Category: Immune System

Chronic fatigue syndrome is accompanied by an IgM-related immune response directed against neopitopes formed by oxidative or nitrosative damage to lipids and proteins

Abstract:

There is now some evidence that chronic fatigue syndrome (CFS) is accompanied by signs of oxidative stress and by a decreased antioxidant status. The aim of the present study was to examine whether CFS is accompanied by an immune response to neoepitopes of a variety of modified lipids and proteins indicating damage caused by oxidative and nitrosative stress. Toward this end we examined serum antibodies to fatty acids (oleic, palmitic and myristic acid), by-products of lipid peroxidation, i.e. azelaic acid and malondialdehyde (MDA), acetylcholine, S-farnesyl-L-cysteine, and N-oxide modified amino-acids in 14 patients with CFS, 14 subjects with partial CFS and 11 normal controls.

We found that the prevalences and mean values for the serum IgM levels directed against oleic, palmitic and myristic acid, MDA, azelaic acid, S-farnesyl-L-cysteine, and the N-oxide derivates, nitro-tyrosine, nitro-phenylalanine, nitro-arginine, nitro-tryptophan, and nitro-cysteinyl were significantly greater in CFS patients than in normal controls, whereas patients with partial CFS took up an intermediate position. There were significant and positive correlations between the serum IgM levels directed against fatty acids, MDA and azelaic acid and the above N-oxide-derivates and the severity of illness (as measured by the FibroFatigue scale) and symptoms, such as aches and pain, muscular tension and fatigue.

The results show that CFS is characterized by an IgM-related immune response directed against disrupted lipid membrane components, by-products of lipid peroxidation, S-farnesyl-L-cysteine, and NO-modified amino-acids, which are normally not detected by the immune system but due to oxidative and nitrosative damage have become immunogenic.

 

Source: Maes M, Mihaylova I, Leunis JC. Chronic fatigue syndrome is accompanied by an IgM-related immune response directed against neopitopes formed by oxidative or nitrosative damage to lipids and proteins. Neuro Endocrinol Lett. 2006 Oct;27(5):615-21. https://www.ncbi.nlm.nih.gov/pubmed/17159817

 

A case with chronic fatigue syndrome with positive antinuclear antibody followed by postpartum thyroiditis

Abstract:

Autoimmune fatigue syndrome (AIFS) is defined by chronic nonspecific complaints, a positive antinuclear antibody (ANA) assay, and the absence of another explanation for the complaints. Some severe cases fulfill the criteria for chronic fatigue syndrome (CFS). CFS is a syndrome characterized by disabling severe fatigue and defined by the criteria proposed by the U.S. Centers for Disease Control and Prevention. In this report, a patient with chronic fatigue syndrome and positive ANA assay was described as having developed postpartum thyroiditis 5 years after the onset. Sub-chemical hypothyroidism is characterized by clinical hypothyroidism not meeting biochemical criteria but showing evidence of thyroid autoimmunity. The relation between AIFS and sub-chemical hypothyroidism is discussed.

 

Source: Itoh Y, Hamada H, Igarashi T, Kuwabara N, Imai T, Fujino O, Fukunaga Y. A case with chronic fatigue syndrome with positive antinuclear antibody followed by postpartum thyroiditis. Mod Rheumatol. 2004;14(5):406-9. https://www.ncbi.nlm.nih.gov/pubmed/17143702

 

Increased serum IgA and IgM against LPS of enterobacteria in chronic fatigue syndrome (CFS): indication for the involvement of gram-negative enterobacteria in the etiology of CFS and for the presence of an increased gut-intestinal permeability

Abstract:

There is now evidence that chronic fatigue syndrome (CFS) is accompanied by immune disorders and by increased oxidative stress. The present study has been designed in order to examine the serum concentrations of IgA and IgM to LPS of gram-negative enterobacteria, i.e. Hafnia alvei; Pseudomonas aeruginosa, Morganella morganii, Proteus mirabilis, Pseudomonas putida, Citrobacter koseri, and Klebsiella pneumoniae in CFS patients, patients with partial CFS and normal controls.

We found that the prevalences and median values for serum IgA against the LPS of enterobacteria are significantly greater in patients with CFS than in normal volunteers and patients with partial CFS. Serum IgA levels were significantly correlated to the severity of illness, as measured by the FibroFatigue scale and to symptoms, such as irritable bowel, muscular tension, fatigue, concentration difficulties, and failing memory.

The results show that enterobacteria are involved in the etiology of CFS and that an increased gut-intestinal permeability has caused an immune response to the LPS of gram-negative enterobacteria. It is suggested that all patients with CFS should be checked by means of the IgA panel used in the present study and accordingly should be treated for increased gut permeability.

 

Source: Maes M, Mihaylova I, Leunis JC. Increased serum IgA and IgM against LPS of enterobacteria in chronic fatigue syndrome (CFS): indication for the involvement of gram-negative enterobacteria in the etiology of CFS and for the presence of an increased gut-intestinal permeability. J Affect Disord. 2007 Apr;99(1-3):237-40. Epub 2006 Sep 27. https://www.ncbi.nlm.nih.gov/pubmed/17007934

 

Impaired natural immunity, cognitive dysfunction, and physical symptoms in patients with chronic fatigue syndrome: preliminary evidence for a subgroup?

Abstract:

OBJECTIVE: The diagnostic criteria of chronic fatigue syndrome (CFS) define a heterogeneous population composed of several subgroups. Past efforts to identify subgroup markers have met with mixed success. This study was designed to examine natural killer cell activity (NKCA) as a potential subgroup marker by comparing the clinical presentations of CFS patients with and without clinically reduced NKCA.

METHODS: Forty-one female CFS patients were classified into having either low or normal NKCA levels. These subgroups were then compared on objective measures of cognitive functioning and subjective assessments of fatigue, vigor, cognitive impairment, and daytime dysfunction.

RESULTS: Relative to CFS patients in the normal-NKCA subgroup, low-NKCA patients reported less vigor, more daytime dysfunction, and more cognitive impairment. In addition, low-NKCA patients performed less on objective measures of cognitive functioning relative to normal-NKCA patients.

CONCLUSIONS: The results are offered as preliminary evidence in support of using NKCA as an immunological subgroup marker in CFS. Findings are also discussed in terms of known associations between dysregulated immune functions, somatic symptoms, and psychological stress.

 

Source: Siegel SD, Antoni MH, Fletcher MA, Maher K, Segota MC, Klimas N. Impaired natural immunity, cognitive dysfunction, and physical symptoms in patients with chronic fatigue syndrome: preliminary evidence for a subgroup? J Psychosom Res. 2006 Jun;60(6):559-66. https://www.ncbi.nlm.nih.gov/pubmed/16731230

 

Lower serum zinc in Chronic Fatigue Syndrome (CFS): relationships to immune dysfunctions and relevance for the oxidative stress status in CFS

Abstract:

The present study examines serum zinc concentrations in patients with chronic fatigue syndrome (CFS) versus normal volunteers. Serum zinc levels were determined by means of an atomic absorption method.

We found that serum zinc was significantly lower in the CFS patients than in the normal controls. There was a trend toward a significant negative correlation between serum zinc and the severity of CFS and there was a significant and negative correlation between serum zinc and the subjective experience of infection. We found that serum zinc was significantly and negatively correlated to the increase in the alpha2 protein fraction and positively correlated to decreases in the expression of mitogen-induced CD69+ (a T cell activation marker) on CD3+ as well as CD3+CD8+ T cells.

These results show that CFS is accompanied by a low serum zinc status and that the latter is related to signs of inflammation and defects in early T cell activation pathways. Since zinc is a strong anti-oxidant, the present results further support the findings that CFS is accompanied by increased oxidative stress. The results of these reports suggest that some patients with CFS should be treated with specific antioxidants, including zinc supplements.

 

Source: Maes M, Mihaylova I, De Ruyter M. Lower serum zinc in Chronic Fatigue Syndrome (CFS): relationships to immune dysfunctions and relevance for the oxidative stress status in CFS. J Affect Disord. 2006 Feb;90(2-3):141-7. Epub 2005 Dec 9. http://www.ncbi.nlm.nih.gov/pubmed/16338007

 

Chronic fatigue syndrome is associated with diminished intracellular perforin

Abstract:

Chronic fatigue syndrome (CFS) is an illness characterized by unexplained and prolonged fatigue that is often accompanied by abnormalities of immune, endocrine and cognitive functions. Diminished natural killer cell cytotoxicity (NKCC) is a frequently reported finding. However, the molecular basis of this defect of in vitro cytotoxicy has not been described.

Perforin is a protein found within intracellular granules of NK and cytotoxic T cells and is a key factor in the lytic processes mediated by these cells. Quantitative fluorescence flow cytometry was used to the intracellular perforin content in CFS subjects and healthy controls.

A significant reduction in the NK cell associated perforin levels in samples from CFS patients, compared to healthy controls, was observed. There was also an indication of a reduced perforin level within the cytotoxic T cells of CFS subjects, providing the first evidence, to our knowledge, to suggest a T cell associated cytotoxic deficit in CFS. Because perforin is important in immune surveillance and homeostasis of the immune system, its deficiency may prove to be an important factor in the pathogenesis of CFS and its analysis may prove useful as a biomarker in the study of CFS.

 

Source: Maher KJ, Klimas NG, Fletcher MA. Chronic fatigue syndrome is associated with diminished intracellular perforin. Clin Exp Immunol. 2005 Dec;142(3):505-11. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1440524/ (Full article)

 

Decreased dehydroepiandrosterone sulfate but normal insulin-like growth factor in chronic fatigue syndrome (CFS): relevance for the inflammatory response in CFS

Abstract:

There are a few reports that chronic fatigue syndrome (CFS) may be accompanied by changes in hormones, such as dehydroepiandrosterone (DHEA) and insulin-like growth factor (IGF1). This study examines the serum concentrations of DHEA-sulfate (DHEAS), IGF1 and IGF1 binding protein-3 (IGFBP3) in 20 patients with CFS and in 12 normal controls.

The IGFBP3/IGF1 ratio was computed as an index for IGF1 availability. We found significantly lower serum DHEAS concentrations in CFS, but no significant differences either in IGF1 or the IGFBP3/IGF1 ratio between CFS patients and normal controls. The decrease in serum DHEAS was highly sensitive and specific for CFS.

There were significant and positive correlations between serum DHEAS and serum zinc and the mitogen-induced expression of the CD69 molecule on CD3+CD8+ T cells (an indicator of early T cell activation). There was a significant and negative correlation between serum DHEAS and the increase in the serum alpha-2 protein fraction (an inflammatory marker). Serum IGF1, but not DHEAS, was significantly and inversely correlated to age.

The results show that CFS is accompanied by lowered levels of DHEAS and that the latter may play a role in the immune (defect in the early activation of T cells) and the inflammatory pathophysiology of CFS.

 

Source: Maes M, Mihaylova I, De Ruyter M. Decreased dehydroepiandrosterone sulfate but normal insulin-like growth factor in chronic fatigue syndrome (CFS): relevance for the inflammatory response in CFS. Decreased dehydroepiandrosterone sulfate but normal insulin-like growth factor in chronic fatigue syndrome (CFS): relevance for the inflammatory response in CFS. Neuro Endocrinol Lett. 2005 Oct;26(5):487-92. http://www.ncbi.nlm.nih.gov/pubmed/16264414

 

Chronic fatigue syndrome: exercise performance related to immune dysfunction

Abstract:

PURPOSE: To date, the exact cause of abnormal exercise response in chronic fatigue syndrome (CFS) remains to be revealed, but evidence addressing intracellular immune deregulation in CFS is growing. Therefore, the aim of this cross-sectional study was to examine the interactions between several intracellular immune variables and exercise performance in CFS patients.

METHODS: After venous blood sampling, subjects (16 CFS patients) performed a maximal exercise stress test on a bicycle ergometer with continuous monitoring of cardiorespiratory variables. The following immune variables were assessed: the ratio of 37 kDa Ribonuclease (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 (enzymatic-colorimetric assay), the percent of monocytes, and nitric oxide determination (for monocytes and lymphocytes; flow cytometry, live cell assay).

RESULTS: Forward stepwise multiple regression analysis revealed 1) that elastase activity was the only factor related to the reduction in oxygen uptake at a respiratory exchange ratio (RER) of 1.0 (regression model: R = 0.53, F (1,14) = 15.5, P < 0.002; elastase activity P < 0.002); 2) that the protein kinase R activity was the principle factor related to the reduction in workload at RER = 1.0; and 3) that elastase activity was the principle factor related to the reduction in percent of target heart rate achieved.

CONCLUSION: These data provide evidence for an association between intracellular immune deregulation and exercise performance in patients with CFS. To establish a causal relationship, further study of these interactions using a prospective longitudinal design is required.

 

Source: Nijs J, Meeus M, McGregor NR, Meeusen R, de Schutter G, van Hoof E, de Meirleir K. Chronic fatigue syndrome: exercise performance related to immune dysfunction. Med Sci Sports Exerc. 2005 Oct;37(10):1647-54. http://www.ncbi.nlm.nih.gov/pubmed/16260962

 

Association of chronic fatigue syndrome with human leucocyte antigen class II alleles

Abstract:

BACKGROUND: A genetic component to the development of chronic fatigue syndrome (CFS) has been proposed, and a possible association between human leucocyte antigen (HLA) class II antigens and chronic fatigue immune dysfunction has been shown in some, but not all, studies.

AIMS: To investigate the role of HLA class II antigens in CFS.

METHODS: Forty nine patients with CFS were genotyped for the HLA-DRB1, HLA-DQA1, and HLA-DQB1 alleles and the frequency of these alleles was compared with a control group comprising 102 normal individuals from the UK. All patients and controls were from the same region of England and, apart from two patients, were white.

RESULTS: Analysis by 2 x 2 contingency tables revealed an increased frequency of HLA-DQA1*01 alleles in patients with CFS (51.0% v 35%; odds ratio (OR), 1.93; p = 0.008). HLA-DQB1*06 was also increased in the patients with CFS (30.2% v 20.0%; OR, 1.73, p = 0.052). Only the association between HLA-DQA1*01 and CFS was significant in logistic regression models containing HLA-DQA1*01 and HLA-DRQB1*06, and this was independent of HLA-DRB1 alleles. There was a decreased expression of HLA-DRB1*11 in CFS, although this association disappeared after correction for multiple comparisons.

CONCLUSIONS: CFS may be associated with HLA-DQA1*01, although a role for other genes in linkage disequilibrium cannot be ruled out.

 

Source: Smith J, Fritz EL, Kerr JR, Cleare AJ, Wessely S, Mattey DL. Association of chronic fatigue syndrome with human leucocyte antigen class II alleles. J Clin Pathol. 2005 Aug;58(8):860-3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1770867/ (Full article)

 

 

Lymphocyte subset differences in patients with chronic fatigue syndrome, multiple sclerosis and major depression

Abstract:

Chronic fatigue syndrome (CFS) is a heterogeneous disorder of unknown aetiology characterized by debilitating fatigue, along with other symptoms, for at least 6 months. Many studies demonstrate probable involvement of the central and autonomic nervous system, as well as a state of generalized immune activation and selective immune dysfunction in patients with CFS. The aim of this study was to compare the lymphocyte subsets of patients with chronic fatigue syndrome to those of patients with major depression and multiple sclerosis as well as those of healthy control subjects.

No differences were found in total numbers of T cells, B cells or natural killer (NK) cells. However, differences were found in T, B and NK cell subsets. Patients with major depression had significantly fewer resting T (CD3(+)/CD25(-)) cells than the other groups. Patients with major depression also had significantly more CD20(+)/CD5(+) B cells, a subset associated with the production of autoantibodies.

Compared to patients with multiple sclerosis, patients with CFS had greater numbers of CD16(+)/CD3(-) NK cells. Further study will be required to determine whether these alterations in lymphocyte subsets are directly involved in the pathophysiology of these disorders, or are secondary effects of the causal agent(s).

 

Source: Robertson MJ, Schacterle RS, Mackin GA, Wilson SN, Bloomingdale KL, Ritz J, Komaroff AL. Lymphocyte subset differences in patients with chronic fatigue syndrome, multiple sclerosis and major depression. Clin Exp Immunol. 2005 Aug;141(2):326-32. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1809442/ (Full article)