Inclusion of family members without ME/CFS in research studies promotes discovery of biomarkers specific for ME/CFS, 2020, Tokunaga et al

Andy · Jun 23, 2020

BACKGROUND: The search for a biomarker specific for ME/CFS (myalgic encephalomyelitis/chronic fatigue syndrome) has been long, arduous and, to date, unsuccessful. Researchers need to consider their expenditures on each new candidate biomarker. In a previous study of antibody-dependent cell-mediated cytotoxicity (ADCC) by natural killer lymphocytes, we found lower ADCC for ME/CFS patients vs. unrelated donors but ruled against low ADCC as a biomarker because of similar ADCC for patients vs. their family members without ME/CFS.

OBJECTIVE: We applied inclusion of family members without ME/CFS, from families with multiple CFS patients, as a second non-ME/CFS control group in order to re-examine inflammation in ME/CFS. METHOD:Total and CD16A-positive ‘non-classical’ anti-inflammatory monocytes were monitored.

RESULTS: Non-classical monocytes were elevated for patients vs. unrelated healthy donors but these differences were insignificant between patients vs. unaffected family members.

CONCLUSIONS: Inclusion of family members ruled against biomarker considerations for the monocytes characterized. These pilot findings for the non-classical monocytes are novel in the field of ME/CFS. We recommend that occupational therapists advocate and explain to family members without ME/CFS the need for the family members’ participation as a second set of controls in pilot studies to rapidly eliminate false biomarkers, optimize patient participation, and save researchers’ labor.
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Paywall, https://content.iospress.com/articles/work/wor203177
Sci hub, https://sci-hub.tw/10.3233/WOR-203177

Hoopoe · Jun 28, 2020

For those interested in biomarker discovery and quality control, this seems interesting. Maybe also of interest to @Jonathan Edwards. I'm trying to summarize:

Family members have close genetic backgrounds and often similar lifestyles to the patients, and can optimize discovery of specific biomarkers by serving as maximally matched controls. In this report, we searched for a biomarker using 3 families each with 2 ME/CFS patients. The idea was to screen for a new biomarker of infection and/or inflammation that would be worthy of additional research.
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We observed elevation of the non-classical monocytes in patients vs. unrelated donors (P< 0.05) but this difference is unsuitable as a biomarker because there was little difference between patients compared to their non-ME/CFS family members. The results underscore the value of the unaffected family members to prevent false positive conclusions concerning biomarkers.
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They were 55% higher. Non-classical monocytes are described as anti-inflammatory and being involved in maintenance of vascular homeostasis.

We also found merit for inclusion of unaffected family members in a pilot study of antibody-dependent (ADCC) mediated by NK cells in ME/CFS (manuscript in preparation). The inclusion of unaffected family indicated that low ADCC is unsuitable as a biomarker for ME/CFS but could be a risk factor for ME/CFS.
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I also think that families with multiple cases of ME/CFS could be very valuable for research for the reasons mentioned above. Not just to prevent false positives in biomarker research but also to identify the genetic and environmental risk factors.

Dolphin · Nov 24, 2022

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Inclusion of family members without ME/CFS in research studies promotes discovery of biomarkers specific for ME/CFS, 2020, Tokunaga et al

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Inclusion of family members without ME/CFS in research studies promotes discovery of biomarkers specific for ME/CFS, 2020, Tokunaga et al

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