Medicina

Multiple sclerosis (MS) is a demyelinating and neurodegenerative disease of the central nervous system. It affects young people, and a considerable percentage of patients need the help of a wheelchair in 15 years of evolution. Currently, there is not a specific technique for the diagnosis of MS. The detection of oligoclonal IgG bands (OIgGBs) is the most sensitive assay for it, but it is not standardizable, only reference laboratories develop it, and uses cerebrospinal fluid. To obtain this sample, a lumbar puncture is necessary, an invasive proceeding with important side effects. It is important to develop and implement standard assays to obtain a rapid diagnosis because the earlier the treatment, the better the evolution of the disease. There are numerous modifying disease therapies, which delay the progression of the disease, but they have important side effects, and a considerable percentage of patients give up the treatment. In addition, around 40% of MS patients do not respond to the therapy and the disease progresses. Numerous researches have been focused on the characterization of predictive biomarkers of response to treatment, in order to help physicians to decide when to change to a second-line treatment, and then the best therapeutic option. Here, we review the new biomarkers for the diagnosis and response to treatment in MS. We draw attention in a new assay, the detection of serum IgM to phosphatidylcholine, that showed a similar sensitivity as OIgGBs and predicts the response to disease modifying treatments.

Background: Antibodies to lipids are part of the first line of defense against microorganisms and regulate the pro/anti-inflammatory balance. Viruses modulate cellular lipid metabolism to enhance their replication, and some of these metabolites are proinflammatory. We hypothesized that antibodies to lipids would play a main role of in the defense against SARS-CoV-2 and thus, they would also avoid the hyperinflammation, a main problem in severe condition patients. Methods: Serum samples from COVID-19 patients with mild and severe course, and control group were included. IgG and IgM to different glycerophospholipids and sphingolipids were analyzed using a high-sensitive ELISA developed in our laboratory. A lipidomic approach for studying lipid metabolism was performed using ultra-high performance liquid chromatography coupled to electrospray ionization and quadrupole time-of-flight mass spectrometry (UHPLC-ESI-QTOF-MS). Results: Mild and severe COVID-19 patients had higher levels of IgM to glycerophosphocholines than control group. Mild COVID-19 patients showed higher levels of IgM to glycerophosphoinositol, glycerophosphoserine and sulfatides than control group and mild cases. 82.5% of mild COVID-19 patients showed IgM to glycerophosphoinositol or glycerophosphocholines plus sulfatides or glycerophosphoserines. Only 35% of severe cases and 27.5% of control group were positive for IgM to these lipids. Lipidomic analysis identify a total of 196 lipids, including 172 glycerophospholipids and 24 sphingomyelins. Increased levels of lipid subclasses belonging to lysoglycerophospholipids, ether and/or vinyl-ether-linked glycerophospholipids, and sphingomyelins were observed in severe COVID-19 patients, when compared with those of mild cases and control group. Conclusion: Antibodies to lipids are essential for defense against SARS-CoV-2. Patients with low levels of anti-lipid antibodies have an elevated inflammatory response mediated by lysoglycerophospholipids. These findings provide novel prognostic biomarkers and therapeutic targets.