Time marches on, they say, but sometimes it can seem to stand still, at least where research into ME/CFS is concerned!

One of the early biomedical investigations into ME/CFS occurred at the University of Dundee in 1993, spurred by an observation by Prof Jay Levy (San Francisco) that people with ME/CFS had raised levels of a particular “activation marker” on white blood cells (see report). The particular marker was CD38 (cluster of differentiation 38), a glycoprotein found on the surface of many immune cells, which is a marker of cell activation. Interestingly, the CD38 protein has subsequently been linked with HIV infection, type II diabetes mellitus and bone metabolism, as well as some genetically determined conditions – and it has also been used as a prognostic marker in leukemia. The point about Prof Levy’s observations in people with ME/CFS was that they indicated that immune activation could be associated with the illness.

The team at the University of Dundee thought they would repeat and extend these experiments by investigating the association between immune activation and delayed hypersensitivity responses (using Multitest antigens and tuberculin skin tests) in 68 people with ME/CFS and 22 family contacts, and 15 healthy people who were not contacts. They assessed 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.

An intriguing finding was that the most unwell group of people with ME/CFS had appreciably higher levels of CD8, CD38 T cells than people with ME/CFS who were less ill (Abbot et al, BMJ, May 14, 1994). But the most unexpected finding was a positive relationship (r=0.78, P<0.00002) between CD38 activation markers in patients and their close family contacts (see the graph).

 

Relation between CD8, CD38 activation markers (expressed as percentage of total lymphocyte population) in peripheral blood of patients with ME/CFS and family contacts

Relation between CD8, CD38 activation markers (expressed as percentage of total lymphocyte population) in peripheral blood of patients with ME/CFS and family contacts

These pairs were not consanguineous (17 spouses, five other family members), and it could be that the relationship could have been caused by some innocent factor in the environment. However, because CD38 level is a marker of immune activation, and is found to be raised in infections (including HIV infection), the relationship might suggest the presence of an infectious agent that affects both patients and household contacts but causes symptoms only in patients.

Like many intriguing biomedical observations on ME/CFS patients, this finding has lain unexplored in the scientific literature for years. Timescales in science can be long, however, and the time may be ripe for its rediscovery.

Reference

Abbot NC, Spence VA, Lowe JG, Potts RC, Hassan AH, Belch JJ, Beck JS. Chronic fatigue syndrome. Immunological findings vary between populations. British Medical Journal, 1994 May 14; 308(6939): 1299. (read full text)