Biomedical Research Searching for Microbiological Biomarkers
Traditionally, Myalgic Encephalomyelitis has been associated with outbreaks of an epidemic character, such as the famous example in 1955 at the Royal Free Hospital, London. Even today, around half of all ME/CFS patients – non-epidemic cases seen in clinics throughout the developed world – report that their illness started with an acute, infectious-like episode. So, it’s no surprise there has been some research into which infectious agents might be involved, either in causing the illness or in maintaining its severity.
Several viruses or bacteria 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. It is most likely that various different infectious agents can trigger the disease, and that the characteristics and development of the subsequent illness will depend on the genetic make-up and immune competence of the person infected. Also, the type of infection might be an important factor; as the scientific review by Devanur and Kerr (Journal of Clinical Virology, 2006) pointed out, viruses can trigger ME/CFS either by a hit-and-run mechanism (in which the virus is present at the beginning of the illness but cannot be detected later) or through a persistent infection (in which the virus is present both at the beginning of the illness and after months or years, and is detectable in patients with ME/CFS presenting to the clinic).
Given the potential importance of the role of infection in the illness, ME Research UK has awarded a grant to Swedish researchers to interrogate a group of ME/CFS patients exhaustively for evidence of a specific persistent or past infection. The team, headed by Professor Jonas Blomberg at the University of Uppsala, Sweden, will hunt for nucleic acids from microbes reported to occur in elevated amounts or increased frequency in ME/CFS patients. They will also look for antibodies against these same microbes.
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.
This is the second grant that ME Research UK has awarded to Professor 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, Professor Blomberg is determined to continue the hunt for viruses and bacteria which might be involved in this serious illness.
Part of the new project consists of a development phase, involving the refinement of a ‘variation tolerant capture multiplex assay’ (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 fifteen 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 Staphylococci, 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 was to ‘pump-prime’ the project, which is part of a larger investigation by the Swedish group on the development of biomarkers in ME/CFS. No clear consensus on a laboratory diagnostic set of markers has yet emerged in the illness. However, as Professor Blomberg says, “Given the range and scope of intriguing findings by separate research groups, the situation is ripe for the 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 diagnosis and perhaps also reveal more about the origins of ME/CFS.”
This article has been extracted and edited from ME Research UK’s Autumn 2012 issue of Breakthrough magazine. Read it online at the ME Research UK's website or contact ME Research UK, The Gateway, North Methven Street, Perth PH1 5PP. Tel: 01738 451234. Email: firstname.lastname@example.org.