Evidence for the Presence of Immune Dysfunction in Chronic Fatigue Syndrome

Abstract

Chronic fatigue syndrome is a medically unexplained ailment characterized by new onset of fatigue accompanied by rheumatological, infectious, and neuropsychiatric symptoms. Because the ailment often begins suddenly with a flu-like presentation, early pathophysiological ideas as to cause included viral infection and immune activation. When early reports identified putative immunological abnormalities in this illness, it was given the name of chronic fatigue and immune dysfunction syndrome, or CFIDS.The purpose of this review is to evaluate the immunological literature to determine if strong evidence to support this notion exists. We collected and reviewed 239 published papers, of which only 72 fulfilled a set of criteria for use in this review. For this review, we developed the following criteria: papers had to be published in the peer review literature; patients had to be from a group with substantial fatigue lasting at least 6 months (the vast majority fulfilled either the 1988 [21] or the 1994 [13] case definition of chronic fatigue syndrome [CFS]); papers had to compare CFS patients to healthy controls; and actual data had to be shown with evidence of testing for statistical significance. So, for example, when a paper reported no difference between patients and controls for some immunological variables but actual data were not included, we did not include it. Also, if a report compared patient data to normative values rather than to the study's own control group, we did not include it.The numbers of immunologically active cells and immunologically active substances such as cytokines reported in the literature have mushroomed in the past decade. To keep this review manageable, we are reporting scientific papers only on those variables for which either consistent or inconsistent abnormalities were reported by more than one group. We did not review papers reporting immunological variables to be within normal limits but have listed those studies in which more than one group found such results in a table. We have chosen not to list those variables reported abnormal in only one study because those results have not yet been replicated. When inconsistent results among laboratories were found for any immunological variable, we reviewed the methods described in those papers in an effort to identify reasons for such discrepancies.Note: when a group published more than one paper and it was apparent that the two studies used many if not all of the patients whose data are in the second paper, we chose to include only the more recent paper or the one with the largest number of subjects. To provide several examples, Tirelli published two papers, the first with 205 subjects and the second with 265 patients (66, 67). When data from one variable appeared in both papers, we included data from only the latter. Our own group has published three papers using different statistical methods and making different comparisons when reviewing lymphocyte populations. Thus, we used the one paper that controlled for multiple comparisons (74)...

Spinal Fluid Abnormalities in Patients with Chronic Fatigue Syndrome

“…However, two groups have reviewed the literature and have concluded that insufficient evidence exists to support that hypothesis (14,16). If some CFS patients had an unrecognized encephalopathy, we reasoned that we might find evidence for immune dysfunction in spinal fluid.…”

“…In two plasma cytokine studies using classical statistical methods, we found no differences in immune variables between CFS patients and sedentary, age-and sex-matched controls (10,17). In fact, a recent comprehensive analysis of all controlled studies on immune function in CFS found little evidence to support the immune dysfunction hypothesis (16).…”

Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: An Update

“…Investigations into a possible autoimmune component in CFS have shown an increase in the number of B cells of the CD20lCD5 phenotype (7) -a situation normally associated with the production of autoantibodies -and, in the same group of patients, an increase in the expression of CD2 ligand for retroviruses (8). In a 1996 study, 52% of patients with CFS were found to produce autoantibodies directed against nuclear components (9-10).…”

Cytokines across the Night in Chronic Fatigue Syndrome with and without Fibromyalgia

“…Two findings fostered this idea: first, approximately a third of CFS patients report a sudden, influenza-like onset of their illness (37), and second, administration of proinflammatory cytokines leads to many of the same symptoms seen in CFS (26). However, we recently reviewed the literature on this hypothesis and found relatively little empirical data to support it (20); a more recent small study did report higher levels of one such cytokine, serum transforming growth factor ␤, in patients than in controls (35); however, another group did not confirm this result (30). Other work extending the research to cellular production of proinflammatory cytokines was also negative (1).…”