Developing a Blood Cell‐Based Diagnostic Test for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Using Peripheral Blood Mononuclear Cells

Xu, Jiabao; Lodge, Tiffany; Kingdon, Caroline; Strong, James W. L.; Maclennan, John; Lacerda, Eliana; Kujawski, Slawomir; Zalewski, Pawel; Huang, Wei E.; Morten, Karl J.

doi:10.1002/advs.202302146

Cited by 5 publications

(3 citation statements)

References 66 publications

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“…The multi-marker environment with complex interlinks requires an AI-based toolkit for decision support. The resulting outcomes when stacking various AI-based decision machines have yet to be determined in the case of ME/CFS [see ( 44 ) for a novel stacking approach]. Clearly, the inflammatome–immunome interaction is a criterion that complements machine-learning-based AI systems as described in ( 45 ).…”

Section: Discussionmentioning

confidence: 99%

Exploring the joint potential of inflammation, immunity, and receptor-based biomarkers for evaluating ME/CFS progression

Berkis,

Svirskis,

Krumina

et al. 2023

Front. Immunol.

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BackgroundMyalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating chronic condition with no identified diagnostic biomarkers to date. Its prevalence is as high as 0.89% according to metastudies, with a quarter of patients bed- or home-bound, which presents a serious public health challenge. Investigations into the inflammation–immunity axis is encouraged by links to outbreaks and disease waves. Recently, the research of our group revealed that antibodies to beta2-adrenergic (anti-β2AdR) and muscarinic acetylcholine (anti-M4) receptors demonstrate sensitivity to the progression of ME/CFS. The purpose of this study is to investigate the joint potential of inflammatome—characterized by interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-2, IL-21, Il-23, IL-6, IL-17A, Activin-B, immunome (IgG1, IgG2, IgG3, IgG4, IgM, and IgA), and receptor-based biomarkers (anti-M3, anti-M4, and anti-β2AdR)—for evaluating ME/CFS progression, and to identify an optimal selection for future validation in prospective clinical studies.MethodsA dataset was used originating from 188 individuals, namely, 54 healthy controls, 30 patients with a “mild” condition, 73 patients with a “moderate” condition, and 31 patients with a “severe” condition, clinically assessed by Fukuda/CDC 1994 and international consensus criteria. Inflammatome, immunome, and receptor-based biomarkers were determined in blood plasma via ELISA and multiplex methods. Statistical analysis was done via correlation analysis, principal component analysis, linear discriminant analysis, and random forest classification; inter-group differences were tested via nonparametric Kruskal–Wallis H test followed by the two-stage linear step-up procedure of Benjamini, Krieger, and Yekutieli, and via Mann–Whitney U test.ResultsThe association between inflammatome and immunome markers is broader and stronger (coupling) in the severe group. Principal component factoring separates components associated with inflammatome, immunome, and receptor biomarkers. Random forest modeling demonstrates an excellent accuracy of over 90% for splitting healthy/with condition groups, and 45% for splitting healthy/severity groups. Classifiers with the highest potential are anti-β2AdR, anti-M4, IgG4, IL-2, and IL-6.DiscussionThe association between inflammatome and immunome markers is a candidate for controlled clinical study of ME/CFS progression markers that could be used for treatment individualization. Thus, the coupling effects between inflammation and immunity are potentially beneficial for the identification of prognostic factors in the context of ME/CFS progression mechanism studies.

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Section: Discussionmentioning

confidence: 99%

Exploring the joint potential of inflammation, immunity, and receptor-based biomarkers for evaluating ME/CFS progression

Berkis,

Svirskis,

Krumina

et al. 2023

Front. Immunol.

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“…In addition, he has developed a novel Raman spectroscopy approach which examines peripheral blood mononuclear cells (PBMCs), and diagnoses ME/CFS with 90% accuracy based on impaired cellular bioenergetics and dysfunctional mitochondrial profiles. 21 These tests provide diagnostic possibilities and may point to metabolites and metabolic pathways that play a role in the disease pathology.…”

Section: Organ-specific Syndromesmentioning

confidence: 99%

Long COVID and post‐acute sequelae of SARS‐CoV‐2 pathogenesis and treatment: A Keystone Symposia report

Durstenfeld,

Weiman,

Holtzman

et al. 2024

Annals of the New York Academy of Sciences

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In 2023, the Keystone Symposia held the first international scientific conference convening research leaders investigating the pathology of post‐acute sequelae of COVID‐19 (PASC) or Long COVID, a growing and urgent public health priority. In this report, we present insights from the talks and workshops presented during this meeting and highlight key themes regarding what researchers have discovered regarding the underlying biology of PASC and directions toward future treatment. Several themes have emerged in the biology, with inflammation and other immune alterations being the most common focus, potentially related to viral persistence, latent virus reactivation, and/or tissue damage and dysfunction, especially of the endothelium, nervous system, and mitochondria. In order to develop safe and effective treatments for people with PASC, critical next steps should focus on the replication of major findings regarding potential mechanisms, disentangling pathogenic mechanisms from downstream effects, development of cellular and animal models, mechanism‐focused randomized, placebo‐controlled trials, and closer collaboration between people with lived experience, scientists, and other stakeholders. Ultimately, by learning from other post‐infectious syndromes, the knowledge gained may help not only those with PASC/Long COVID, but also those with other post‐infectious syndromes.

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“…Xu et al [ 52 ] proposed a new potential biomarker, phenylalanine, for the diagnosis of ME/CFS using PBMCs and single-cell Raman spectroscopy. More recently, the same group of authors developed a more powerful single-cell Raman platform, combined with artificial intelligence, to analyze blood cells from 98 human subjects, comprising 61 ME/CFS patients with varying disease severity and 37 healthy and MS patients as disease control [ 53 ]. The results demonstrated that Raman profiles of blood cells can accurately distinguish between healthy individuals, disease controls, and ME/CFS patients with high accuracy (91%).…”

Section: Raman Micro-spectroscopy Unveiled: Illuminating Metabolism A...mentioning

confidence: 99%

Raman micro-spectroscopy as a tool to study immunometabolism

Xu,

Morten

2024

Biochemical Society Transactions

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In the past two decades, immunometabolism has emerged as a crucial field, unraveling the intricate molecular connections between cellular metabolism and immune function across various cell types, tissues, and diseases. This review explores the insights gained from studies using the emerging technology, Raman micro-spectroscopy, to investigate immunometabolism. Raman micro-spectroscopy provides an exciting opportunity to directly study metabolism at the single cell level where it can be combined with other Raman-based technologies and platforms such as single cell RNA sequencing. The review showcases applications of Raman micro-spectroscopy to study the immune system including cell identification, activation, and autoimmune disease diagnosis, offering a rapid, label-free, and minimally invasive analytical approach. The review spotlights three promising Raman technologies, Raman-activated cell sorting, Raman stable isotope probing, and Raman imaging. The synergy of Raman technologies with machine learning is poised to enhance the understanding of complex Raman phenotypes, enabling biomarker discovery and comprehensive investigations in immunometabolism. The review encourages further exploration of these evolving technologies in the rapidly advancing field of immunometabolism.

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Developing a Blood Cell‐Based Diagnostic Test for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Using Peripheral Blood Mononuclear Cells

Cited by 5 publications

References 66 publications

Exploring the joint potential of inflammation, immunity, and receptor-based biomarkers for evaluating ME/CFS progression

Exploring the joint potential of inflammation, immunity, and receptor-based biomarkers for evaluating ME/CFS progression

Long COVID and post‐acute sequelae of SARS‐CoV‐2 pathogenesis and treatment: A Keystone Symposia report

Raman micro-spectroscopy as a tool to study immunometabolism

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