Metabolites and metabolic pathways associated with rheumatoid arthritis and systemic lupus erythematosus.

Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are chronic autoimmune diseases that result from the combined influence of genetic and environmental factors that promotes the loss of tolerance to cellular components. The complexity of these diseases converts them into a major challenge at the diagnostic and treatment level. Therefore, it is convenient to implement the use of tools for a better understanding of the physiopathology of these diseases to propose reliable biomarkers. The "omics" disciplines like metabolomics and lipidomics allow to study RA and SLE in a higher degree of detail since they evaluate the metabolites and metabolic pathways involved in disease pathogenesis. This review has compiled the information of metabolomics and lipidomics studies where samples obtained from RA and SLE patients were evaluated to find the metabolites and pathways differences between patients and healthy controls. In both diseases, there is a decrease in several amino acids and oxidative stress-related metabolites like glutathione. These findings may be useful for functional metabolomics studies aiming to reprogram the metabolism in a disease setting to recover normal immune cell homeostasis and function.

Blood-brain barrier disruption and neuroinflammation as pathophysiological mechanisms of the diffuse manifestations of neuropsychiatric systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease that can involve nervous system commitment known as neuropsychiatric systemic lupus erythematosus (NPSLE). The diagnostic of NPSLE is complex because the symptoms range from focal symptoms (e.g., strokes, thrombotic events) to diffuse disorders affecting cognition, mood and level of consciousness (e.g. acute confusional state, psychosis). Both type of manifestations of NPSLE differ in their pathological mechanisms. The focus of this review will be on the mechanisms that lead to the blood-brain barrier (BBB) disruption and to the neuroinflammation related with the diffuse manifestations of NPSLE.

Identification of Levels of Serum Amyloid A and Apolipoprotein A1 in Serum Proteomic Analysis of Neuropsychiatric Systemic Lupus Erythematosus Patients.

Neuropsychiatric Systemic Lupus Erythematosus (NPSLE) has multiple pathogenic mechanisms that cause diverse manifestations and whose diagnosis is challenging because of the absence of appropriate diagnostic tests. In the present study the application of proteomics using two-dimensional electrophoresis (2D) and mass spectrometry (MS) allowed the comparison of the protein profile of the serum low and high abundance protein fractions of NPSLE patients (NPSLE group) and SLE without neuropsychiatric syndromes (SLE group), Neuropsychiatric syndromes not associated with SLE (NPnoSLE groups), and healthy controls (CTRL group). The gels obtained were digitalized and analyzed with the PDQuest software. The statistical analysis of the spots was performed using the nonparametric Kruskal Wallis and Dunn's multiple comparison tests. Two spots showed significant differences and were identified by MS. Spot 4009 was significantly lower in NPSLE with regard to NPnoSLE (p= 0,004) and was identified as apolipoprotein A1 (APOA1) (score 809-1132). Spot 8001 was significantly higher in NPSLE regarding CTRL and NPnoSLE (p= 0,01 y 0,03, respectively) and was identified as serum amyloid A (SAA) (score 725-2488). The proinflammatory high density lipoproteins (HDL) have been described in SLE. In this HDL the decrease of APOA1 is followed by an increase in SAA. This altered level of both proteins may be related to the inflammatory state that is characteristic of an autoimmune disease like SLE, but this is not specific for NPSLE.