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© 2016 The Author(s)Myalgic encephalomyelitis (ME) is a complex, heterogeneous illness of unknown etiology. The search for biomarkers that can delineate cases from controls is one of the most active areas of ME research; however, little progress has been made in achieving this goal. In contrast to identifying biomarkers that are directly involved in the pathological process, an immunosignature identifies antibodies raised to proteins expressed during, and potentially involved in, the pathological process. Although these proteins might be unknown, it is possible to detect antibodies that react to these proteins using random peptide arrays. In the present study, we probe a custom 125,000 random 12-mer peptide microarray with sera from 21 ME cases and 21 controls from the USA and Europe and used these data to develop a diagnostic signature. We further used these peptide sequences to potentially uncover the naturally occurring candidate antigens to which these antibodies may specifically react with in vivo. Our analysis revealed a subset of 25 peptides that distinguished cases and controls with high specificity and sensitivity. Additionally, Basic Local Alignment Search Tool (BLAST) searches suggest that these peptides primarily represent human self-antigens and endogenous retroviral sequences and, to a minor extent, viral and bacterial pathogens.

OBJECTIVE To investigate the effects of cold application with different temperatures on lymph flow in healthy persons and to examine the effects of the combination of cold and compression on lymph vessels. PARTICIPANTS Thirty-nine healthy persons were included in the study, and each served as his or her own control. INTERVENTION Water bags (1 degree, 15 degrees, and 32 degrees) with or without 25 mm Hg pressure were applied to the experimental legs for 30 minutes. Cold, pressure, or both were administered by an Aircast-Cryo-cuff (Aircast Europe GMBH, Rosenheim, Germany). MAIN OUTCOME MEASURES Skin temperature was measured with a TESTO 901 (Testoterm GMBH, Leuven, Belgium) precision thermometer. Lymph flow was recorded continuously using lymphoscintigraphy. MANOVA with repeated measures was used for data analysis. RESULTS As expected, skin temperature dropped relative to the temperature of the water. The migration of the tracer was comparable in both ankles during the first 30 minutes of the experiment (rest). When the water bag was applied, lymph flow increased significantly (p < 0.01). The application of water of 1 degree C without pressure influenced lymph evacuation significantly differently from the other temperatures. The application of pressure of 25 mm Hg influenced lymph evacuation significantly at 1 degree C and 32 degrees C. CONCLUSION These results indicate that lymph evacuation at the ankle is influenced significantly when cold water is applied with or without pressure. When pressure is added to the application of water of 32 degrees C, lymph flow will also increase significantly, indicating the importance of pressure in lymph evacuation.

The marked depletion of dendritic cells (DCs) in skin cancers, as well as preneoplastic and neoplastic cervical epithelium, suggests a central role for DCs in productive human papillomavirus (HPV) infection and cancer promotion. It has been suggested that HPV may facilitate tumor development by reducing DC density, contributing to a decrease in local immune surveillance. In this study, we have examined the response of human DCs transfected with a construct containing the HPV18 genome and their subsequent expression of papilloma virus proteins. Transfected cells expressed the L1 major capsid protein and upregulated E6 and E7 oncoprotein transcripts as detected by RT-PCR. Transfection of DCs also resulted in a significant increase in cytokine production. Finally, we observed that HPV18 transfection decreased the migratory activity of DCs. Our data indicate that HPV transfection of DCs leads to changes in migratory activity and cytokine production, which potentially can suppress or delay immune responses to viral antigens. Additionally, changes in cytokine production by HPV-transformed human fibroblasts and human cervical epithelial cells revealed that the migratory and antigen-presenting functions of DCs may be impaired by the suppressive effects of cytokines produced by HPV-infected epithelial and stromal cells.

Myalgic encephalomyelitis (ME) is a debilitating illness of unknown etiology characterized by neurocognitive dysfunction, inflammation, immune abnormalities and gastrointestinal distress. An increasing body of evidence suggests that disruptions in the gut may contribute to the induction of neuroinflammation. Therefore, reports of human endogenous retroviral (HERV) expression in association with neuroinflammatory diseases prompted us to investigate the gut of individuals with ME for the presence of HERV proteins. In eight out of 12 individuals with ME, immunoreactivity to HERV proteins was observed in duodenal biopsies. In contrast, no immunoreactivity was detected in any of the eight controls. Immunoreactivity to HERV Gag and Env proteins was uniquely co-localized in hematopoietic cells expressing the C-type lectin receptor CLEC4C (CD303/BDCA2), the costimulatory marker CD86 and the class II major histocompatibility complex HLA-DR, consistent with plasmacytoid dendritic cells (pDCs). Although the significance of HERVs present in the pDCs of individuals with ME has yet to be determined, these data raise the possibility of an involvment of pDCs and HERVs in ME pathology. To our knowledge, this report describes the first direct association between pDCs and HERVs in human disease.

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Patiënten met het chronische–vermoeidheidsyndroom (CVS) rapporteren een verminderde levenskwaliteit door onder andere beperkte cognitieve functies, zoals aandacht en geheugen. Deze subjectief gemelde beperkingen kunnen echter niet altijd geobjectiveerd worden. In onderzoek waarover in deze bijdrage wordt gerapporteerd, wordt een minimale neurocognitieve testbatterij gebruikt die eveneens aansluit bij de wetenschappelijke literatuur. 71 patiënten met CVS en 28 sedentaire gezonde controlepersonen worden onderworpen aan een neurocognitieve screening. Een gezonde controlegroep wordt verkozen boven personen met een andere vermoeidheidsgerelateerde aandoening daar patiënten met CVS in de praktijk eveneens vergeleken worden met gezonde, werkende mensen. Aandachts- en geheugenbeperkingen, alsook een verminderde reactiesnelheid lijken aanwezig in de CVS-populatie. Bovendien beïnvloeden deze klachten significant hun dagelijks leven. Uit dit cross-sectioneel onderzoek blijkt het nut van een reactietijdtest, onderzoek naar motorische snelheid, een aandachtstest en een woordvloeiendheidstest als een minimale testbatterij.

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Introduction: Previous research has shown that patients with Chronic Fatigue Syndrome (CFS) present with an abnormal exercise response and exacerbation of symptoms after physical activity. Preliminary evidence for an association between the deregulation of the 2 ,5 -oligoadenylate (2-5A) synthetase/RNase (ribonuclease) L pathway and impairments of exercise capacity has been provided. This cross-sectional study aimed at examining the associations between the various components of the 2-5A synthetase/RNase L pathway and impairments of cardiorespiratory fi tness in CFS patients. Methods: Sixteen randomly allocated CFS underwent venous blood sampling and performed a maximally exercise stress test on a bicycle ergometer with continuous monitoring of cardiorespiratory parameters. The following blood parameters were assessed: the ratio of 37 kDa RNase L to the 83 kDa native RNase L (using a radiolabeled ligand/receptor assay), RNase L enzymatic activity (enzymatic assay), protein kinase R activity assay (comparison Western blot), elastase activity in monocytes and lymphocytes (enzymatic colorimetric assay), the number and % of monocytes and lymphocytes; and nitric oxide determination (for monocytes and lymphocytes; fl ow cytometry, live cell assay). Results: Forward stepwise multiple regression analysis revealed 1/ that the level of elastase was the only factor related to the reduction in oxygen uptake at a respiratory quotient (RQ) of 1.0 (regression model: R2=.53,F(1,14)=15.5,pactivity was the principle factor related to the reduction in workload at RQ=1.0 (R2=.77,F(6,9) =5.2,pL ratio pprinciple factor related to the reduction in % of target heart rate achieved (R2=.89,F(7,8)=9.5,p< .002; elastase pConclusion: These data provide evidence for an association between intracellular immune deregulation and impairments in cardiorespiratory fi tness in CFS. To establish a causal relationship, however, further studying of these interactions in a larger study sample and using a prospective longitudinal design is required.

Objective: The aim of this study was to determine if hyperbaric oxygen treatment (HBOT) could be used as adjunctive therapy and if HBOT could increase the quality of life in such a way that the functional status would improve in patients with an infection. Methods: Randomized, controlled trial: Fifteen infected CFS (CDC 1994) patients and 14 CFS (CDC 1994) patients with no evidence of a mycoplasma infection were enrolled in a convenience randomisation sample from our referral clinic. Results: No Statistical differences were found by use of univariate repeated measures although Bodily Pain as measured by the SF-36 seems to decrease after hyperbaric therapy (Greenhouse-Geisser: p = .010). Trends were found using paired t-testing for mycoplasma infected CFS patients. The general perceived fatigue seemed to decrease after hyperbaric therapy (General Fatigue: p = .06). Directly after one week of hyperbaric therapy general fatigue improved (p = .03) but there was a reduction of activity (reduced activity: p= .05) and general perceived health (general health: p = .04). One month later the physical role increased (Role-Physical: p = .07). Conclusions: Although more data is required to make firm conclusions, trends were found. Reduced fatigue, increased levels of activity and an improved reaction time improved significantly their quality of life and therfore, enhanced also their functional status and thus could be used as an adjunctive therapy.