Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a frequent and severe chronic disease drastically impairing life quality. The underlying pathomechanism is incompletely understood yet but there is convincing evidence that in at least a subset of patients ME/CFS has an autoimmune etiology. In this review, we will discuss current autoimmune aspects for ME/CFS. Immune dysregulation in ME/CFS has been frequently described including changes in cytokine profiles and immunoglobulin levels, T- and B-cell phenotype and a decrease of natural killer cell cytotoxicity. Moreover, autoantibodies against various antigens including neurotransmitter receptors have been recently identified in ME/CFS individuals by several groups. Consistently, clinical trials from Norway have shown that B-cell depletion with rituximab results in clinical benefits in about half of ME/CFS patients. Furthermore, recent studies have provided evidence for severe metabolic disturbances presumably mediated by serum autoantibodies in ME/CFS. Therefore, further efforts are required to delineate the role of autoantibodies in the onset and pathomechanisms of ME/CFS in order to better understand and properly treat this disease.

Designed by a group of ME/CFS researchers and health professionals, the European Network on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (EUROMENE) has received funding from the European Cooperation in Science and Technology (COST)—COST action 15111—from 2016 to 2020. The main goal of the Cost Action was to assess the existing knowledge and experience on health care delivery for people with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) in European countries, and to enhance coordinated research and health care provision in this field. We report our findings and make recommendations for clinical diagnosis, health services and care for people with ME/CFS in Europe, as prepared by the group of clinicians and researchers from 22 countries and 55 European health professionals and researchers, who have been informed by people with ME/CFS.

BackgroundChronic Fatigue Syndrome (CFS) is a debilitating neuro-immune disorder of unknown etiology diagnosed by an array of clinical manifestations. Although several immunological abnormalities have been described in CFS, their heterogeneity has limited diagnostic applicability.MethodsImmunological features of CFS were screened in 22 CFS diagnosed individuals fulfilling Fukuda criteria and 30 control healthy individuals. Peripheral blood T, B and NK cell function and phenotype were analyzed by flow cytometry in both groups.ResultsCFS diagnosed individuals showed similar absolute numbers of T, B and NK cells, with minor differences in the percentage of CD4+ and CD8+ T cells. B cells showed similar subset frequencies and proliferative responses between groups. Conversely, significant differences were observed in T cell subsets. CFS individuals showed increased levels of T regulatory cells (CD25+/FOXP3+) CD4 T cells, and lower proliferative responses in vitro and in vivo. Moreover, CD8 T cells from the CFS group showed significantly lower activation and frequency of effector memory cells. No clear signs of T-cell immunosenescence were observed. NK cells from CFS individuals displayed higher expression of NKp46 and CD69 but lower expression of CD25 in all NK subsets defined. Overall, T cell and NK cell features clearly clustered CFS individuals.ConclusionsOur findings suggest that alterations in T-cell phenotype and proliferative response along with the specific signature of NK cell phenotype may be useful to identify CFS individuals. The striking down modulation of T cell mediated immunity may help to understand intercurrent viral infections in CFS.

This review explores the current evidence on benefits and harms of therapeutic interventions in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) and makes recommendations. CFS/ME is a complex, multi‐system, chronic medical condition whose pathophysiology remains unknown. No established diagnostic tests exist nor are any FDA‐approved drugs available for treatment. Because of the range of symptoms of CFS/ME, treatment approaches vary widely. Studies undertaken have heterogeneous designs and are limited by sample size, length of follow‐up, applicability and methodological quality. The use of rintatolimod and rituximab as well as counselling, behavioural and rehabilitation therapy programs may be of benefit for CFS/ME, but the evidence of their effectiveness is still limited. Similarly, adaptive pacing appears to offer some benefits, but the results are debatable: so is the use of nutritional supplements, which may be of value to CFS/ME patients with biochemically proven deficiencies. To summarize, the recommended treatment strategies should include proper administration of nutritional supplements in CFS/ME patients with demonstrated deficiencies and personalized pacing programs to relieve symptoms and improve performance of daily activities, but a larger randomized controlled trial (RCT) evaluation is required to confirm these preliminary observations. At present, no firm conclusions can be drawn because the few RCTs undertaken to date have been small‐scale, with a high risk of bias, and have used different case definitions. Further, RCTs are now urgently needed with rigorous experimental designs and appropriate data analysis, focusing particularly on the comparison of outcomes measures according to clinical presentation, patient characteristics, case criteria and degree of disability (i.e. severely ill ME cases or bedridden).

Low-dose thalidomide is an effective treatment for refractory CLE, but its benefits need to be balanced against the potential adverse effects. Whereas DLE forms tended to relapse and required a long-term maintenance dose of thalidomide, SCLE forms showed a sustained remission after withdrawal.