis of NL. These findings not only provide new knowledge about the urinary metabolic profiles of the SLE and the NL; they also propose a diagnostic alternative for the discrimination of LN in subjects with SLE.
Systemic lupus erythematous (SLE) is the prototypical multiorgan autoimmune disease, which is associated with high morbidity and early death of young and productive people. Lupus nephritis (LN) is one of the major complications of SLE since it occurs in 50% of patients diagnosed with this disease. The diagnosis and classification of the LN is based on the histopathological results of the renal biopsy, however, despite being the gold standard, the biopsy is a highly invasive method that is impractical for real-time monitoring of LN progression. The present study was designed to find new signatures in urine samples that could differentiate between patients with SLE and those with NL using non-targeted metabolomics based on liquid chromatography coupled to mass spectrometry (LC-QTOF-MS). Urine samples were collected from 50 subjects who attended an outpatient nephrology consult at Clínica de la Costa, including healthy controls, subjects with SLE and LN class III and class IV. The samples were subsequently analysed through LC-QTOF-MS, which identified 38 metabolites with a significant difference between the SLE and LN groups. These metabolites were then correlated to metabolic pathways that could be involved in the progression of the LN. In addition, three metabolites, monopalmitin, glutamic acid and glychocolic acid, demonstrated high predictive power as possible biomarkers for the diagnosis of NL. These findings not only provide new knowledge about the urinary metabolic profiles of the SLE and the NL; they also propose a diagnostic alternative for the discrimination of LN in subjects with SLE.
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Lupus eritematoso sistémico, Nefritis lúpica, Metabolómica, Espectrometría de masas, Cromatografía líquida, Biomarcadores, Systemic Lupus Erythematous, Lupus Nephritis, Metabolomics, Mass Spectrometry, Liquid Chromatography, Biomarkers
