Confirmatory study of gene expression in peripheral blood of patients with Gulf War Syndrome

Dr Jonathan R Kerr

Gulf War Syndrome (GWS) is a constellation of symptoms which were reported with a significant incidence in military personnel who fought in the first Gulf War. The most frequent complaints among veterans are fatigue, rashes, joint pains, muscle pains, neuropsychiatric complaints, shortness of breath, sleep disturbances and gastrointestinal problems. Various triggers and mechanisms have been proposed, and it has been shown that the symptoms in veterans with GWS are associated with cellular immune activation though the precise abnormalities remain to be determined and alternative approaches are urgently needed.

There is controversy surrounding this illness, and the situation has clear parallels with Chronic Fatigue Syndrome (CFS). These syndromes exhibit similar symptoms and Gulf War Syndrome patients often also fulfil the CDC criteria for diagnosis of CFS (Fukuda et al, 1994). In addition, they probably have aetiologic triggers and disease mechanisms in common; for example, both illnesses diseases have a Th2 lymphocyte response. Importantly, both Gulf War Syndrome and ME/CFS exhibit indisputable organic and biological abnormalities, and these must be characterised.

Dr Kerr’s team has performed a pilot study of gene expression in CFS patients compared with controls (Kaushik et al, 2005) and has demonstrated marked human gene dysregulation, principally affecting the immune system.

The aim of this confirmatory study is therefore to elucidate the pathogenesis of Gulf War Syndrome through characterisation of human gene expression and protein analysis in 25 Gulf War Syndrome patients and 25 matched healthy blood donors, and to determine if these mechanisms are similar to those that the group has already identified in ME/CFS. Whatever the outcome, the comparison will be instructive, and will help elucidate the meaning of the genetic ‘signature’ for ME/CFS.

Confirming Your (Gene) Signature

Gene expression is the way in which the information inherited from our parents (usually “recorded” as a gene, a sequence of DNA) is translated into a product, such as a protein or an RNA molecule, that can be used by the body. There are now a number of world-wide research groups investigating gene expression in people with ME/CFS, and over the past few years the number of published scientific reports in this field has been steadily increasing (as shown in the table). Some of these studies have not, unfortunately, confirmed their microarray results with real-time polymerase chain reaction (PCR), a flaw which makes interpretation of the results extremely difficult. However, when PCR-confirmed studies are examined, the genes identified in ME/CFS seem related to ‘‘immunity and defence’’, supporting what is already known about the role of the immune system in the illness.

ME Research UK and the Irish ME Trust have actioned “seed corn” funding for Dr Kerr’s group at St George’s University of London to perform a “confirmatory” study of the putative ME/CFS gene signature in a group of 25 patients who became ill after service in the Gulf War 1990-1991, and who report the standard ME/CFS symptoms of fatigue, joint and muscle pain, cognitive complaints, sleep disturbances, and gastrointestinal problems. After full clinical assessment and characterisation of gene expression and protein analysis, it will be possible to tell if the gene signature is similar (suggesting a common pathogenesis) or different (suggesting an entirely different aetiology) to the illness known as ME/CFS.

Gene expression studies in ME/CFS