Article

Identification of marker genes for differential diagnosis of chronic fatigue syndrome

Department of General Medicine, Nagoya University Hospital, Nagoya, Japan.
Molecular Medicine (Impact Factor: 4.82). 08/2008; 14(9-10):599-607. DOI: 10.2119/2007-00059.Saiki
Source: PubMed

ABSTRACT Chronic fatigue syndrome (CFS) is a clinically defined condition characterized by long-lasting disabling fatigue. Because of the unknown mechanism underlying this syndrome, there still is no specific biomarker for objective assessment of the pathological fatigue. We have compared gene expression profiles in peripheral blood between 11 drug-free patients with CFS and age- and sex-matched healthy subjects using a custom microarray carrying complementary DNA probes for 1,467 stress-responsive genes. We identified 12 genes whose mRNA levels were changed significantly in CFS patients. Of these 12 genes, quantitative real-time PCR validated the changes in 9 genes encoding granzyme in activated T or natural killer cells (GZMA), energy regulators (ATP5J2, COX5B, and DBI), proteasome subunits (PSMA3 and PSMA4), putative protein kinase c inhibitor (HINT ), GTPase (ARHC), and signal transducers and activators of transcription 5A (STAT5A). Next, we performed the same microarray analysis on 3 additional CFS patients and 20 other patients with the chief complaint of long-lasting fatigue related to other disorders (non-CFS patients) and found that the relative mRNA expression of 9 genes classified 79% (11/14) of CFS and 85% (17/20) of the non-CFS patients. Finally, real-time PCR measurements of the levels of the 9 involved mRNAs were done in another group of 18 CFS and 12 non-CFS patients. The expression pattern correctly classified 94% (17/18) of CFS and 92% (11/12) of non-CFS patients. Our results suggest that the defined gene cluster (9 genes) may be useful for detecting pathological responses in CFS patients and for differential diagnosis of this syndrome.

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    • "However, until now the role of viral infections as etiological agents for ME/CFS has been evaluated inconsistently [12] [13] [14] [15]. Identification of specific biomarkers for differential diagnosis of ME/CFS has intensively been studied [16] [17] [18] [19]. HHV-6 and HHV-7 are lymphotropic, neurotropic, and immunomodulating viruses which primary infection is followed by lifelong persistency. "
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    ABSTRACT: Frequency of active human herpesvirus-6, -7 (HHV-6, HHV-7) and parvovirus B19 (B19) infection/coinfection and its association with clinical course of ME/CFS was evaluated. 108 ME/CFS patients and 90 practically healthy persons were enrolled in the study. Viral genomic sequences were detected by PCR, virus-specific antibodies and cytokine levels-by ELISA, HHV-6 variants-by restriction analysis. Active viral infection including concurrent infection was found in 64.8% (70/108) of patients and in 13.3% (12/90) of practically healthy persons. Increase in peripheral blood leukocyte DNA HHV-6 load as well as in proinflammatory cytokines' levels was detected in patients during active viral infection. Definite relationship was observed between active betaherpesvirus infection and subfebrility, lymphadenopathy and malaise after exertion, and between active B19 infection and multijoint pain. Neuropsychological disturbances were detected in all patients. The manifestation of symptoms was of more frequent occurrence in patients with concurrent infection. The high rate of active HHV-6, HHV-7 and B19 infection/coinfection with the simultaneous increase in plasma proinflammatory cytokines' level as well as the association between active viral infection and distinctive types of clinical symptoms shows necessity of simultaneous study of these viral infections for identification of possible subsets of ME/CFS.
    Advances in Virology 08/2012; 2012:205085. DOI:10.1155/2012/205085
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    • "Consistent data worldwide suggest that a decrease in cytotoxic activity is a hallmark of CFS. In most cases this decrease has been associated with differential expression in cytotoxic molecules including GZMA, GZMK, GZMB and PRF1 (Brenu et al., 2011b; Saiki et al., 2008). "
    An International Perspective on the Future of Research in Chronic Fatigue Syndrome, 02/2012; , ISBN: 978-953-51-0072-0
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    • "An inflamma tory response has been established in many ME/CFS patients (Maes, 2009), while the immune system also seems to be dysfunctional and depressed (Lorusso et al. 2009). Over time researchers have shown various immune system abnormalities, like decrea sed natural killer cell activity (Saiki et al. 2008; Nijs & de Meirleir, 2005; Klimas et al. 1990), reduced perforin levels in cytotoxic T and NK cells (Maher et al. 2005), defects in T-and NK cell activation (Mihaylova et al. 2007; Maes et al. 2006), a significant decrease in the suppressor inducer subset of CD4+CD45RA+ cells (Klimas et al. 1990), a significant bias towards Th2-and Tc2-type immune responses (Skowera et al. 2004), and dysregula tion of the RNAse L pathway (Suhadolnik et al. 1997; Englebienne & de Meirleir, 2002; Tiev et al. 2003). A central role for immune system abnormalities , inflammation and immune dysfunction, in the pathophysiology of ME/CFS have also been implicated by several gene expression studies (Kaushik et al. 2005; Kerr et al. 2008; Broderick et al. 2006; Aspler et al. 2008, Gow et al. 2009). "
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    ABSTRACT: Benign Myalgic Encephalomyelitis (ME) / Chronic Fatigue Syndrome (CFS) is a debilitating disease which, despite numerous biological abnormalities has remained highly controversial. Notwithstanding the medical pathogenesis of ME/CFS, the (bio)psychosocial model is adopted by many governmental organizations and medical profes-sio-nals to legitimize the combination of Cognitive Behavioral Therapy (CBT) and Graded Exercise Therapy (GET) for ME/CFS. Justified by this model CBT and GET aim at eliminating presumed psychogenic and socially induced maintaining factors and reversing deconditioning, respectively. In this review we invalidate the (bio)psychosocial model for ME/CFS and demonstrate that the success claim for CBT/GET to treat ME/CFS is unjust. CBT/GET is not only hardly more effective than non-interventions or standard medical care, but many patients report that the therapy had affected them adversely, the majority of them even reporting substantial deterioration. Moreover, this review shows that exertion and thus GET most likely have a negative impact on many ME/CFS patients. Exertion induces post-exertional malaise with a decreased physical performan-ce/aerobic capacity, increased muscoskeletal pain, neurocognitive impairment, "fatigue", and weakness, and a long lasting "recovery" time. This can be explained by findings that exertion may amplify pre-existing pa-thophysiological abnormalities underpinning ME/CFS, such as inflammation, immune dysfunction, oxidative and nitrosative stress, channelopathy, defec-tive stress response mechanisms and a hypoactive hypothalamic-pituitary-adrenal axis. We conclude that it is unethical to treat patients with ME/CFS with ineffective, non-evidence-based and potentially harmful "rehabilitation therapies", such as CBT/GET.
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