Category: Immune System

Clinical laboratory test findings in patients with chronic fatigue syndrome

Abstract:

BACKGROUND: Results of readily available clinical laboratory tests in patients with chronic fatigue syndrome were compared with results in healthy control subjects.

METHODS: Cases consisted of all 579 patients who met either the Centers for Disease Control and Prevention, Atlanta, Ga, British, or Australian case definition for chronic fatigue syndrome. They were from chronic fatigue clinics in Boston, Mass, and Seattle, Wash. Control subjects consisted of 147 blood donors who denied chronic fatigue. Outcome measures were the results of 18 clinical laboratory tests.

RESULTS:Age- and sex-adjusted odds ratios of abnormal results, comparing cases with control subjects, were as follows: circulating immune complexes, 26.5 (95% confidence interval [CI] 3.4-206), atypical lymphocytosis, 11.4 (95% CI, 1.4-94); elevated immunoglobulin G, 8.5 (95% CI, 2.0-37); elevated alkaline phosphatase, 4.2 (95% CI, 1.6-11); elevated total cholesterol, 2.1 (95% CI, 1.2-3.4); and elevated lactic dehydrogenase, 0.30 (95% CI, 0.16-0.56). Also, antinuclear antibodies were detected in 15% of cases vs 0% in the control subjects. The results of these tests were generally comparable for the cases from Seattle and Boston. Although these tests served to discriminate the population of patients from healthy control subjects, at the individual level they were not as useful.

CONCLUSIONS: Patients with chronic fatigue syndrome who were located in two geographically distant areas had abnormalities in the results of several readily available clinical laboratory tests compared with healthy control subjects. The immunologic abnormalities are in accord with a growing body of evidence suggesting chronic, low-level activation of the immune system in chronic fatigue syndrome. While each of these laboratory findings supports the diagnosis of chronic fatigue syndrome, each lacks sufficient sensitivity to be a diagnostic test. Furthermore, the specificity of these findings relative to other organic and psychiatric conditions that can produce fatigue remains to be established.

Comment in: Clinical laboratory test findings in patients with chronic fatigue syndrome. [Arch Intern Med. 1995]

 

Source: Bates DW, Buchwald D, Lee J, Kith P, Doolittle T, Rutherford C, Churchill WH, Schur PH, Wener M, Wybenga D, et al. Clinical laboratory test findings in patients with chronic fatigue syndrome. Arch Intern Med. 1995 Jan 9;155(1):97-103. http://www.ncbi.nlm.nih.gov/pubmed/7632202

 

Immunological abnormalities in patients with chronic fatigue syndrome

Abstract:

Between January 1991 and January 1993, 265 patients who fulfilled the CDC criteria of the working case definition of Chronic Fatigue Syndrome (CFS) have been observed at our Institution and submitted for clinical and laboratory evaluation.

One hundred and sixty-three patients were females and 102 males, the median age was 35 years (range 4-55 years); all patients reported profound and prolonged fatigue, lasting for a median of 3 years (range 6 months-10 years), preceded or accompanied at appearance by fever in 185 cases, and neuropsychologic problems including inability to concentrate, difficulty in thinking, confusion, irritability, forgetfulness, and depression. The fatigue was so severe that it required 102 patients to stop their working activities for a period of time ranging from 3 months to 2 years (range 7 months).

In 40 consecutive patients a comprehensive immunologic testing by single and two-colour flow cytometry was performed and results compared with a group of 35 healthy, age- and sex-matched controls. Whilst no significant differences were found in the absolute numbers of circulating total T cells (CD3+) and of total helper/inducer (CD4+) or suppressor/cytotoxic (CD8+) T cells, an evident reduction in CD3-/CD16+ and CD57+/CD56+ NK lymphocytes along with an expansion of the CD8+/CD56+ and CD16-/CD56+ NK subsets, were found in the CFS group.

In addition, CD56+ NK cells from CFS subjects were found to express an increased amount of cell adhesion molecules (CD11b, CD11c, CD54) and activation antigens (CD38). Both the percentage and absolute numbers of CD4+ T cells bearing the CD45RA antigen appeared significantly reduced in CFS patients, and CD4+ T lymphocytes from CFS subjects displayed an increased expression of the intercellular adhesion molecule-1 (ICAM-1/CD54).

Finally, the total numbers of circulating (CD19+) B lymphocytes, were significantly higher in CFS cases than in controls, and in 11 out of 30 CFS patients the increase in circulating B cells was sustained by the expansion of the CD5+/CD19+ subset of B lymphocytes.

We conclude that CFS is a syndrome not previously described in Italy, with already known clinical characteristics and appears to be associated with several immunologic abnormalities, including those reported previously in cohort of patients from different countries. We also show for the first time that CD56- NK cell subsets from CFS patients display an abnormally increased expression of cell adhesion molecules and activation markers.

 

Source: Tirelli U, Marotta G, Improta S, Pinto A. Immunological abnormalities in patients with chronic fatigue syndrome. Scand J Immunol. 1994 Dec;40(6):601-8. http://www.ncbi.nlm.nih.gov/pubmed/7997849

 

Chronic fatigue syndrome–a controlled cross-sectional study

Abstract:

Twenty-one patients fulfilling the Center for Disease Control criteria for chronic fatigue syndrome (CFS) were examined in a controlled study. Viral antibodies and tests evaluating the immune system were investigated in the patients and in a control group of 21 sex- and age-matched individuals.

Production in vitro of the predominantly T-cell-derived cytokines interleukin-2 and interferon-gamma was significantly higher in patients with CFS compared the control group. Furthermore, the serum concentrations of IgA and IgE were significantly lower in patients with CFS; however, the values were within the normal reference range.

All other variables were similar in the two groups. This study does not suggest a clearly disordered immune system or a chronic viral infection as a major pathogenetic factor in CFS. Longitudinal studies of immunological and virological parameters in CFS are warranted as are studies on patients that are severely handicapped.

Comment in: [Chronic fatigue syndrome and angiotensin-converting enzyme]. [Ugeskr Laeger. 1995]

 

Source: Rasmussen AK, Nielsen H, Andersen V, Barington T, Bendtzen K, Hansen MB, Nielsen L, Pedersen BK, Wiik A. Chronic fatigue syndrome–a controlled cross-sectional study. Ugeskr Laeger. 1994 Nov 14;156(46):6836-40. [Article in Danish] http://www.ncbi.nlm.nih.gov/pubmed/7839498

 

Psychobehavioral and immunological characteristics of adult people with chronic fatigue and patients with chronic fatigue syndrome

Abstract:

The psychobehavioral responses and cellular immune function were investigated in healthy people (control, N = 21), adult people with chronic fatigue (fatigue-non-CFS group, N = 24), and patients with chronic fatigue syndrome (CFS, N = 10).

Based on psychobehavioral responses, the fatigue-non-CFS group had low general activity levels (p < .05) and slightly depressive tendencies (p < .01) compared with the control. They had many life event stresses (p < .05) and sleep disturbances (p < .01), and they could not cope appropriately with stresses.

The fatigue-non-CFS group also showed significantly lower natural killer (NK) cell activity (p < .01) and decreased numbers of CD16+ and CD56+ cells (p < .05). Compared with the fatigue-non-CFS group, patients with CFS had higher degrees of physical fatigue (p < .01) and more life event stresses (p < .05).

They had lower general activity levels and social introversion. They were also in a depressive state. NK cell activity and the numbers of CD16+ and CD56+ cells were significantly reduced in patients with CFS (p < .01).

These findings suggest that adult people with chronic fatigue may be in an intermediate state between the healthy control and patients with CFS in terms of psychobehavioral responses and low NK cell activity. We observed three cases in such an intermediate state in whom CFS subsequently developed.

 

Source: Masuda A, Nozoe SI, Matsuyama T, Tanaka H. Psychobehavioral and immunological characteristics of adult people with chronic fatigue and patients with chronic fatigue syndrome. Psychosom Med. 1994 Nov-Dec;56(6):512-8. http://www.ncbi.nlm.nih.gov/pubmed/7871106

 

Current studies on the neurobiology of chronic fatigue syndrome

Abstract:

Cytokines are soluble mediators which are released by activated immune cells during infection and inflammation. The possibility that fatigue is mediated by the effects of cytokines on the central nervous system is supported by several converging lines of evidence: 1) infusions of cytokines to immunocompromised patients induce flu-like symptoms including fatigue and malaise; 2) peripheral and central injection of cytokines to laboratory rodents induce sickness behaviour; 3) symptoms of sickness behaviour occurring during experimental infections can be abrogated by administration of anti-cytokine treatments; 4) although many pitfalls in the detection of cytokines still exist, patients afflicted with the chronic fatigue syndrome have been found in some studies to display instances of excessive production of cytokines.

Experimental studies have confirmed that cytokines are interpreted by the brain as internal signals for sickness. Furthermore, there is evidence that sickness is a motivation which reorganizes the organism’s priorities in face of this particular threat which is represented by infectious pathogens. The elucidation of the mechanisms that are involved in these effects and in particular, the role of the cytokines which are produced in the brain in response to peripheral immune stimuli and to stressors, should give new insight on the way sickness and recovery processes are organized in the brain.

 

Source: Dantzer R. Current studies on the neurobiology of chronic fatigue syndrome. Encephale. 1994 Nov;20 Spec No 3:597-602. [Article in French] http://www.ncbi.nlm.nih.gov/pubmed/7843056

MELISA-an in vitro tool for the study of metal allergy

Abstract:

The sensitizing properties of metals widely used in medical and dental care have been studied with the help of an optimized lymphocyte proliferative assay, MELISA. MELISA (memory lymphocyte immuno-stimulation assay) was originally developed for the screening of allergenic epitopes of drugs and other chemicals of low molecular weight, but has recently been adapted for the study of metal-induced sensitization.

The patients studied suffered from various oral mucosal problems which were suspected to be caused by the release of metal ions from dental restorations. They were also troubled by chronic fatigue persisting over many years. One patient was also occupationally exposed to metals while working in a dental practice. Healthy subjects without any discomfort due to metal devices served as controls. In addition to metals used in dentistry, lymphocyte responses to organic mercurials used widely as preservatives in vaccines, eye/nose drops and contact lense fluids were studied.

The results indicated that mercurials, as well as other metals such as gold or palladium, induce strong lymphocyte proliferative responses in patients with oral or systemic symptoms, but not in similarly exposed unaffected subjects.

The results of MELISA performed with a pair of identical twins with chronic fatigue syndrome (CFS) indicated that metal-specific responses may be dependent on the genetics of the patient. Thus, many metals that are today accepted for use in medicine and dentistry carry a definite sensitizing risk for certain genetically predisposed individuals. Therefore, the use of these metals should be limited in the future.

 

Source: Stejskal VD, Cederbrant K, Lindvall A, Forsbeck M. MELISA-an in vitro tool for the study of metal allergy. Toxicol In Vitro. 1994 Oct;8(5):991-1000. http://www.ncbi.nlm.nih.gov/pubmed/20693060

 

Simultaneous measurement of antibodies to Epstein-Barr virus, human herpesvirus 6, herpes simplex virus types 1 and 2, and 14 enteroviruses in chronic fatigue syndrome: is there evidence of activation of a nonspecific polyclonal immune response?

Abstract:

As a test of the hypothesis that elevated titers of viral antibodies in patients with chronic fatigue syndrome (CFS) are due to a nonspecific polyclonal immune response, antibodies to Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6), and 14 enteroviruses in 20 patients with CFS and 20 age- and gender-matched controls were simultaneously measured.

Similarly, titers of IgG to herpes simplex virus (HSV) types 1 and 2 were measured in 18 of these cases and in the respective controls. IgG to EBV viral capsid antigen (VCA) was present at titers > or = 1:320 in 55% of cases vs. 15% of controls (P = .02).

The geometric mean titers of early antigen antibody to EBV, HHV-6 IgG, and HSV-1 and HSV-2 IgG were not significantly different among cases and controls. Of the 14 enteroviral antibodies tested for, only those to coxsackieviruses B1 and B4 were present at significant titers (> or = 1:8) in cases vs. controls (P = .02 and P = .001, respectively).

Of the cases, 19 (95%) had either an EBV VCA IgG titer > or = 1:320 or a coxsackievirus B1 or B4 antibody titer > or = 1:8, a percentage significantly higher than that of controls (40%; P = .0004). Titers of EBV VCA IgG and coxsackievirus B1 and B4 antibodies were simultaneously elevated in only 20% of cases.

There was no correlation between elevated titers of EBV VCA IgG and IgG to HHV-6, HSV-1, and HSV-2 or antibody to coxsackieviruses B1 and B4 in the cases. The prevalence of reported allergies to medications or other substances was identical in both groups (60%). These findings suggest that in the majority of cases of CFS, elevation of viral antibody titers is not due to a nonspecific polyclonal immune response.

Comment in: Viral antibodies in chronic fatigue syndrome. [Clin Infect Dis. 1995]

 

Source: Manian FA. Simultaneous measurement of antibodies to Epstein-Barr virus, human herpesvirus 6, herpes simplex virus types 1 and 2, and 14 enteroviruses in chronic fatigue syndrome: is there evidence of activation of a nonspecific polyclonal immune response? Clin Infect Dis. 1994 Sep;19(3):448-53. http://www.ncbi.nlm.nih.gov/pubmed/7811864

 

Serum concentrations of 2′,5′-oligoadenylate synthetase, neopterin, and beta-glucan in patients with chronic fatigue syndrome and in patients with major depression

Chronic fatigue syndrome is characterised by debilitating severe fatigue persisting for more than six months. Furthermore, it is associated with physical symptoms, such as mild fever, sore throat, arthralgia, and myalgia, as well as psychological symptoms such as headache, insomnia, depressive state, and neuropsychiatric symptoms. It has often been claimed that the onset of chronic fatigue syndrome follows an infection or infection-like illness; hence a certain microorganism(s) or virus may cause it. Another possible candidate for inducing chronic fatigue syndrome is cellular or humoral immune dysfunction, which has been found in patients with the disease. There is controversy also as to whether or not chronic fatigue syndrome and major depression (mood disorder) represent different entities.

Mild fever, pharyngitis, and lymphadenopathy, which are suggestive of the existence of inflammation, are often associated with chronic fatigue syndrome, but the peripheral leucocyte count, erythrocyte sedimentation rate, and C-reactive protein concentration are usually normal in patients with chronic fatigue syndrome. Hence, it is possible that certain cytokines may produce the symptoms in patients with chronic fatigue syndrome and, possibly, those with major depression. For example, interferon is known to cause fever, fatigue, and psychoneurological abnormalities. We conducted this study to clarify whether or not 2′,5′-oligoadenylate synthetase (2,5-AS), neopterin, adenosine deaminase, endotoxin, or B-glucan participate in the pathogenesis of chronic fatigue syndrome.

You can read the rest of this article here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1073106/pdf/jnnpsyc00038-0135b.pdf

 

Source: Matsuda J, Gohchi K, Gotoh N. Serum concentrations of 2′,5′-oligoadenylate synthetase, neopterin, and beta-glucan in patients with chronic fatigue syndrome and in patients with major depression. J Neurol Neurosurg Psychiatry. 1994 Aug;57(8):1015-6. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1073106/

 

Chronic fatigue syndrome–a controlled cross sectional study

Abstract:

OBJECTIVE: To look for signs of immunodeficiencies and/or longstanding infections underlying chronic fatigue syndrome (CFS).

METHODS: Twenty-one patients fulfilling the Centers for Disease Control criteria for CFS were compared to 21 age and sex matched controls. A number of viral antibodies as well as the following tests evaluating the immune system were studied: autoantibody profile, cell surface markers on isolated blood mononuclear cells, cytokine production, lymphocyte proliferative responses, natural killer cell activity and quantitation of immunoglobulin secreting cells.

RESULTS: Production in vitro of the predominantly T cell derived cytokines interleukin 2 and interferon gamma was significantly higher in patients with CFS compared to the control group. Furthermore, the serum concentrations of IgA and IgE were lower in patients with CFS; however, this difference was caused by a larger number with values of IgA and IgE above the upper limit of the normal range among the controls than among the patients with CFS. All other variables were similar in the 2 groups.

CONCLUSION: A pathogenically significant imbalance of the immune system in patients with CFS cannot be excluded. However, evidence of a causal link between abnormal immunity and CFS was not obtained.

 

Source: Rasmussen AK, Nielsen H, Andersen V, Barington T, Bendtzen K, Hansen MB, Nielsen L, Pedersen BK, Wiik A. J Rheumatol. 1994 Aug;21(8):1527-31. http://www.ncbi.nlm.nih.gov/pubmed/7983659

 

Chronic fatigue syndrome. Immunological findings vary between populations

Comment on: Longitudinal study of outcome of chronic fatigue syndrome. [BMJ. 1994]

 

Editor,-We were interested in Andrew Wilson and colleagues’ paper investigating predictors of the long term outcome of the chronic fatigue syndrome in patients in Australia. We have investigated the association between immune activation and presumed cutaneous anergy in 68 Scottish patients with the syndrome (19 cases conformed to the Centers for Disease Control’s criteria, 18 cases had been diagnosed by a consultant, 28 cases had been diagnosed by a general practitioner, and three patients referred themselves) and 22 family contacts. We assessed delayed hypersensitivity responses (using Multitest antigens and tuberculin skin tests) and evaluated peripheral blood activation markers (CD8, CD38/ CD llb/HLA-DR) using flow cytometry. Patients were classified into three groups on the basis of current severity of illness and mobility.

You can read the rest of this comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2540184/pdf/bmj00440-0055b.pdf

 

Source: Abbot NC, Spence VA, Lowe JG, Potts RC, Hassan AH, Belch JJ, Beck JS. Chronic fatigue syndrome. Immunological findings vary between populations. BMJ. 1994 May 14;308(6939):1299. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2540184/