Immunological and psychological dysfunction in patients receiving immunotherapy for chronic fatigue syndrome

Abstract:

Associations between immunological and psychological dysfunction in 33 patients with Chronic Fatigue Syndrome (CFS) were examined before and in response to treatment in a double blind, placebo-controlled trial of high dose intravenous immunoglobulin. Only those patients who received active immunotherapy demonstrated a consistent pattern of correlations between improvement in depressive symptoms and markers of cell-mediated immunity (CMI).

This finding lends some support to the hypothesis that depressive symptoms in patients with CFS occur secondary to, or share a common pathophysiology with, immunological dysfunction. This pattern and the lack of strong associations between depression and immunological disturbance prior to treatment are less supportive of the view that CFS is primarily a form of depressive disorder or that immunological dysfunction in patients with CFS is secondary to concurrent depression.

 

Source: Hickie I, Lloyd A, Wakefield D. Immunological and psychological dysfunction in patients receiving immunotherapy for chronic fatigue syndrome. Aust N Z J Psychiatry. 1992 Jun;26(2):249-56. http://www.ncbi.nlm.nih.gov/pubmed/1642616

 

Pain syndromes, disability, and chronic disease in childhood

Abstract:

Childhood disability and chronic disease are common, and their prevalence is increasing as children survive with conditions that were previously fatal. It is important that physicians in training learn about disability and handicap, and the functioning of multidisciplinary teams to manage these problems. Chronic ill-health is often very expensive to manage, and some serious and creative thinking about the best way to fund such health care is urgently needed.

Pediatric rheumatologists are involved with the care of many children with chronic and recurrent musculoskeletal pain; however, they have not perhaps focused enough research effort on the investigation of pain and its management. Whether reflex neurovascular dystrophy, fibromyalgia, and chronic fatigue syndrome are part of a disease continuum is unclear, but it seems probable that psychosocial problems are often important contributing factors in all three conditions.

Immunoglobulin subclass deficiencies are being increasingly delineated, occurring in chronic fatigue syndrome as well as many other disease states. Their clinical relevance still remains, for the most part, uncertain. Short stature occurs in many chronic illnesses, and the role of growth hormone treatment in these conditions is beginning to be investigated.

 

Source: Malleson PN. Pain syndromes, disability, and chronic disease in childhood. Curr Opin Rheumatol. 1991 Oct;3(5):860-6. http://www.ncbi.nlm.nih.gov/pubmed/1836344

 

Altered cytokine release in peripheral blood mononuclear cell cultures from patients with the chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is an idiopathic illness associated with a variety of immunologic abnormalities. To investigate potential pathogenetic mechanisms, we evaluated serum levels and peripheral blood mononuclear cell (PBMC) production of selected cytokines and immunoglobulins.

Serum bioactive transforming growth factor beta (TGF-beta) levels were higher (P less than 0.01) in patients with CFS (290 +/- 46 pg/mL) than in control subjects (104 +/- 18 pg/mL), but levels of other cytokines tested were not different. Lipopolysaccharide-stimulated release of interleukin 1 beta (IL-1 beta), IL-6, and tumor necrosis factor-alpha was increased (P less than 0.05) in PBMC cultures from patients with CFS versus control subjects; enhanced (P less than 0.01) IL-6 release to phytohemagglutinin was also observed.

In contrast, TGF-beta release in response to lipopolysaccharide was depressed (P less than 0.01) in PBMC cultures derived from patients with CFS. No differences in IL-2 and IL-4 or immunoglobulin production were observed.

The enhanced release of inflammatory cytokines by stimulated PBMC from patients with CFS suggests that these cells are primed for an increased response to immune stimuli. These data also suggest an association between abnormal regulation of TGF-beta production in vivo and in vitro with the immunologic consequence of CFS.

 

Source: Chao CC1, Janoff EN, Hu SX, Thomas K, Gallagher M, Tsang M, Peterson PK. Altered cytokine release in peripheral blood mononuclear cell cultures from patients with the chronic fatigue syndrome. Cytokine. 1991 Jul;3(4):292-8. http://www.ncbi.nlm.nih.gov/pubmed/1873478

 

Postinfectious chronic fatigue syndrome: case history of thirty-five patients in Germany

Abstract:

Thirty-five patients with chronic fatigue syndrome according to the criteria of Holmes were followed for periods of up to eight years. The most frequent symptoms were severe fatigue, arthralgias and myalgias, recurrent oropharyngitis and various psychiatric disorders.

More than half of the patients suffered from neuropathy, lymphadenopathy, gastrointestinal complaints and recurrent low-grade fever. Recurrent or persistent activity of human herpesvirus -6 infection was seen in 73% of the patients and of Epstein-Barr virus in 34.4%. In addition, various other infections were diagnosed at lower frequency.

Initial routine immunologic screening revealed various types of deficiencies, these were yet inconsistent and variable when different patients were compared with each other. Tentative treatments included in immunoglobulins, nonspecific immunostimulation and virostatic drugs. No consistently positive results were obtained with any treatment schedule although immunoglobulins appeared the most efficient measure. In addition, psychologic care of the patients is indicated, since disturbances in the psycho-neuroimmunologic regulation may play a significant role in the pathogenesis of the disease.

 

Source: Hilgers A, Krueger GR, Lembke U, Ramon A. Postinfectious chronic fatigue syndrome: case history of thirty-five patients in Germany. In Vivo. 1991 May-Jun;5(3):201-5. http://www.ncbi.nlm.nih.gov/pubmed/1893076

 

Review of laboratory findings for patients with chronic fatigue syndrome

Abstract:

Various abnormalities revealed by laboratory studies have been reported in adults with chronic fatigue syndrome. Those most consistently reported include depressed natural killer cell function and reduced numbers of natural killer cells; low levels of circulating immune complexes; low levels of several autoantibodies, particularly antinuclear antibodies and antithyroid antibodies; altered levels of immunoglobulins; abnormalities in number and function of lymphocytes; and modestly elevated levels of two Epstein-Barr virus-related antibodies, immunoglobulin G to viral capsid antigen and to early antigen.

 

Source: Buchwald D, Komaroff AL. Review of laboratory findings for patients with chronic fatigue syndrome. Rev Infect Dis. 1991 Jan-Feb;13 Suppl 1:S12-8. http://www.ncbi.nlm.nih.gov/pubmed/1902321

 

A controlled trial of intravenous immunoglobulin G in chronic fatigue syndrome

Abstract:

PURPOSE: Currently, there is no established therapy for chronic fatigue syndrome (CFS), a recently defined illness that has been associated with a variety of immunologic abnormalities. Based on the hypothesis that a chronic viral infection or an immunoregulatory defect is involved in the pathogenesis of CFS, the therapeutic benefit of intravenous immunoglobulin G (IV IgG) was evaluated in a group of patients with CFS. Additionally, serum immunoglobulin concentrations and peripheral blood lymphocyte subset numbers were measured at the outset of the study, and the effect of IV IgG therapy on IgG subclass levels was determined.

PATIENTS AND METHODS: Thirty patients with CFS were enrolled in a double-blind, placebo-controlled trial of IV IgG. The treatment regimen consisted of IV IgG (1 g/kg) or intravenous placebo (1% albumin solution) administered every 30 days for 6 months. Participants completed a self-assessment form prior to each of the six treatments, which was used to measure severity of symptoms, functional status, and health perceptions. Patients were also asked to report adverse experiences defined as worsening of symptoms occurring within 48 hours of each treatment.

RESULTS: Twenty-eight patients completed the trial. At baseline, all 28 patients complained of moderate to severe fatigue, and measures of social functioning and health perceptions showed marked impairment. Low levels of IgG1 were found in 12 (42.9%), and 18 (64.3%) had low levels of IgG3. At the end of the study, no significant therapeutic benefit could be detected in terms of symptom amelioration or improvement in functional status, despite restoration of IgG1 levels to a normal range. Major adverse experiences were observed in 20% of both the IV IgG and placebo groups.

CONCLUSION: The results of this study indicate that IV IgG is unlikely to be of clinical benefit in CFS. In addition to the ongoing need for placebo-controlled trials of candidate therapies for CFS, an expanded research effort is needed to define the etiology and pathogenesis of this disorder.

Comment in:

Intravenous immunoglobulin treatment for the chronic fatigue syndrome. [Am J Med. 1990]

 

Source: Peterson PK, Shepard J, Macres M, Schenck C, Crosson J, Rechtman D, Lurie N. A controlled trial of intravenous immunoglobulin G in chronic fatigue syndrome. Am J Med. 1990 Nov;89(5):554-60. http://www.ncbi.nlm.nih.gov/pubmed/2239975

 

A double-blind, placebo-controlled trial of intravenous immunoglobulin therapy in patients with chronic fatigue syndrome

Abstract:

PURPOSE: The chronic fatigue syndrome (CFS) is characterized by profound fatigue, neuropsychiatric dysfunction, and frequent abnormalities in cell-mediated immunity. No effective therapy is known.

PATIENTS AND METHODS: Forty-nine patients (40 with abnormal cell-mediated immunity) participated in a randomized, double-blind, placebo-controlled trial to determine the effectiveness of high-dose intravenously administered immunoglobulin G. The patients received three intravenous infusions of a placebo solution or immunoglobulin at a dose of 2 g/kg/month. Assessment of the severity of symptoms and associated disability, both before and after treatment, was completed at detailed interviews by a physician and psychiatrist, who were unaware of the treatment status. In addition, any change in physical symptoms and functional capacity was recorded using visual analogue scales, while changes in psychologic morbidity were assessed using patient-rated indices of depression. Cell-mediated immunity was evaluated by T-cell subset analysis, delayed-type hypersensitivity skin testing, and lymphocyte transformation with phytohemagglutinin.

RESULTS: At the interview conducted by the physician 3 months after the final infusion, 10 of 23 (43%) immunoglobulin recipients and three of the 26 (12%) placebo recipients were assessed as having responded with a substantial reduction in their symptoms and recommencement of work, leisure, and social activities. The patients designated as having responded had improvement in physical, psychologic, and immunologic measures (p less than 0.01 for each).

CONCLUSION: Immunomodulatory treatment with immunoglobulin is effective in a significant number of patients with CFS, a finding that supports the concept that an immunologic disturbance may be important in the pathogenesis of this disorder.

Comment in:

Intravenous immunoglobulin treatment for the chronic fatigue syndrome. [Am J Med. 1990]

Immunoglobulin treatment for chronic fatigue syndrome. [Am J Med. 1991]

Intravenous immunoglobulin treatment of chronic fatigue syndrome. [Am J Med. 1991]

Placebo responses in patients complaining of chronic fatigue. [Am J Med. 1991]

 

Source: Lloyd A, Hickie I, Wakefield D, Boughton C, Dwyer J. A double-blind, placebo-controlled trial of intravenous immunoglobulin therapy in patients with chronic fatigue syndrome.  Am J Med. 1990 Nov;89(5):561-8. http://www.ncbi.nlm.nih.gov/pubmed/2146875

 

Immunological abnormalities in the chronic fatigue syndrome

Abstract:

The chronic fatigue syndrome is a disorder of unknown aetiology which is characterized by debilitating fatigue. Recent evidence has suggested that viruses may persist in the tissues of patients with chronic fatigue syndrome. A concurrent immunological disturbance is likely to be associated with the persistence of viral antigens.

Therefore, the humoral and cellular immunity of 100 patients who were suffering from chronic fatigue syndrome and that of 100 healthy, age- and sex-matched control subjects were compared. This study documents the frequent occurrence of abnormalities within the cellular and humoral immune systems of patients with well-defined chronic fatigue syndrome. Disordered immunity may be central to the pathogenesis of chronic fatigue syndrome.

In patients with chronic fatigue syndrome, a significant (P less than 0.01) reduction was found in the absolute number of peripheral blood lymphocytes in the total T-cell (CD2), the helper/inducer T-cell (CD4) and the suppressor/cytotoxic T-cell (CD8) subsets. A significant (P less than 0.001) reduction also was found in T-cell function, which was measured: in vivo by delayed-type hypersensitivity skin-testing (reduced responses were recorded in 50 [88%] of 57 patients); and in vitro by phytohaemagglutinin stimulation. Reduced immunoglobulin (Ig) levels were common (56% of patients), with the levels of serum IgG3- and IgG1-subclasses particularly (P less than 0.05) affected.

 

Source: Lloyd AR, Wakefield D, Boughton CR, Dwyer JM. Immunological abnormalities in the chronic fatigue syndrome. Med J Aust. 1989 Aug 7;151(3):122-4. http://www.ncbi.nlm.nih.gov/pubmed/2787888