Category: Immune System

Elevation of bioactive transforming growth factor-beta in serum from patients with chronic fatigue syndrome

Abstract:

The level of bioactive transforming growth factor-beta (TGF-beta) was measured in serum from patients with chronic fatigue syndrome (CFS), healthy control subjects, and patients with major depression, systemic lupus erythematosis (SLE), and multiple sclerosis (MS) of both the relapsing/remitting (R/R) and the chronic progressive (CP) types.

Patients with CFS had significantly higher levels of bioactive TGF-beta levels compared to the healthy control major depression, SLE, R/R MS, and CP MS groups (P < 0.01). Additionally, no significant differences were found between the healthy control subjects and any of the disease comparison groups.

The current finding that TGF-beta is significantly elevated among patients with CFS supports the findings of two previous studies examining smaller numbers of CFS patients.

In conclusion, TGF-beta levels were significantly higher in CFS patients compared to patients with various diseases known to be associated with immunologic abnormalities and/or pathologic fatigue. These findings raise interesting questions about the possible role of TGF-beta in the pathogenesis of CFS.

 

Source: Bennett AL, Chao CC, Hu S, Buchwald D, Fagioli LR, Schur PH, Peterson PK, Komaroff AL. Elevation of bioactive transforming growth factor-beta in serum from patients with chronic fatigue syndrome. J Clin Immunol. 1997 Mar;17(2):160-6. http://www.ncbi.nlm.nih.gov/pubmed/9083892

 

High frequency of autoantibodies to insoluble cellular antigens in patients with chronic fatigue syndrome

Abstract:

OBJECTIVE: To elucidate the humoral immune response in patients with chronic fatigue syndrome (CFS), by identification and characterization of autoantibodies.

METHODS: Initial immunofluorescence histochemistry studies of sera using human HEp-2 cell substrate were followed by antibody class subtyping and colocalization studies with reference antibodies. Association of CFS autoantigens with insoluble cellular components was determined by in situ extraction of soluble components and subsequent immunofluorescence histochemistry studies on the extracted cell substrate.

RESULTS: Of 60 CFS patients, 41 (68%) were positive for antinuclear antibodies. Localization of nuclear staining was found at the nuclear envelope (52%), in reticulated speckles (25%), in nucleoli (13%), and in dense fine speckles (5%). Twenty-eight CFS sera (47%) also had antibodies to cytoplasmic antigens. The major cytoplasmic staining pattern was of the intermediate filament type (35%). The observed nuclear envelope pattern of staining co-localized with lamina-associated polypeptide 2 (an integral nuclear membrane protein), the reticulated speckle pattern co-localized with non-small nuclear RNP splicing factor SC-35, and the intermediate filament pattern co-localized with vimentin. The intermediate filament antigen was shown to be vimentin in immunoblotting experiments using recombinant human vimentin, and one of the nuclear envelope antigens was shown previously to be lamin B1. Fifty of the 60 CFS patients (83%) had antibodies to one or another of these antigens, all of which are relatively insoluble cellular antigens, whereas a control group of patients without chronic fatigue had a significantly lower frequency of such antibodies (17%).

CONCLUSION: The high frequency of autoantibodies to insoluble cellular antigens in CFS represents a unique feature which might help to distinguish CFS from other rheumatic autoimmune diseases.

Comment in: Incidence of antinuclear antibodies in Japanese patients with chronic fatigue syndrome. [Arthritis Rheum. 1997]

 

Source: von Mikecz A, Konstantinov K, Buchwald DS, Gerace L, Tan EM. High frequency of autoantibodies to insoluble cellular antigens in patients with chronic fatigue syndrome. Arthritis Rheum. 1997 Feb;40(2):295-305. http://www.ncbi.nlm.nih.gov/pubmed/9041942

 

Markers of inflammation and immune activation in chronic fatigue and chronic fatigue syndrome

Abstract:

OBJECTIVE: Chronic fatigue syndrome (CFS) has been hypothesized to result from immune activation. We examined the role of serum markers of inflammation and immune activation among patients with CFS and in those with chronic fatigue (CF) not meeting the case definition.

METHODS: Assays for soluble interleukin 2 (IL-2) receptor, IL-6, C-reactive protein, beta 2-microglobulin, and neopterin were performed in 153 fatigued patients in a referral clinic. Patients were classified according to whether they met criteria for CFS, reported onset of illness with a viral syndrome or had a temperature > 37.5 degrees C on examination.

RESULTS: Compared to control subjects, mean concentrations of C-reactive protein, beta 2-microglobulin, and neopterin were higher in patients with CFS (p < or = 0.01) and CF (p < or = 0.01). Results did not distinguish CFS from CF. IL-6 was elevated among febrile patients compared to those without this finding (p < or = 0.001), but other consistent differences between patient subgroups were not observed. The presence of several markers was highly correlated (p < 0.01).

CONCLUSION: Our findings that levels of several markers were significantly correlated points to a subset of patients with immune system activation. Whether this phenomenon reflects an intercurrent, transient, common condition, such as an upper respiratory infection, or is the result of an ongoing illness associated process is unknown. Overall, serum markers of inflammation and immune activation are of limited diagnostic usefulness in the evaluation of patients with CFS and CF.

 

Source: Buchwald D, Wener MH, Pearlman T, Kith P. Markers of inflammation and immune activation in chronic fatigue and chronic fatigue syndrome. J Rheumatol. 1997 Feb;24(2):372-6. http://www.ncbi.nlm.nih.gov/pubmed/9034999

 

Cytokine production by adherent and non-adherent mononuclear cells in chronic fatigue syndrome

Abstract:

It has been suggested that cytokines play a role in certain clinical manifestations of chronic fatigue syndrome (CFS). In this study adherent (monocytes) and non-adherent (lymphocytes) mononuclear cells were stimulated in the presence or absence of phytohemagglutinin (PHA) or lipopolysaccharide (LPS), respectively, and supernatants were assayed for IL-6, TNF-alpha, and IL-10 by ELISA. IL-6 was also measured at the mRNA level by polymerase chain reaction.

The levels of spontaneously (unstimulated) produced TNF-alpha by non-adherent lymphocytes and spontaneously produced IL-6 by both adherent monocytes and non-adherent lymphocytes were significantly increased as compared to simultaneously studied matched controls. The abnormality of IL-6 was also observed at mRNA level.

In contrast, spontaneously produced IL-10 by both adherent and non-adherent cells and by PHA-activated non-adherent cells were decreased. This preliminary study suggests that an aberrant production of cytokines in CFS may play a role in the pathogenesis and in some of the clinical manifestations of CFS.

 

Source: Gupta S, Aggarwal S, See D, Starr A. Cytokine production by adherent and non-adherent mononuclear cells in chronic fatigue syndrome. J Psychiatr Res. 1997 Jan-Feb;31(1):149-56. http://www.ncbi.nlm.nih.gov/pubmed/9201656

 

Gender differences in host defense mechanisms

Abstract:

Extensive studies in both humans and animals have shown that females express enhanced levels of immunoreactivity compared to males. Whereas this provides females with increased resistance to many types of infection, it also makes them more susceptible to autoimmune diseases. This review will focus on gender-related differences in non-specific host defense mechanisms with a particular emphasis on monocyte/macrophage function and a primary product of monocytes: interleukin-1 (IL-1). Immunomodulatory cytokines such as IL-1 are influenced by gender-sensitive hormones, and reciprocally, these cytokines influence gender-specific hormones and tissues. Patients with chronic fatigue syndrome (CFS) are predominantly women, therefore it may be useful to look toward gender-specific differences in immune function to find a key for this poorly understood syndrome.

 

Source: Cannon JG, St Pierre BA. Gender differences in host defense mechanisms. J Psychiatr Res. 1997 Jan-Feb;31(1):99-113. http://www.ncbi.nlm.nih.gov/pubmed/9201652

 

In vitro effects of echinacea and ginseng on natural killer and antibody-dependent cell cytotoxicity in healthy subjects and chronic fatigue syndrome or acquired immunodeficiency syndrome patients

Abstract:

Extracts of Echinacea purpurea and Panax ginseng were evaluated for their capacity to stimulate cellular immune function by peripheral blood mononuclear cells (PBMC) from normal individuals and patients with either the chronic fatigue syndrome or the acquired immunodeficiency syndrome.

PBMC isolated on a Ficoll-hypaque density gradient were tested in the presence or absence of varying concentrations of each extract for natural killer (NK) cell activity versus K562 cells and antibody-dependent cellular cytotoxicity (ADCC) against human herpesvirus 6 infected H9 cells. Both echinacea and ginseng, at concentrations > or = 0.1 or 10 micrograms/kg, respectively, significantly enhanced NK-function of all groups. Similarly, the addition of either herb significantly increased ADCC of PBMC from all subject groups.

Thus, extracts of Echinacea purpurea and Panax ginseng enhance cellular immune function of PBMC both from normal individuals and patients with depressed cellular immunity.

 

Source: See DM, Broumand N, Sahl L, Tilles JG. In vitro effects of echinacea and ginseng on natural killer and antibody-dependent cell cytotoxicity in healthy subjects and chronic fatigue syndrome or acquired immunodeficiency syndrome patients. Immunopharmacology. 1997 Jan;35(3):229-35. http://www.ncbi.nlm.nih.gov/pubmed/9043936

 

Chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) has emerged as a public health concern over the past decade. A working case definition was created in 1988 and revised in 1994, and this has been used to establish prevalence estimates using physician-based surveillance and an a random digit dial telephone survey. Although CFS has some characteristics of an infectious disease, so far no infectious agent has been associated with the illness. Studies of immune function in CFS patients failed to detect differences between cases and healthy controls. However, when cases were subgrouped according to whether they had a sudden or gradual onset, differences in immunologic markers were detected between cases and their matched controls.

 

Source: Mawle AC. Chronic fatigue syndrome. Immunol Invest. 1997 Jan-Feb;26(1-2):269-73. http://www.ncbi.nlm.nih.gov/pubmed/9037629

 

Clinical improvement in chronic fatigue syndrome is not associated with lymphocyte subsets of function or activation

Abstract:

The relationship between markers of immune function and chronic fatigue syndrome (CFS) is controversial. To examine the relationship directly, 43 subjects with CFS entering a randomized controlled trial of a nonpharmacological treatment for CFS gave samples for immunological analysis before and after treatment. Percentage levels of total CD3+ T cells, CD4 T cells, CD8 T cells, and activated subsets did not differ between CFS subjects and controls. Naive (CD45RA+ RO-) and memory (CD45RA- RO+) T cells did not differ between subjects and controls.

Natural killer cells (CD16+/CD56+/CD3-) were significantly increased in CFS patients compared to controls, as was the percentage of CD11b+ CD8 cells.

There were no correlations between any immune variable and measures of clinical status, with the exception of a weak correlation between total CD4 T cells and fatigue. There was a positive correlation between memory CD4 and CD8 T cells and depression scores and a negative correlation between naive CD4 T cells and depression.

No immune measures changed during the course of the study, and there was no link between clinical improvement as a result of the treatment program and immune status. Immune measures did not predict response or lack of response to treatment.

In conclusion, we have been unable to replicate previous findings of immune activation in CFS and unable to find any important associations between clinical status, treatment response, and immunological status.

 

Source: Peakman M, Deale A, Field R, Mahalingam M, Wessely S. Clinical improvement in chronic fatigue syndrome is not associated with lymphocyte subsets of function or activation. Clin Immunol Immunopathol. 1997 Jan;82(1):83-91. http://www.ncbi.nlm.nih.gov/pubmed/9000046

 

Immune responses associated with chronic fatigue syndrome: a case-control study

Abstract:

An exploratory case-control study was conducted to assess whether the many reported differences in the immune function of chronic fatigue syndrome (CFS) patients are detectable in rigorously defined cases of CFS. Although many studies have reported differences between cases and controls in various measures of immune function, none of these differences were found in all studies.

In this study, no differences were found in white blood cell numbers; immune complex, complement, or serum immunoglobulin levels; delayed type hypersensitivity and allergic responses; NK cell function; and proliferative responses to mitogens and antigens. Marginal differences were detected in cytokine responses and in cell surface markers in the total CFS population.

However, when the patients were subgrouped by type of disease onset (gradual or sudden) or by how well they were feeling on the day of testing, more pronounced differences were seen

 

Source: Mawle AC, Nisenbaum R, Dobbins JG, Gary HE Jr, Stewart JA, Reyes M, Steele L, Schmid DS, Reeves WC. Immune responses associated with chronic fatigue syndrome: a case-control study. J Infect Dis. 1997 Jan;175(1):136-41. http://jid.oxfordjournals.org/content/175/1/136.long (Full article)

 

Immunoglobulin subclass levels in chronic fatigue syndrome

Abstract:

The levels of immunoglobulin subclasses were determined for 46 patients meeting the original Centers for Disease Control case definition of chronic fatigue syndrome and were compared to values obtained for 50 age- and gender-matched healthy volunteer blood donor controls. The levels of immunoglobulin subclasses in these groups were further compared to a third group of additional chronic fatigue syndrome cases from whom samples had been obtained and frozen prospectively over a period of 7 years. These data do not demonstrate significant immunoglobulin subclass deficiencies in patients with chronic fatigue syndrome.

 

Source: Bennett AL, Fagioli LR, Schur PH, Schacterle RS, Komaroff AL. Immunoglobulin subclass levels in chronic fatigue syndrome. J Clin Immunol. 1996 Nov;16(6):315-20. http://www.ncbi.nlm.nih.gov/pubmed/8946275