[t]Search for the aetiology of ME/CFS. Development of a rational diagnostic system based on microbiological biomarkers[/t]
Investigators
Prof. Jonas Blomberg and colleagues
Prof. Jonas Blomberg
Institution
Clinical Microbiology, Uppsala Academic Hospital, Uppsala University, Uppsala, Sweden
Background and aims
Traditionally, myalgic encephalomyelitis has been associated with “outbreaks” of an epidemic character (see the list here), such as the famous example in 1955 at the Royal Free Hospital, London (page 12 in the Acheson article). Even today, around half of all ME/CFS patients – non-epidemic cases seen in clinics all over the developed world – report that their illness started with an acute, infectious-like episode. So, it’s no surprise there has been some research interest in which infectious agents might be involved, either in causing the illness or in maintaining its severity. The table below lists some of the main viruses or bacteria that have been implicated in ME/CFS at some time, though to date no single agent has been proved to be the “smoking gun” in a majority of cases.
Viruses and bacteria implicated in ME/CFS
Viruses
Enteroviruses, including coxsackievirus
Epstein-Barr virus (EBV)
Cytomegalovirus
Human herpes virus 6
Parvovirus B19
Bacteria
Chlamydia pneumoniae
Coxiella burnetii (Q-fever)
Mycoplasma spp.
Brucella spp
Borrelia burgdorferi (Lyme disease)
Given the potential importance of the role of infection in the illness, the aim of this study by Swedish researchers is to “interrogate” exhaustively a group of ME/CFS patients for evidence of a specific persistent or past infection. The team, headed by Prof. Jonas Blomberg at the University of Uppsala, Sweden, will hunt for nucleic acids from and antibodies (primarily immunoglobulin G) against microbes previously reported to occur in elevated amounts or increased frequency in ME/CFS patients. Importantly, the researchers will use novel multiplex technology which allows one blood sample to be tested for a large number of different infectious agents at the same time. The technique means that multiple pathogens are tested for simultaneously, which diminishes variation between assays and tests, and reduces assay time and costs.
Part of the new project consists of a development phase, involving the refinement of a variation tolerant capture multiplex assay or VOCMA capable of probing for a large number of potentially relevant infectious agents. The major phase, however, involves deploying this multiplex technology to probe for nucleic acids (the identifying signatures of microbes) to around 15 infectious agents previously reported to be connected with ME/CFS. The method is flexible: it can be adapted to include new microbes, and if some microbes do not yield useful information, they can be excluded. The agents investigated will include RNA viruses (such as enteroviruses); small DNA viruses (such as parvovirus); large DNA viruses (such as EBV and herpes virus 6); and bacteria, including Staphylocci, Borrelia, Chlamydiae and Mycoplasma. In addition, sensitive antibody tests will establish whether patients have ever been in contact with infectious agents.
The aim of ME Research UK’s support is to “pump prime” the project, which is part of a larger investigation by the Swedish group on the development of biomarkers in ME/CFS. This is the second grant that we have awarded to Prof. Jonas Blomberg’s team. The first, funded in conjunction with the Irish ME Trust was a thorough investigation of the possible presence of XMRV in Swedish patients. The results of this 18-month project (Elfaitouri et al, PLoS ONE, 2011) were that XMRV and related virus could not be detected by several different methods (virus isolation, PCR and serology) in white blood cells or plasma from Swedish patients with ME/CFS or fibromyalgia, or in blood sera from Swedish blood donors, using the sensitive PCR techniques specifically developed.
Despite these negative findings, which accorded with results from other research groups around the world, Prof. Blomberg was determined to continue the hunt for viruses and bacteria which might be involved in this serious illness. As he says, “"Given the range and scope of intriguing findings by separate research groups, the situation is ripe for creation of a set of biomarkers. Some might be proteins in cerebrospinal fluid or blood, some might be immunological, and some might be microbiological (nucleic acid and antimicrobial antibody) as our investigation using multiplex technology hopes to reveal. Together with good clinical data (including neuroimaging), I think we have a chance of creating a robust set of criteria which can aid in the diagnosis and perhaps also reveal more about the origins of ME/CFS."”
