Despite considerable advances in the treatment of multiple sclerosis, current drugs are only partially effective. Most patients show reduced disease activity with therapy, but still experience relapses, increasing disability, and new brain lesions. Since there are no reliable clinical or biological markers of disease progression, long-term outcome is difficult to predict for individual patients.
We identified 18 studies that suggested genes expressed in blood as predictive biomarkers. We validated the prognostic value of those genes with three different microarray data sets comprising 148 patients in total. Using these data, we tested whether the genes were significantly differentially expressed between patients with good and poor courses of the disease. Poor progression was defined by relapses and/or increase of disability during a two-year follow-up, independent of the administered therapy.
RESULTS: Of 110 genes that have been proposed as predictive biomarkers, most could not be confirmed in our analysis. However, the G protein-coupled membrane receptor GPR3 was expressed at significantly lower levels in patients with poor disease progression in all data sets. GPR3 has therefore a high potential to be a biomarker for predicting future disease activity.
In addition, we examined the IL17 cytokines and receptors in more detail and propose IL17RC as a new, promising, transcript-based biomarker candidate. Further studies are needed to better understand the roles of these receptors in multiple sclerosis and its treatment and to clarify the utility of GPR3 and IL17RC expression levels in the blood as markers of long-term prognosis.
Levels of GPR3 and IL-17RC in MSers. Some had a favourable disease course compared to others
As is often the case much research can not be reproduced and most biomarkers (indicators of a biological function) previously reported have not been reproduced in this study, whilst this is perhaps wasteful, through repetition a consensus is achieved and progress is then moved forward.
However, I am not yet convinced that GPR3 or IL17RC are going to prove useful of a biomarker either, because there is too much overlap between the levels found in people with a good outcome compared to those with a bad outcome (see above). So the search will continue