Immunological findings may vary between populations
Mr Bob Potts
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 (1). We have investigated the association between immune activation (2) and presumed cutaneous anergy (3) 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/CD11b/HLA-DR) using flow cytometry. Patients were classified into three groups on the basis of current severity of illness and mobility.
In our patients anergy shown by the Multitest (defined in the same manner as Wilson and colleagues defined it) and by the tuberculin skin test was not a prominent feature in any of the groups of subjects, including the most unwell. The most unwell, however, exhibited appreciably higher levels of CD8, CD38 T cells than the other groups of patients. In the 65 patients fit enough to have the Multitest anergic, hypoanergic, and normal responses were shown by 3% (n=2), 25% (16) and 72% (47) of patients respectively. This compares with 6% (1), 39% (7), and 56% (10) respectively of the 18 family contacts tested and with 7% (1), 20% (3), and 73% (11) of 15 healthy people who were not contacts. The rate of positive responses to the tuberculin skin test was as high in the patients with the chronic fatigue syndrome (79% (51/65)) as in household contacts (83 (15/18)), and these positive responses showed conventional hyperaemic and gas transport changes (4).
In view of these findings, cutaneous anergy must not be viewed as a conspicuous feature of Scottish patients with the chronic fatigue syndrome. In addition, our finding of ‘hypoanergy’ (2–4 mm induration in women, 2–9 mm induration in men (1)) in control groups suggests differences in immunisation or exposure to antigens between this healthy population and those in the United States or Australia. Perhaps ‘normal’ ranges for responses to the Multitest should be defined locally to aid the assessment of delayed hypersensitivity responses in patients.
Our most unexpected finding was a positive relation (r=0.78, p<0.00002) between CD38 activation markers in patients and their close family contacts (figure). These pairs were not consanguineous (17 spouses, five other family members), and this relation could have an environmental basis. In view of the association of these markers with progression of HIV infection (5), however, they may also have potential in predicting outcome in patients with the chronic fatigue syndrome.
References
- Wilson A, Hickie I, Lloyd A, Hadzi-Pavlovic D, Boughton C, Dwyer J et al. Longitudinal study of outcome of chronic fatigue syndrome. BMJ 1994; 308: 756–9.
- Levy JA, Jessop C, Landay AL, Lennette E. Chronic fatigue syndrome: is it a state of chronic immune activation against an infectious virus? In: Root RK, Sande MA, eds. Contemporary issues in infectious diseases. Vol 10. New York: Churchill Livingstone, 1993.
- Lloyd A, Hickie I, Hickie C, Dwyer J, Wakefield D. Cellmediated immunity in patients with chronic fatigue syndrome, healthy control subjects and patients with major depression. Clin Exp Immunol 1992; 87: 76–9.
- Abbot NC, Beck JS, Carnochan FM, Lowe JG, Gibbs JH. Circulatory adaptation to the increased metabolism in the skin at the site of the tuberculin reaction. Int J Microcirc Clin Exp 1992; 11: 383–401.
- Levacher M, Hulstaert F, Tallet S, Ullery S, Pocidalo JJ, Bach BA. The significance of activation markers on CD8 lymphocytes in human immunodeficiency syndrome: staging and prognostic value. Clin Exp Immunol 1992; 90: 376–82.
Funding
This work was funded by the Chief Scientist Organisation of the Scottish Home and Health Department, and began a process of investigation which eventually led to the founding of ME Research UK.
Publication
Abbot NC, Spence VA, Lowe JG, Potts RC, Hassan AHA, Belch JJF, Beck JS. Immunological findings may vary between populations. BMJ 1994; 308: 1297–301.
