This study looks at neuroinflammation. Specifically the fact that the development of treatments for progressive MS is hampered by the lack of suitable biomarkers that can accurately detect and monitor intrathecal inflammation (inflammation which occurs within the spinal theca, which is a sac containing the cerebrospinal fluid which provides nutrients and buoyancy to the spinal cord).
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Romme Christensen J, Komori M, von Essen MR, Ratzer R, Börnsen L, Bielekova B, Sellebjerg F. CSF inflammatory biomarkers responsive to treatment in progressive multiple sclerosis capture residual inflammation associated with axonal damage. Mult Scler. 2018 May 1:1352458518774880. doi: 10.1177/1352458518774880. [Epub ahead of print]
BACKGROUND: Development of treatments for progressive multiple sclerosis (MS) is challenged by the lack of sensitive and treatment-responsive biomarkers of intrathecal inflammation.
OBJECTIVE: To validate the responsiveness of cerebrospinal fluid (CSF) inflammatory biomarkers to treatment with natalizumab and methylprednisolone in progressive MS and to examine the relationship between CSF inflammatory and tissue damage biomarkers.
METHODS: CSF samples from two open-label phase II trials of natalizumab and methylprednisolone in primary and secondary progressive MS. CSF concentrations of 20 inflammatory biomarkers and CSF biomarkers of axonal damage (neurofilament light chain (NFL)) and demyelination were analysed using electrochemiluminescent assay and enzyme-linked immunosorbent assay (ELISA).
RESULTS: In all, 17 natalizumab- and 23 methylprednisolone-treated patients had paired CSF samples. CSF sCD27 displayed superior standardised response means and highly significant decreases during both natalizumab and methylprednisolone treatment; however, post-treatment levels remained above healthy donor reference levels. Correlation analyses of CSF inflammatory biomarkers and NFL before, during and after treatment demonstrated that CSF sCD27 consistently correlates with NFL.
CONCLUSION: These findings validate CSF sCD27 as a responsive and sensitive biomarker of intrathecal inflammation in progressive MS, capturing residual inflammation after treatment. Importantly, CSF sCD27 correlates with NFL, consistent with residual inflammation after anti-inflammatory treatment being associated with axonal damage.
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My comments
CD27 is required for the generation and long-term maintenance of T cell immunity. It binds to ligand CD70, and plays a key role in regulating B-cell activation and immunoglobulin synthesis and may play an important role in the apoptosis (cell suicide) of white blood cells. It is a marker of memory T and B cells. It can be shed to float in the blood in solution, and can be detected. When you have immune activity the CD27 marker is shed.
In this study it shows that CD27 (a marker of immune activation) and neurofilament (a marker of nerve damage) can still be found in some people, even AFTER they have been treated with immunomodulatory drugs (drugs that modify the immune system). So there is still disease activity.
Neurologists have been using neurofilament markers in the decision making process when deciding the best treatments for patients. But not CD27.
There was a correlation between immune activity and nerve damage. Whilst these were reduced by therapy, disease was not always kept in check. So NEDA (no evidence of disease activity) is only as good as what you look for.
Other studies point towards soluble CD27 as being a useful marker of disease activity.
Another study
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Wong YYM, van der Vuurst de Vries RM, van Pelt ED, Ketelslegers IA, Melief MJ, Wierenga AF, Catsman-Berrevoets CE, Neuteboom RF, Hintzen RQ; Dutch paediatric MS and ADEM study group. T-cell activation marker sCD27 is associated with clinically definite multiple sclerosis in childhood-acquired demyelinating syndromes. Mult Scler. 2018 Jul 1:1352458518786655. doi: 10.1177/1352458518786655. [Epub ahead of print]
BACKGROUND:
Cerebrospinal fluid (CSF) levels of T-cell activation marker soluble CD27 (sCD27) are associated with subsequent disease activity after a first attack of suspected MS in adults. The predictive value for disease course in children with acquired demyelinating syndromes (ADS) is unknown.
OBJECTIVES:To assess the predictive value of sCD27 levels for clinically definite multiple sclerosis (CDMS) diagnosis in childhood ADS.
METHODS:Children <18 years with a first demyelinating event were prospectively included and followed. Soluble CD27 was determined in CSF using an enzyme-linked immunosorbent assay (ELISA). Cox regression analyses were used to calculate hazard ratios (HRs) for CDMS.
RESULTS: A total of 94 ADS children were included (ADS with encephalopathy (ADS+) n = 33 and ADS without encephalopathy (ADS-) n = 61). Of the 61 ADS- children, 21 (48%) were diagnosed with CDMS during follow-up. At baseline, sCD27 levels were higher in patients with a future CDMS diagnosis ( n = 29) than in monophasic ADS+ ( n = 30), monophasic ADS- ( n = 28) and relapsing non-MS patients ( n = 7; p < 0.001). In ADS- patients, sCD27 was associated with CDMS (HR = 1.8 per 100 U/mL increase in sCD27 levels, p = 0.031), after adjustments for age, oligoclonal bands and the presence of dissemination in space on baseline magnetic resonance imaging (MRI).
CONCLUSION: CSF sCD27 levels at first attack of demyelination were associated with CDMS diagnosis in children. This makes sCD27 a potential clinically relevant quantitative marker when performing routine CSF diagnostics.
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(CD27 is a marker of activated T and B cells)
Labels: Biomarker