Prediction of acute multiple sclerosis relapses by transcription levels of peripheral blood cells.
BACKGROUND
The ability to predict the spatial frequency of relapses in multiple sclerosis (MS) would enable physicians to decide when to intervene more aggressively and to plan clinical trials more accurately.


METHODS
In the current study our objective was to determine if subsets of genes can predict the time to the next acute relapse in patients with MS. Data-mining and predictive modeling tools were utilized to analyze a gene-expression dataset of 94 non-treated patients; 62 patients with definite MS and 32 patients with clinically isolated syndrome (CIS). The dataset included the expression levels of 10,594 genes and annotated sequences corresponding to 22,215 gene-transcripts that appear in the microarray.


RESULTS
We designed a two stage predictor. The first stage predictor was based on the expression level of 10 genes, and predicted the time to next relapse with a resolution of 500 days (error rate 0.079, p < 0.001). If the predicted relapse was to occur in less than 500 days, a second stage predictor based on an additional different set of 9 genes was used to give a more accurate estimation of the time till the next relapse (in resolution of 50 days). The error rate of the second stage predictor was 2.3 fold lower than the error rate of random predictions (error rate = 0.35, p < 0.001). The predictors were further evaluated and found effective both for untreated MS patients and for MS patients that subsequently received immunomodulatory treatments after the initial testing (the error rate of the first level predictor was < 0.18 with p < 0.001 for all the patient groups).


CONCLUSIONS
We conclude that gene expression analysis is a valuable tool that can be used in clinical practice to predict future MS disease activity. Similar approach can be also useful for dealing with other autoimmune diseases that characterized by relapsing-remitting nature.
Gurevich
Michael
M
Multiple Sclerosis Center, Sheba Medical Center, Tel-Hashomer, Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel. Michael.Gurevich@sheba.health.gov.il
Tuller
Tamir
T
Rubinstein
Udi
U
Or-Bach
Rotem
R
Achiron
Anat
A