inflammation in progressive multiple sclerosis involves follicular
T-helper, Th17- and activated B-cells and correlates with progression. PLoS One. 2013; 8(3): e57820. doi: 10.1371/journal.pone.0057820.
studies of progressive multiple sclerosis (MS) indicate a major role of
inflammation including Th17-cells and meningeal inflammation with
ectopic lymphoid follicles, B-cells and plasma cells, the latter
indicating a possible role of the newly identified subset of follicular
T-helper (T) cells. Although previous studies reported increased
systemic inflammation in progressive MS it remains unclear whether
systemic inflammation contributes to disease progression and intrathecal
Aims & methods: This study aimed to investigate systemic inflammation in
progressive MS and its relationship with disease progression, using flow
cytometry and gene expression analysis of CD4 and CD8T-cells, B-cells,
monocytes and dendritic cells. Furthermore, gene expression of
cerebrospinal fluid cells was studied.
Results: Flow cytometry studies revealed
increased frequencies of ICOST-cells in peripheral blood from
relapsing-remitting (RRMS) and secondary progressive (SPMS) MS patients.
All MS subtypes had decreased frequencies of Th1 T-cells, while primary
progressive (PPMS) MS patients had increased frequency of Th17 T-cells.
The Th17-subset, interleukin-23-receptor CD4T-cells, was significantly
increased in PPMS and SPMS. In the analysis of B-cells, we found a
significant increase of plasmablasts and DC-SIGN and CD83B-cells in
SPMS. ICOST-cells and DC-SIGNB-cells correlated with disease progression
in SPMS patients. Gene expression analysis of peripheral blood cell
subsets substantiated the flow cytometry findings by demonstrating
increased expression of , and in CD4 T-cells in progressive MS.
Cerebrospinal fluid cells from RRMS and progressive MS (pooled SPMS and
PPMS patients) had increased expression of T-cell and plasmablast
Conclusions: In conclusion, this study is the first to demonstrate the
potential involvement of activated T-cells in MS. The increased
frequencies of Th17-cells, activated T- and B-cells parallel findings
from pathology studies which, along with the correlation between
activated T- and B-cells and disease progression, suggest a pathogenic
role of systemic inflammation in progressive MS. These observations may
have implications for the treatment of progressive MS.
What causes progressive MS is still not clear. The failure of T cell therapy to have a major influence on progressive MS, has questioned the role of this part of the immune system in progression. However many people think that the problem with MS is all simply a problem of the immune system. This study looks at the blood of relapsing and progressive MSers. They find an increased occurrance of Th17 cells in primary and secondary progressive MS. Is this causal or an epiphenomenon? The best way to find out is get rid of them and see if it impacts progressive MS. Many cells in the blood will be passengers for the day, whether they are reflective of the disease causing cells requires further study.