Inclusion of family members without ME/CFS in research studies promotes discovery of biomarkers specific for ME/CFS

Abstract

BACKGROUND:The search for a biomarker specific for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) 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.

Biomarkers for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): a systematic review

“…The study and participant characteristics as well as findings of each article is summarised in Additional File 2 . In total, 98 out of 101 included publications were observational case–control studies [ 15 – 112 ].Two of these studies also included non-ME/CFS affected blood relatives in addition to HC [ 102 , 109 ]. One publication was an observational twin study [ 113 ], and the remaining two publications were prospective longitudinal linked panel studies [ 114 , 115 ].…”

“…One study recruited patients diagnosed with the ICC [ 25 ], and another study recruited patients diagnosed with IOMC [ 34 ]. A combination of FC and CCC was used to diagnose patients in 19 studies [ 16 , 18 , 26 , 27 , 30 , 48 , 51 , 54 , 56 , 60 , 70 , 72 , 74 – 77 , 85 , 90 , 97 ], a combination of FC and ICC was used to select patients in three studies [ 55 , 106 , 109 ], and a combination of CCC and ICC was used to select patients in one study [ 29 ]. A combination of the FC and IOMC was used in one study [ 41 ].…”

“…Thirty studies investigated immune cell function changes in ME/CFS patients compared with HC (Additional File 2 , Table S2) [ 22 , 26 , 33 , 36 , 37 , 45 , 46 , 48 – 51 , 54 , 56 , 61 , 62 , 64 , 65 , 72 , 84 , 91 , 97 , 99 , 102 , 104 , 107 , 109 , 110 , 114 , 115 ]. Five of the studies reported reduced NKCC in ME/CFS patients compared with HC [ 37 , 65 , 67 , 102 , 114 ].…”

“…Higher non-classical monocytes were found in ME/CFS patients compared with HC [ 109 ]. There was no significant difference, however, between patients and non-affected family members [ 109 ].…”

“…Higher non-classical monocytes were found in ME/CFS patients compared with HC [ 109 ]. There was no significant difference, however, between patients and non-affected family members [ 109 ]. Sung et al also examined differences between ME/CFS patients, related family members and HC [ 102 ].…”