Bioimpedance spectroscopy characterization of Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS) peripheral blood mononuclear cells

Abstract:

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a disabling and chronic disease, importantly related to the current COVID-19 pandemic. Currently, there are no specific laboratory tests to directly diagnose ME/CFS. In this work, the use of impedance spectroscopy is studied as a potential technique for the diagnosis of ME/CFS. A specific device for the electrical characterization of peripheral blood mononuclear cells was designed and implemented.

Impedance spectroscopy measurements in the range from 1 Hz to 500 MHz were carried out after the osmotic stress of the samples with sodium chloride solution at 1M concentration. The evolution in time after the osmotic stress at two specific frequencies (1.36 kHz and 154 kHz) was analyzed.

The device showed its sensitivity to the presence of cells and the evolution of the osmotic processes. Higher values of impedance (around 15% for both the real and imaginary part) were measured at 1.36 kHz in ME/CFS patients compared to control samples. No significant difference was found between patient samples and control samples at 154 kHz. Results help to further understand the diagnosis of ME/CFS patients and the relation of their blood samples with bioimpedance measurements.

Source: Sara Martinez Rodriguez, Alberto Olmo Fernandez, Daniel Martin Fernandez, Isabel Martin-Garrido. Bioimpedance spectroscopy characterization of Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS) peripheral blood mononuclear cells. Biomedical Letters, Volume 9, Issue 2: 121-128. http://thesciencepublishers.com/biomed_lett/v9i2abstract6.html (Full text available as PDF file)

Bioimpedance spectroscopy characterization of osmotic stress processes in Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME-CFS) blood samples

Abstract:

Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/ CFS) is a disabling, chronic, multi-system and complex disease. Currently, there are no specific laboratory tests to directly [diagnose ME/CFS](https://www.cdc.gov/me-cfs/symptoms-diagnosis/diagnosis.html). In this work we study the use of impedance spectroscopy as a potential technique for the diagnosis of this disease. A specific device for the electrical characterization of peripheral blood mononuclear cells was designed and implemented.

Impedance spectroscopy measurements in the range from 1 Hz to 500 MHz were made after osmotic stress of the samples with sodium chloride solution 1M. The evolution in time after the osmotic stress at two specific frequencies (1.36 kHz and 154 kHz) was analysed. The device showed its sensitivity to the presence of cells and the evolution of the osmotic process. Higher values of impedance were measured for 1.36 kHz in ME/CFS patients compared to control samples. Results help to further understand the relation of bioimpedance measurements with ME/CFS samples physical properties and osmotic processes.

Source: Alberto Olmo Fernández, Sara Martínez Rodríguez, Daniel Martín Fernández, et al. Bioimpedance spectroscopy characterization of osmotic stress processes in Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME-CFS) blood samples. Authorea. July 11, 2023.
DOI: 10.22541/au.168909663.38868952/v1 https://www.authorea.com/doi/full/10.22541/au.168909663.38868952/v1 (Full text)

Complement Component C1q as a Potential Diagnostic Tool for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Subtyping

Abstract:

Background: Routine blood analytics are systematically used in the clinic to diagnose disease or confirm individuals’ healthy status. For myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a disease relying exclusively on clinical symptoms for its diagnosis, blood analytics only serve to rule out underlying conditions leading to exerting fatigue. However, studies evaluating complete and large blood datasets by combinatorial approaches to evidence ME/CFS condition or detect/identify case subgroups are still scarce.

Methods: This study used unbiased hierarchical cluster analysis of a large cohort of 250 carefully phenotyped female ME/CFS cases toward exploring this possibility.

Results: The results show three symptom-based clusters, classified as severe, moderate, and mild, presenting significant differences (p < 0.05) in five blood parameters. Unexpectedly the study also revealed high levels of circulating complement factor C1q in 107/250 (43%) of the participants, placing C1q as a key molecule to identify an ME/CFS subtype/subgroup with more apparent pain symptoms.

Conclusions: The results obtained have important implications for the research of ME/CFS etiology and, most likely, for the implementation of future diagnosis methods and treatments of ME/CFS in the clinic.

Source: Castro-Marrero J, Zacares M, Almenar-Pérez E, Alegre-Martín J, Oltra E. Complement Component C1q as a Potential Diagnostic Tool for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Subtyping. J Clin Med. 2021 Sep 15;10(18):4171. doi: 10.3390/jcm10184171. PMID: 34575280. https://pubmed.ncbi.nlm.nih.gov/34575280/

Gene profiling of patients with chronic fatigue syndrome/myalgic encephalomyelitis

Abstract:

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a multisystem disease, the pathogenesis of which remains undetermined. Following two microarray studies, we reported the differential expression of 88 human genes in patients with CFS; 85 of these genes were upregulated and 3 were downregulated.

The top functional categories of these 88 genes were hematologic disease and function, immunologic disease and function, cancer, cell death, immune response, and infection. Clustering of quantitative polymerase chain reaction data from CFS/ME patients revealed seven subtypes with distinct differences in Short Form (SF)-36 scores, clinical phenotypes, and severity. Gene signatures in each subtype implicate five human genes as possible targets for specific therapy.

Development of a diagnostic test for subtype status is now a priority. The possibility that these subtypes represent individual host responses to particular microbial infections is being investigated and may provide another route to specific therapies for CFS patients.

 

Source: Kerr JR. Gene profiling of patients with chronic fatigue syndrome/myalgic encephalomyelitis. Curr Rheumatol Rep. 2008 Dec;10(6):482-91. https://www.ncbi.nlm.nih.gov/pubmed/19007540

 

Complement activation in a model of chronic fatigue syndrome

Abstract:

BACKGROUND: A need exists to identify biological markers in chronic fatigue syndrome (CFS).

OBJECTIVE: To use an exercise and/or allergen challenge to induce the symptoms of CFS and to identify a biological marker that correlates with these symptoms.

METHODS: Patients with CFS (n = 32) and age-matched, normal control patients (n = 29) exercised for 20 minutes on a stationary bike at 70% of their predicted max work load (Watts). Patients from each group with positive skin test results were also challenged with intranasally administered relevant allergens. Symptoms were recorded for 2 weeks before and 1 week after each challenge, using 3 different instruments. Blood samples were taken before, and 0, 1, 6, and 24 hours after challenges. Levels of complement split products, cell-associated cytokines, and eosinophilic cationic protein were measured. Mean preexercise and postexercise symptom scores were evaluated for each group.

RESULTS: Exercise challenge induced significant increases of the complement split product C4a, but not C3a or C5a, at 6 hours after exercise only in the CFS group (P <.01), regardless of allergy status. Mean symptom scores were significantly increased after exercise through the use of a daily diary (P <.03) and a weekly diary (P <.01) for the CFS group only. Mean scores for the Multidimensional Fatigue Inventory categories “reduced activity” and “mental fatigue” were significantly increased in the CFS group only (P <.04 and P <.02, respectively).

CONCLUSIONS: Exercise challenge may be a valuable tool in the development of diagnostic criteria and tests for CFS. Establishment of a role for complement activation products as markers or participants in production of illness require further study.

 

Source: Sorensen B, Streib JE, Strand M, Make B, Giclas PC, Fleshner M, Jones JF. Complement activation in a model of chronic fatigue syndrome. J Allergy Clin Immunol. 2003 Aug;112(2):397-403. http://www.ncbi.nlm.nih.gov/pubmed/12897748

 

An investigation of sympathetic hypersensitivity in chronic fatigue syndrome

Abstract:

BACKGROUND: There are many theories, but the etiology of chronic fatigue syndrome (CFS) remains unknown. Diagnosticians have set guidelines to try to classify the condition, but its clinical definition is one of exclusion rather than defined by specific clinical testing. The primary goal of this investigation was to find a diagnostic key to define CFS. CFS patients and those diagnosed with the sympathetic hypersensitivity condition called fibromyalgia syndrome (FMS) exhibit identical brain single photon emission computerized tomography (SPECT) images. Therefore, this investigation was initiated to see if CFS patients also had denervation hypersensitivity of the sympathetic system.

METHODS: A standardized supersensitivity test was performed using an ocular instillation of two drops of 1.0% phenylephrine. Sixty-two subjects (29 CFS patients and 33 normals) participated in the study. Measurements of pupil size were recorded by pupil gauge and flash photography. A pupillary dilation of greater than 2.5 mm would suggest a sympathetic denervation hypersensitivity.

RESULTS: For all participants, a small, but statistically significant increase in pupil size was found (mean of 0.788 mm in normals and 0.931 mm in CFS patients). The change in pupil size in the CFS patients and controls showed substantial overlap and was not statistically significant (t = 0.83, p = 0.42, dF = 60).

CONCLUSION: In conclusion, the results suggest that a denervation hypersensitivity of the pupil does not occur in CFS patients. The use of 1.0% topical phenylephrine had no diagnostic value in detecting CSF patients vs. normals.

 

Source: Sendrowski DP, Buker EA, Gee SS. An investigation of sympathetic hypersensitivity in chronic fatigue syndrome. Optom Vis Sci. 1997 Aug;74(8):660-3. http://www.ncbi.nlm.nih.gov/pubmed/9323737