Multiple sclerosis (MS) is characterized in most patients by a
relapsing-remitting disease course. However, the trigger of relapse and
the transformation that switches relapse into remission are not clearly
understood. To evaluate the key molecular pathways operating in MS
relapse and remission we performed peripheral blood gene-expression
profiling in 123 MS patients either in relapse (n=34) or remission
(n=89) and in comparison with 41 matched healthy subjects using
Affymetrix microarray technology. Our findings suggest that the
relapsing-remitting pattern of MS is an ongoing process where
inflammation is persistently active in the background of a changing
magnitude of processes associated with TBX21-mediated immune suppression
and activation of BDNF-related neuroprotection.
Does the blood really reflect what is occuring in the CNS? I think the answer is whilst there is a hint of activity in the blood it is like a needle in a haystack.
In this study they looked in the blood from people during relapse and from people during remission and in the blood of healthy people. The genes that are active in MSers are immune genes irrespective of whether the disease is active or not but some gene products go up and others go down during relapse. These include T-box transcription factor (TBX21) and brain derived neurotrophic factor which is a nerve survival factor. Studies in mouse show that Tbx21 protein is a Th1 cell-specific transcription factor that controls the expression of the hallmark Th1 cytokine, interferon-gamma (IFNG). Expression of the human ortholog also correlates with interferon gamma, a pro-inflammatory cytokine, expression in Th1 and natural killer cells, suggesting a role for this gene in initiating Th1 lineage development from naive Th precursor cells.
This study suggests that the default situation is inflammatory response and this is either high or low rather than on and off. However one potential problem is that lesions come and go and there are many more lesions than relapses, so the disease is not sleeping when people are in remission. This would have best been done with imaging of the brain and spinal cord to see if disease was silent during remission.
Labels: Relapse recovery