The European ME/CFS Biomarker Landscape project... (EUROMENE) (2016), Scheibenbogen et al

[MSEsperanza]

Scheibenbogen et al (2016), The European ME/CFS Biomarker Landscape project: an initiative of the European network EUROMENE , Journal of Translational Medicine, https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-017-1263-z#Sec4

pdf: The European ME/CFS Biomarker Landscape project: an initiative of the European network EUROMENE

Abstract

Myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) is a common and severe disease with a considerable social and economic impact. So far, the etiology is not known, and neither a diagnostic marker nor licensed treatments are available yet.[...]

To improve diagnosis and facilitate the analysis of clinical trials surrogate markers are urgently needed. As a first step for developing such biomarkers for clinical use a database of active biomarker research in Europe was established called the ME/CFS EUROMENE Biomarker Landscape project and the results are presented in this review.

Further we suggest strategies to improve biomarker development and encourage researchers to take these into consideration for designing and reporting biomarker studies.

From the discussion:

Further, immunological biomarkers reported mostly show alterations in subgroups only or with wide overlap to healthy control groups. Such heterogeneous results may be related to the fact that subgroups of ME/CFS patients exist with different immunological pathomechanisms. This concept is supported by the existence of clinical subgroups with heterogeneity in disease onset (infection- versus non-infection triggered), the variability of immune-associated symptoms, and the divergent response to B cell depletion therapy [43].

43= Fluge O, Risa K, Lunde S, Alme K, Rekeland IG, Sapkota D, Kristoffersen EK, Sorland K, Bruland O, Dahl O, Mella O. B‑lymphocyte depletion in myalgic encephalopathy/chronic fatigue syndrome. An open‑label phase ii study with rituximab maintenance treatment. PLoS ONE. 2015;10:e0129898

(I think this needs to be updated when the phase III results will be published.)

Similar to immunological markers, there is no single neurological or metabolic marker with sufficient specificity and sensitivity as a tool in ME/CFS diagnosis yet. However, recent studies analyzing multiple metabolites could show specific alterations in the majority of ME/CFS patients [37, 44–46] pointing to a probably common and specific metabolic profile.

Further, metabolic studies con-sistently revealed different gender-related patterns [37, 44, 46]. Thus, instead of searching single markers fitting for diagnosing all patients, multiplexed determinations of biomarkers analyzing pathways together with patient stratification, may be necessary to develop diagnostic assays with sufficient sensitivity and specificity [47].

Conclusions:

Heterogeneity of biomarker studies with different case definitions, low number of patients, lack of matched control groups, missing validation studies and potentially subgroup heterogeneity are possible reasons why no diagnostic biomarkers are available yet. Further, as result of the low amount of funding in CFS/ME research few and often small studies were performed so far. Therefore, strategies to improve the quality and to facilitate the comparability of biomarker studies are needed (summarized in Table 3).

This starts with well-defined patient cohorts using strict case definitions [47], standardized and quantitative symptom assessment for subgroup analyses, well-defined age- and sex-matched controls, and large enough cohort size and a predefined hypothesis to power the statistical analysis. Detailed description of cohorts, assays performed and results achieved are important to facilitate confirmation studies.

Reproducing results in cohorts from different countries, developing Standard Operating Procedures (SOPs) for assays, and multi-center studies are important steps for evaluating the suitability of biomarkers of interest as diagnostic markers. The building of translational networks of clinical and basic research groups like promoted in EUROMENE is an important first step to achieve such goals. Finally, to promote research it is crucial to increase funding for ME/CFS which is currently still far below the budget funds for most other serious diseases in both the EU and the US funding agencies, such as the National Institutes of Health (NIH) [48].

(Couldn't find this paper on our forum yet--please alert me in case I've overlooked a thread.
Will add tags later).