ME Research UK article, 11 Feb 2016: Orosomucoid and ME/CFS
Most scientific reports either confirm what we already know or reveal mildly interesting findings that contribute to the field in a small way. Every now and then, however, a research paper arrives that makes you stop and think (at least for a few minutes), and the most recent comes from researchers at the Second Military Medical University, Shanghai.
The Chinese researchers had been using an animal model to investigate ‘fatigue’ and how the body responds to and regulates it. Their investigations showed that fatigue was accompanied by a rise in orosomucoid (ORM, or alpha-1-acid glycoprotein), with significant increases in a plethora of tissues, including blood and muscle (read more). This was interesting but not surprising as ORM is one of the major ‘acute-phase proteins’ which increase or decrease in blood plasma when inflammation is present. ORM itself is produced by many tissues, though mainly by the liver, and its manufacture is influenced by many factors, such as tissue injury, infection, tobacco smoke, or the presence of other proteins produced by cells. Oddly enough, its precise biological function remains poorly understood, but it is known to be involved in immunity and in the metabolism of various drugs (see a review). The clear relationship between ORM and fatigue in their experimental model led the researchers to wonder whether the protein might, in fact, be raised in people with ME/CFS – with results that (one suspects) surprised even themselves.
Compared with a healthy control group, ORM levels were dramatically elevated in blood serum in Fukuda-defined CFS patients (Figure below).
Indeed, ORM levels were <1 mg/mL in all the healthy controls, but >1 mg/mL in all except one of the ME/CFS patients. ORM expression was not related to serum cortisol level as might have been expected (see a review); hypocortisolism was present in the ME/CFS patients, as expected, but to a mild degree.
[Figure: Blood serum ORM level (mg/mL)]
This result is reported in short letter format, and aims only to bring this unusual phenomenological finding to a wider audience. No published evidence exists to support an association between raised ORM and ME/CFS, apart from the presence of ORM2 (one of the two isoforms of ORM) in a set of 5 proteins found to be increased the cerebrospinal fluid of ME/CFS patients in a study in 2005 (read more). So, a cloud of unknowing hangs over the meaning and validity of this single observation.
There is evidence that levels of ORM (and other acute phase proteins) are raised by infection and inflammation, and that concentrations of ORM in the blood are increased in smokers compared with past or never smokers (read more), though not to the extent seen in the ME/CFS patients in this study. Also, raised levels of ORM, in combination with other markers, have been associated with all-cause mortality in elderly people (read more), as well as some pathological conditions (read more). Interestingly, another member of the acute phase protein family, C-reactive protein, is also raised in ME/CFS patients, as ME Research UK-funded work has shown (read more), with potential consequences for cardiovascular health.
Of course, as Aristotle said, “a single swallow does not a summer make, nor one fine day”, and we are a long way from knowing whether or not ORM will become a valid ‘biomarker’ for a diagnosis of ME/CFS. Any number of confounding factors can throw up an isolated unexpected result, as the XMRV story illustrated some years ago. The next step is for the group in Shanghai to confirm and extend its findings (hopefully with funding from the National Natural Science Foundation of China which kindly funded their previous investigations), and for researchers elsewhere to test for ORM and related acute phase proteins in the blood of their ME/CFS patients. We’ll watch the space with interest.