Immunologic parameters in chronic fatigue syndrome, major depression, and multiple sclerosis


      The purpose of this study was to evaluate the immune dysfunction hypothesis of chronic fatigue syndrome (CFS) by comparing immunologic data from patients with CFS with data from patients with other fatiguing illnesses—major depression and multiple sclerosis (MS)—and with data from healthy sedentary controls. The subjects were 65 healthy sedentary controls, 71 CFS patients (41 with no axis-I diagnosis), 23 patients with mild MS, and 21 patients with major depression. Blood was sampled and assayed for the following: (1) immunologic serologic variables—circulating immune complexes (i.e., Raji cell and C1q binding), immunoglobulins A, E, G, and M, and IgG subclasses; (2) cell surface activation markers—the proportion of CD4+ cells expressing CD45RA+ and CD45RO+ and the proportion of CD8+ cells expressing CD38+, CD11b, HLA-DR+ and CD28+; and (3) natural killer (NK) total cell count as well as the proportion of lymphocytes expressing NK cell surface markers (i.e., CD3/CD16+ and CD56+. Of the 18 variables studied, differences between CFS patients and controls were found only for IgG1 and IgG3. When CFS patients were stratified by the presence or absence of concurrent axis-I disease, it was the group with axis-I disorder that had the lowest IgG1 values—contrary to expectation. When data from patients with MS and major depression were also evaluated, the subclass deficiency was no longer significant. The one group to show evidence for immune activation (i.e., an elevated proportion of CD4+ cells expressing the CD45RA+ activation marker) was the group with mild MS. These data support neither immune dysfunction nor immune activation in CFS or in major depression, for the variables studied. The reductions in IgG subclasses may be an epiphenomenon of patient or control subject composition. In contrast, MS, even in the mild and early stages, as in the patients studied here, is associated with immune activation.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to The American Journal of Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Levy J.A
        • Landay A.L
        • Jessop C
        • Lennette E
        Chronic fatigue syndrome.
        in: Root R.K Sande M.A Viral Infections Diagnosis, Treatment and Prevention. Churchill Livingstone, New York1992: 127-144
        • Lloyd A.R
        • Wakefield D
        • Boughton C.R
        • Dwyer J.M
        Immunological abnormalities in the chronic fatigue syndrome.
        Med J Aust. 1989; 151: 122-124
        • Buchwald D
        • Komaroff A.L
        Review of laboratory findings for patients with chronic fatigue syndrome.
        Rev Infect Dis. 1991; 13: S12-S18
        • Rasmussen ÅK
        • Nielsen H
        • Andersen V
        • et al.
        Chronic fatigue syndrome—a controlled cross sectional study.
        J Rheumatol. 1994; 21: 1527-1531
        • Bates D.W
        • Buchwald D
        • Lee J
        • et al.
        Clinical laboratory test findings in patients with chronic fatigue syndrome.
        Arch Intern Med. 1995; 155: 97-103
        • Landay A.L
        • Jessop C
        • Lennette E.T
        • Levy J.A
        Chronic fatigue syndrome.
        Lancet. 1991; 338: 707-712
        • Straus S.E
        • Fritz S
        • Dale J.K
        • Gould B
        • Strober W
        Lymphocyte phenotype and function in the chronic fatigue syndrome.
        J Clin Immunol. 1993; 13: 30-40
        • Gupta S
        • Vayuvegula B
        A comprehensive immunological analysis in chronic fatigue syndrome.
        Scand J Immunol. 1991; 33: 319-327
        • Fisk J.D
        • Pontefract A
        • Ritvo P.G
        • Archibald C.J
        • Murray T.J
        The impact of fatigue on patients with multiple sclerosis.
        Can J Neurol Sci. 1994; 21: 9-14
        • DeLuca J
        • Johnson S.K
        • Ellis S.P
        • Natelson B.H
        Cognitive functioning is impaired in chronic fatigue syndrome patients devoid of psychiatric disease.
        J Neurol Neurosurg Psychiatry. 1997; 62: 151-155
        • Holmes G.P
        • Kaplan J.E
        • Gantz N.M
        • et al.
        Chronic fatigue syndrome.
        Ann Intern Med. 1988; 108: 387-389
        • Fukuda K
        • Straus S.E
        • Hickie I
        • et al.
        The chronic fatigue syndrome.
        Ann Intern Med. 1994; 121: 953-959
        • Natelson B.H
        • Johnson S.K
        • DeLuca J
        • et al.
        Reducing heterogeneity in chronic fatigue syndrome.
        Clin Infect Dis. 1995; 21: 1204-1210
        • Marcus S
        • Robins L.N
        • Bucholz K
        Quick Diagnostic Interview Schedule 3R, version 1. Washington University School of Medicine, St. Louis, MO1990
        • Poser C.M
        • Paty D.W
        • Scheinberg L
        • et al.
        New diagnostic criteria for multiple sclerosis.
        Ann Neurol. 1983; 13: 227-231
        • Kurtzke J.F
        Rating of neurologic impairment in multiple sclerosis.
        Neurology. 1983; 33: 1444-1452
        • McNair D.M
        • Lorr M
        • Droppleman L.F
        Profile of Mood States. Educational and Industrial Testing Service, San Diego1971
        • Albini B
        • Fagundus A.M
        • Vladutiu A.C
        Circulating immune complexes.
        in: Atassi M.Z Van Oss C.J Absolom D.R Molecular Immunology. Marcel Dekker, New York1984: 381-401
        • Read R
        • Spickett G
        • Harvey J
        • Edwards A.J
        • Larson H.E
        IgG1 subclass deficiency in patients with chronic fatigue syndrome.
        Lancet. 1988; i: 241-242
        • Linde A
        • Smith C.I.E
        IgG subclass deficiency and chronic fatigue syndrome.
        Lancet. 1988; i: 885-886
        • Bennett A.L
        • Fagioli L.R
        • Schur P.H
        • Schacterle R.S
        • Komaroff A.L
        Immunoglobulin subclass levels in chronic fatigue syndrome.
        J Clin Immunol. 1996; 16: 315-320
        • Natelson B.H
        • Ellis S.P
        • O’Braoáin P.J
        • DeLuca J
        • Tapp W.N
        Frequency of deviant immunological test values in chronic fatigue syndrome patients.
        Clin Diagn Lab Immunol. 1995; 2: 238-240
        • Vollmer-Conna U
        • Hickie I
        • Hadzi-Pavlovic D
        • et al.
        Intravenous immunoglobulin is ineffective in the treatment of patients with chronic fatigue syndrome.
        Am J Med. 1997; 103: 38-43
        • Ho-Yen D.O
        • Billington R.W
        • Urquhart J
        Natural killer cells and the post viral fatigue syndrome.
        Scand J Infect Dis. 1991; 23: 711-716
        • Swanink C.M.A
        • Vercoulen J.H.M.M
        • Galama J.M.D
        • et al.
        Lymphocyte subsets, apoptosis, and cytokines in patients with chronic fatigue syndrome.
        J Infect Dis. 1996; 173: 460-463
        • 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; 82: 83-91
        • Mawle A.C
        • Nisenbaum R
        • Dobbins J.G
        • et al.
        Immune responses associated with chronic fatigue syndrome.
        J Infect Dis. 1997; 175: 136-141
        • Shephard R.J
        • Rhind S
        • Shek P.N
        Exercise and the immune system.
        Sports Med. 1994; 18: 340-369
        • Pedersen B.K
        • Ullum H
        NK cell response to physical activity.
        Med Sci Sports Exerc. 1994; 26: 140-146
        • Pepper C.M
        • Krupp L.B
        • Friedberg F
        • Doscher C
        • Coyle P.K
        A comparison of neuropsychiatric characteristics in chronic fatigue syndrome, multiple sclerosis, and major depression.
        J Neuropsychiatry Clin Neurosci. 1993; 5: 200-205
        • Komaroff A.L
        • Fagioli L.R
        • Geiger A.M
        • et al.
        An examination of the working case definition of chronic fatigue syndrome.
        Am J Med. 1996; 100: 56-64
        • Rohowsky-Kochan C
        • Eiman D
        • Troiano R
        • et al.
        Decreased suppressor-inducer T lymphocytes in multiple sclerosis and other neurological diseases.
        J Neurol Sci. 1990; 28: 161-166
        • Maes M
        • Lambrechts J
        • Bosmans E
        • et al.
        Evidence for a systemic immune activation during depression.
        Psychol Med. 1992; 22: 45-53
        • Tukey J.W
        Exploratory Data Analysis. Addison-Wesley, Reading, MA1977