Autoantibodies, polymorphisms in the serotonin pathway, and human leukocyte antigen class II alleles in chronic fatigue syndrome: are they associated with age at onset and specific symptoms?

Abstract:

This study aimed to determine the influence of autoantibodies, polymorphisms in the serotonin pathway, and human leukocyte antigen (HLA) class II genes on age at chronic fatigue syndrome (CFS) onset and symptoms.

Eighty-one CFS patients were enrolled, and clinical data were recorded. Autoantibodies to different components of the central nervous system were tested. Polymorphisms in the promoter of the serotonin transporter gene (l/s) and a single nucleotide polymorphism in the serotonin receptor-2A gene (A/G) as well as HLA class II alleles were determined. Multivariate logistic-regression analyses were carried out.

The mean age at CFS onset +/- SD was 33.5 +/- 12.5 years. An age at CFS onset (ACFSO) during the third decade of life was associated with the serotonin receptor AA genotype and the HLA-DRB1*03 allele. An ACFSO during the fourth decade of life was associated with the HLA-DRB1*07 allele, whereas an ACFSO > or = 43 years was associated with having at least one copy of the serotonin G allele.

Concerning CFS symptoms, the serotonin AG genotype was protective against depressive symptoms. Although having at least one copy of the serotonin A allele and being female were associated with risk for arthralgia, the presence of antineuronal cell antibodies was protective against this. Episodes of unexplained fever were associated with the HLA-DRB1*11 allele. None of the genetic or serological features was associated with myalgia. None of the antibodies determined correlated with any ACFSO or other symptoms.

Our results reveal that in CFS, like other autoimmune diseases, different genetic features are related to age at CFS onset and symptoms.

 

Source: Ortega-Hernandez OD, Cuccia M, Bozzini S, Bassi N, Moscavitch S, Diaz-Gallo LM, Blank M, Agmon-Levin N, Shoenfeld Y. Autoantibodies, polymorphisms in the serotonin pathway, and human leukocyte antigen class II alleles in chronic fatigue syndrome: are they associated with age at onset and specific symptoms? Ann N Y Acad Sci. 2009 Sep;1173:589-99. doi: 10.1111/j.1749-6632.2009.04802.x. https://www.ncbi.nlm.nih.gov/pubmed/19758204

 

When a parent is chronically ill: chronic fatigue syndrome

Abstract:

BACKGROUND: Chronic illness may reshape not only the life of the ill parent but also that of the entire family, but research in this area remains limited. More specifically, little is known about how an ill parent and the family respond to a particularly devastating and controversial chronic illness, chronic fatigue syndrome (CFS).

OBJECTIVES: The objective of this study was to describe the responses of the parent and the ensuing family system responses to the presence of chronic fatigue syndrome as a chronic parental illness.

METHODS: Parents were interviewed individually, and then the ill parent and as many immediate family members as possible were interviewed collectively. After consent or assent, interviews were audiotaped and transcribed. Thematic analyses at the individual, intrafamily, and across-family levels were used to explore these phenomena.

RESULTS: Eight ill parents first described the onset of illness, an ongoing struggle to receive diagnosis and care, and the significance of the illness in transforming present and future roles. Multiple members of the family together with the ill parent described how they struggled with the reality of the illness, the shifting roles and responsibilities, the reduced family income, and the frequent social isolation that could be exacerbated by the controversial nature of the illness. Families described and demonstrated their struggles to maintain normal family life and plans in the face of continuing uncertainty.

DISCUSSION: This study is situated within current scholarship on family responses to chronic parental illness. The value of the family research interview is affirmed. Recommendations are made for future directions in family nursing research exploring responses of families in which a parent is chronically ill.

 

Source: Donalek JG. When a parent is chronically ill: chronic fatigue syndrome. Nurs Res. 2009 Sep-Oct;58(5):332-9. doi: 10.1097/NNR.0b013e3181ac156f. https://www.ncbi.nlm.nih.gov/pubmed/19752673

 

Response to: exercise performance and chronic pain in chronic fatigue syndrome: the role of pain catastrophizing

Nijs and colleagues [1] have found various correlations; however, they have not proven the direction of causation or shown what can be done with the information. As is well known, pain can have a protective effect; conditions involving a lack of sensitivity to pain can cause all sorts of extra complications. Knowledge of why patients with chronic fatigue syndrome (CFS) experience pain following exercise is far from complete. However, studies in recent years such as by Jammes [2] and Sorensen [3] give possible clues that something abnormal biochemically occurs.

The authors found no association between either the current employment rate or the percentage difference between premorbid and current employment rate and either the Pain Catastrophizing Scale, the Beck Depression Inventory score or the SF-36 bodily pain score so none of these can explain the large drop in the employment rate found in the patients in this study and in other studies, suggesting the involvement of an independent variable. The single exercise test methodology used may not find the disease-specific factors associated with the exercise intolerance in CFS; repeat exercise testing such as 24 hours apart “may be necessary to document the atypical recovery response and protracted malaise unique to CFS”[4]. In the world of employment, most jobs do not involve just one intense burst of activity; continuous work, more comparable with repeat exercise testing, is generally required to hold on to a job.

The authors refer to CFS patients supposedly having “personality traits” “involving activity-avoidance.” However studies such as Harvey et al. [5] suggest CFS patients were more active than their contemporaries pre-illness suggesting that if patients avoid activity, it is unlikely to be due to “personality traits.”

You can read the rest of this comment here: http://painmedicine.oxfordjournals.org/content/10/6/1144.long

Comment on: Exercise performance and chronic pain in chronic fatigue syndrome: the role of pain catastrophizing. [Pain Med. 2008]

 

Source: Kindlon T. Response to: exercise performance and chronic pain in chronic fatigue syndrome: the role of pain catastrophizing. Pain Med. 2009 Sep;10(6):1144; author reply 1145-6. doi: 10.1111/j.1526-4637.2009.00690.x. Epub 2009 Sep 9. http://painmedicine.oxfordjournals.org/content/10/6/1144.long (Full article)

 

Effect of lixu jieyu recipe in treating 75 patients with chronic fatigue syndrome

Abstract:

OBJECTIVE: To investigate the effective Chinese medicine treatment of chronic fatigue syndrome (CFS).

METHODS: Seventy-five CFS patients meeting the inclusive criteria were enrolled from March 2007 to April 2008 and randomized into two groups. The 40 patients in the treated group were orally treated with Lixu Jieyu Recipe (LJR, consisted of milkvetch root 30 g, kudzuvine root 30 g, asiabell root 15 g, red sage root 10 g, aizoon stonecrop 15 g, epimeddium herb 10 g, curcuma root 10 g, and grassleaved sweetflag rhizome 10 g, made into 200 mL of decoction), for 100 mL twice a day. The 35 patients in the control group were treated with vitamin B tablets (10 mg twice a day), adenosine triphosphate (ATP, 20 mg, thrice a day) and Oryzanol tablets (20 mg thrice a day). The laboratory indicators including serum immunoglobulins (IgG, IgA, IgM, IgE), blood immune cells, as T-cells (Th and Ts), B-cells, natural killer cells, as well as CD4/CD8 ratio were measured before and after 3-month treatment.

RESULTS: After treatment the difference in scores of fatigue symptoms between the two groups was significant (P < 0.01), the scores of various SCL-90 factors and the total score significantly reduced in the treated group after treatment (P < 0.01). Levels of the immunoglobulins measured before treatment were in an equilibrium state, they all were unchanged after treatment in both groups (P > 0.05), and showed no significant difference between groups either before or after treatment. As for the immune cells, significant increase of the lowered Th, Ts cells, and decrease of CD4/CD8 ratio were found in both groups after treatment (P < 0.05), but the improvement was more significant in the treated group, so the difference between groups in these indices after treatment also showed statistical significance (P < 0.05).

CONCLUSION: LJR shows superiority in treating CFS.

 

Source: Zhang ZX, Wu LL, Chen M. Effect of lixu jieyu recipe in treating 75 patients with chronic fatigue syndrome. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2009 Jun;29(6):501-5. [Article in Chinese] https://www.ncbi.nlm.nih.gov/pubmed/19702080

 

The relationship of Fennell phases to symptoms among patients with chronic fatigue syndrome

Abstract:

The Fennell Phase Inventory (FPI) is an instrument designed to measure phases of the illnesses known as Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). The current study explored how the FPI was related to physical and psychological functioning as well as coping style. Based on FPI scores, 111 adults with ME/CFS were placed in one of three groups: crisis, stabilization, or resolution. Results showed that the crisis group demonstrated significantly worse functioning than at least one other group for depression, quality of life, mental functioning, anxiety, and self-efficacy; and utilized less adaptive coping styles. These results indicate that patients with ME/CFS who are in the crisis phase tend to experience more severe psychological and physical symptoms and utilize poorer coping strategies. Those in the resolution phase maintain the most adaptive coping strategies. Implications for these findings are discussed.

 

Source: Reynolds NL, Brown MM, Jason LA. The relationship of Fennell phases to symptoms among patients with chronic fatigue syndrome. Eval Health Prof. 2009 Sep;32(3):264-80. doi: 10.1177/0163278709338558. Epub 2009 Aug 20. https://www.ncbi.nlm.nih.gov/pubmed/19696083

 

Fatigue and chronic fatigue syndrome-like complaints in the general population

Abstract:

BACKGROUND: Most knowledge on chronic fatigue (CF) and chronic fatigue syndrome (CFS) is based on clinical studies, not representative of the general population. This study aimed to assess the prevalence of fatigue in an adult general population and to identify associations with lifestyle factors.

METHODS: Total 22,500 residents of Nijmegen were selected at random and interviewed by questionnaire. Data on 9062 respondents (43% response) were analysed, taken into account age, gender and concomitant disease. Subjects were classified into four groups: not fatigued (NF, reference group), short-term fatigue (SF, <6 months), chronic fatigue (CF, >or=6 months) and CFS-like fatigue (in accordance with the Center for Disease Control criteria for CFS, without clinical confirmation).

RESULTS: Our study population showed the following breakdown: NF 64.4% (95% CI 63.6-65.6%), SF 4.9% (95% CI 4.5-5.4%), CF 30.5% (95% CI 29.5-31.4%) and CFS-like fatigue 1.0% (95% CI 0.8-1.2%). Compared with the NF group, more of the CFS respondents were female [odds ratio (OR) = 1.9], obese (OR = 4.1), using analgesics (OR = 7.8), had a low alcohol intake (OR = 0.4), were eating less healthy food (OR = 0.5) and were physically less active (OR = 0.1). These associations largely applied to the SF and CF group. The fatigue could have been due to a concomitant disease in 34 and 55.5% of the SF and CF cases, respectively.

CONCLUSION: The prevalence of CF in the general population appears to be much higher than previously indicated. Even with strict criteria for CFS, it is estimated that approximately 1% of the adult population experiences this condition. Interestingly, a large part of this group remains unrecognized by the general practitioner. A striking similarity in lifestyle pattern between SF, CF and CFS calls for further research.

 

Source: van’t Leven M, Zielhuis GA, van der Meer JW, Verbeek AL, Bleijenberg G. Fatigue and chronic fatigue syndrome-like complaints in the general population. Eur J Public Health. 2010 Jun;20(3):251-7. doi: 10.1093/eurpub/ckp113. Epub 2009 Aug 18. http://eurpub.oxfordjournals.org/content/20/3/251.long (Full article)

 

Randomized controlled clinical trials of acupuncture treatment of chronic fatigue syndrome

Abstract:

OBJECTIVE: To observe the effect of acupuncture on the fatigue degree in patients with chronic fatigue syndrome (CFS).

METHODS: Seventy CFS patients were equally randomized into control and treatment groups according to randomized block design. Acupuncture was applied to Baihui (GV 20), Danzhong (CV 17), Zhongwan (CV 12), etc., for patients in treatment group, and to non-acupoints (2 cm respectively to the abovementioned acupoints) for those in control group. The treatment was given once every other day, 14 times altogether. The fatigue degree and the therapeutic effect were assessed by Chalder’s fatigue scale (FS).

RESULTS: A total of 64 cases (32/group) were finished in this study. After the treatment, the physical FS (5.0 +/- 2.4 vs 6.8 +/- 1.5), mental FS (1.8 +/-1.8 vs 3.1 +/- 1.5) and the total FS (6.8 +/- 3.8 vs 9.9 +/- 2.5) in treatment group, physical FS (5.0 +/- 2.5 vs 6.4 +/- 1.5) and the total FS (7.5 +/- 3.4 vs 9.6 +/- 2.8) in control group decreased significantly compared with pre-treatment (P < 0.01, P < 0.05). There was no marked change in mental FS (2.5 +/- 11.6 vs 3.2 +/- 11.6) in control group after the treatment (P > 0.05). Comparison between two groups showed no significant differences in the 3 indexes (P > 0.05).

CONCLUSION: Acupuncture can relieve CFS patients’ physical and mental fatigue and the therapeutic effect of acupuncture of acupoints is relatively better than that of non-acupoints in reducing mental fatigue.

 

Source: Wang JJ, Song YJ, Wu ZC, Chu XO, Wang QM, Wang XJ, Wei LN, Meng H, Wang XH. Randomized controlled clinical trials of acupuncture treatment of chronic fatigue syndrome. Zhen Ci Yan Jiu. 2009 Apr;34(2):120-4. [Article in Chinese] https://www.ncbi.nlm.nih.gov/pubmed/19685727

 

Chronic fatigue syndrome: a psychoneuroimmunological perspective

Abstract:

This article casts light on the contribution that psychoneuroimmunology can make in the search for the cause of chronic fatigue syndrome (cfs). Several studies suggest that psychosocial and physical stress may play an important predisposing, precipitating and perpetuating role in cfs. Moving on from these studies we now discuss recent research into the stress-related pathophysiological mechanisms of the illness. Although there is evidence for a hypofunctional stress response, a hyperactive immune response and disturbances in the interaction between both, the findings are not consistent. Longitudinal studies are needed to unravel the pathophysiology of cfs still further. In such studies the concept of ‘sickness response’ and ‘sickness behaviour’ may perform an important heuristic function.

 

Source: van Houdenhove B, Heijnen CJ. Chronic fatigue syndrome: a psychoneuroimmunological perspective. Tijdschr Psychiatr. 2009;51(8):603-10. [Article in Dutch] http://www.tijdschriftvoorpsychiatrie.nl/en/issues/413/articles/2821 (Full article)

 

Autoantibodies to lens epithelium-derived growth factor/transcription co-activator P75 (LEDGF/P75) in children with chronic nonspecific complaints and with positive antinuclear antibodies

Abstract:

Autoimmune fatigue syndrome (AIFS) is characterized by chronic nonspecific complaints, consistently positive antinuclear antibodies (ANA), and lack of alternate medical explanations. A newly recognized antibody, named anti-Sa, was detected in approximately 40% of the patients by Western blot (WB) using HeLa extract.

Some patients with AIFS later develop chronic fatigue syndrome (CFS), and most of them are positive for anti-Sa. On the other hand, Muro et al. reported anti-DFS70 in patients with CFS. Anti-Sa and anti-DFS70 were turned out to be same specificities by exchanging studies of blind sera. The target antigen of anti-DFS70 was identified as lens epithelium derived growth factor/transcription co-activator p75 (LEDGF/p75).

The objectives of this study are to confirm whether the target antigen of anti-Sa is also LEDGF/p75, and to develop ELISA system by using recombinant protein. Recombinant protein of LEDGF/p75 was purchased from Protein One (Bethesda, MD, USA). We developed an ELISA system to detect anti-LEDGF/p75 by coating this recombinant protein. 226 sera of AIFS patients (including 36 CFS patients) were applied to this ELISA assay and Western immunoblot, and it was revealed that anti-Sa-positive sera defined by WB and sera positive for anti-LEDGF/p75 on ELISA were identical.

Moreover, reactivities of anti-Sa on WB were inhibited by pre-incubating with recombinant LEDGF/p75, and eluted antibodies from the nitrocellulose membrane could react on the ELISA. These results confirm that the Sa antigen is LEDGF/p75. The ELISA assay using recombinant LEDGF/p75 could be a promising tool for measuring anti-Sa and consequently for diagnosing CFS.

 

Source: Kuwabara N, Itoh Y, Igarshi T, Fukunaga Y. Autoantibodies to lens epithelium-derived growth factor/transcription co-activator P75 (LEDGF/P75) in children with chronic nonspecific complaints and with positive antinuclear antibodies. Autoimmunity. 2009 Sep;42(6):492-6. Doi: 10.1080/08916930902736663. https://www.ncbi.nlm.nih.gov/pubmed/19657776

 

Moderate exercise increases expression for sensory, adrenergic, and immune genes in chronic fatigue syndrome patients but not in normal subjects

Abstract:

Chronic fatigue syndrome (CFS) is characterized by debilitating fatigue, often accompanied by widespread muscle pain that meets criteria for fibromyalgia syndrome (FMS). Symptoms become markedly worse after exercise. Previous studies implicated dysregulation of the sympathetic nervous system (SNS), and immune system (IS) in CFS and FMS.

We recently demonstrated that acid sensing ion channel (probably ASIC3), purinergic type 2X receptors (probably P2X4 and P2X5) and the transient receptor potential vanilloid type 1 (TRPV1) are molecular receptors in mouse sensory neurons detecting metabolites that cause acute muscle pain and possibly muscle fatigue. These molecular receptors are found on human leukocytes along with SNS and IS genes.

Real-time, quantitative PCR showed that 19 CFS patients had lower expression of beta-2 adrenergic receptors but otherwise did not differ from 16 control subjects before exercise. After a sustained moderate exercise test, CFS patients showed greater increases than control subjects in gene expression for metabolite detecting receptors ASIC3, P2X4, and P2X5, for SNS receptors alpha-2A, beta-1, beta-2, and COMT and IS genes for IL10 and TLR4 lasting from 0.5 to 48 hours (P < .05). These increases were also seen in the CFS subgroup with comorbid FMS and were highly correlated with symptoms of physical fatigue, mental fatigue, and pain.

These new findings suggest dysregulation of metabolite detecting receptors as well as SNS and IS in CFS and CFS-FMS.

PERSPECTIVE: Muscle fatigue and pain are major symptoms of CFS. After moderate exercise, CFS and CFS-FMS patients show enhanced gene expression for receptors detecting muscle metabolites and for SNS and IS, which correlate with these symptoms. These findings suggest possible new causes, points for intervention, and objective biomarkers for these disorders.

 

Source: Light AR, White AT, Hughen RW, Light KC. Moderate exercise increases expression for sensory, adrenergic, and immune genes in chronic fatigue syndrome patients but not in normal subjects. J Pain. 2009 Oct;10(10):1099-112. doi: 10.1016/j.jpain.2009.06.003. Epub 2009 Jul 31. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2757484/ (Full article)