Thermal Liquid Biopsy (TLB) of Blood Plasma as a Potential Tool to Help in the Early Diagnosis of Multiple Sclerosis

Abstract

Background: Multiple sclerosis (MS) is frequently characterized by a variety of clinical signs, often exhibiting little specificity. The diagnosis requires a combination of medical observations and instrumental tests, and any support for its objective assessment is helpful. Objective: Herein, we describe the application of thermal liquid biopsy (TLB) of blood plasma samples, a methodology for predicting the occurrence of MS with a noninvasive, quick blood test. Methods: TLB allows one to define an index (TLB score), which provides information about overall real-time alterations in plasma proteome that may be indicative of MS. Results: This pilot study, based on 85 subjects (45 MS patients and 40 controls), showed good performance indexes (sensitivity and specificity both around 70%). The diagnostic methods better discriminate between early stage and low-burden MS patients, and it is not influenced by gender, age, or assumption of therapeutic drugs. TLB is more accurate for patients having low disability level (≤ 3.0, measured by the expanded disability status scale, EDSS) and a relapsing–remitting diagnosis. Conclusion: Our results suggest that TLB can be applied to MS, especially in an initial phase of the disease when diagnosis is difficult and yet more important (in such cases, accuracy of prediction is close to 80%), as well as in personalized patient periodic monitoring. The next step will be determining its utility in differentiating between MS and other disorders, in particular in inflammatory diseases.

Calorimetric Markers for Detection and Monitoring of Multiple Myeloma

“…The position and amplitude of the resolved transitions as well as the weighted average center (T FM ) of plasma/sera thermograms were shown to be rather constant for serum derived from healthy individuals [ 1 , 2 , 4 ]. These thermodynamic parameters were shown to change significantly for a number of diseases [ 1 , 4 , 9 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ], and especially for various types of cancer—breast [ 20 , 21 , 22 , 23 ], pancreatic [ 24 ], cervical [ 25 , 26 , 27 ], lung [ 28 , 29 , 30 , 31 , 32 ], brain [ 6 , 31 , 33 ], colorectal [ 18 ], gastric adenocarcinoma [ 34 ], melanoma [ 35 , 36 , 37 ], multiple myeloma (MM) [ 5 , 38 , 39 , 40 , 41 , 42 , 43 ], chronic lymphocytic leukemia and acute myeloid leukemia [ 44 ]—and can therefore be used to stratify DSC data into different disease-related groups.…”

Bowel Preparation for Colonoscopy Changes Serum Composition as Detected by Thermal Liquid Biopsy and Fluorescence Spectroscopy

“…We have developed a multiparametric phenomenological model in which the TLB serum thermogram is deconvoluted into six individual transitions, modeling each individual transition using the logistic peak or Hubbert function [ 13 , 15 ]. This model has been successfully applied in the analysis of serum samples from patients with melanoma, gastric and lung cancer, pancreatic cysts, and multiple sclerosis [ 13 , 14 , 15 , 16 , 17 ]. The primary parameters obtained directly from the thermogram deconvolution (center temperature, height, and width of each individual transition) were combined to define a new final set of 11 parameters, more convenient for extracting and summarizing the essential geometric features of the thermogram.…”

“…Other groups have applied DSC to serum/plasma samples associated to inflammation and tumor diseases [ 8 , 9 , 10 , 11 , 12 ]. In our group, we have been working on the development of thermal liquid biopsy (TLB) as a diagnostic technique, applying it to different pathologies such as gastric adenocarcinoma [ 13 ], melanoma [ 14 ], lung cancer [ 15 ], pancreatic cyst [ 16 ], and multiple sclerosis [ 17 ]. Our goal is to propose an additional test based on TLB for reducing the number of colonoscopy unnecessary arising from FIT(+).…”

ATR-FTIR spectroscopy of plasma supported by multivariate analysis discriminates multiple sclerosis disease

“…To detect and quantify biological materials such as proteins, carbohydrates, nucleic acids, lipids, metabolites, as well as searching for disease-specific biomarkers, high sensitivity biophysical/analytical techniques are available. These methods include differential scanning calorimetry 14 – 16 , mass spectrometry 17 , nuclear magnetic resonance (NMR) 18 , 19 and infrared (IR) spectroscopy 20 . In particular, vibrational spectroscopy, in the mid-IR range, is largely expanding in the biomedical area to investigate complex biological fluids, such as blood and blood derivatives (plasma and serum), CSF, saliva, as well as cells and tissues 20 – 24 .…”