| 1. |
- Augutis, Kristin, et al.
(författare)
-
Cerebrospinal fluid biomarkers of β-amyloid metabolism in multiple sclerosis.
- 2013
-
Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 19:5, s. 543-52
-
Tidskriftsartikel (refereegranskat)abstract
- Amyloid precursor protein (APP) and amyloid β (Aβ) peptides are intensely studied in neuroscience and their cerebrospinal fluid (CSF) measurements may be used to track the metabolic pathways of APP in vivo. Reduced CSF levels of Aβ and soluble APP (sAPP) fragments are reported in inflammatory diseases, including multiple sclerosis (MS); but in MS, the precise pathway of APP metabolism and whether it can be affected by disease-modifying treatments remains unclear.
|
|
| 2. |
- Axelsson, Markus, 1975, et al.
(författare)
-
Immunosuppressive therapy reduces axonal damage in progressive multiple sclerosis.
- 2014
-
Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - London, United Kingdom : SAGE Publications. - 1477-0970 .- 1352-4585. ; 20:1, s. 43-50
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In progressive multiple sclerosis (PMS), disease-modifying therapies have not been shown to reduce disability progression. OBJECTIVE: The impact from immunosuppressive therapy in PMS was explored by analyzing cerebrospinal fluid (CSF) biomarkers of axonal damage (neurofilament light protein, NFL), astrogliosis (glial fibrillary acidic protein, GFAP), and B-cell regulation (CXCL13). METHODS: CSF was obtained from 35 patients with PMS before and after 12-24 months of mitoxantrone (n=30) or rituximab (n=5) treatment, and from 14 age-matched healthy control subjects. The levels of NFL, GFAP, and CXCL13 were determined by immunoassays. RESULTS: The mean NFL level decreased by 51% (1781 ng/l, SD 2018 vs. 874 ng/l, SD 694, p=0.007), the mean CXCL13 reduction was 55% (9.71 pg/ml, SD 16.08, vs. 4.37 pg/ml, SD 1.94, p=0.008), while GFAP levels remained unaffected. Subgroup analysis showed that the NFL reduction was confined to previously untreated patients (n=20) and patients with Gd-enhancing lesions on magnetic resonance imaging (n=12) prior to study baseline. CONCLUSIONS: Our data imply that 12-24 months of immunosuppressive therapy reduces axonal damage in PMS, particularly in patients with ongoing disease activity. Determination of NFL levels in CSF is a potential surrogate marker for treatment efficacy and as endpoint in phase II trials of MS.
|
|
| 3. |
- Axelsson, Markus, 1975, et al.
(författare)
-
The influence of disease duration, clinical course, and immunosuppressive therapy on the synthesis of intrathecal oligoclonal IgG bands in multiple sclerosis.
- 2013
-
Ingår i: Journal of Neuroimmunology. - : Elsevier BV. - 0165-5728. ; 264:1-2, s. 100-5
-
Tidskriftsartikel (refereegranskat)abstract
- We investigated the impact of disease duration, clinical course and immunosuppressive therapy on intrathecal IgG synthesis in multiple sclerosis (MS). Cerebrospinal fluid (CSF) was obtained twice, 8-10years apart, from 20 MS patients and 26 healthy controls, and from 22 MS patients before and after two years of mitoxantrone treatment. The oligoclonal IgG band patterns changed in 15 patients at long-term follow-up, but were only influenced in 4 patients by mitoxantrone therapy. The CSF B-cell-regulating chemokine CXCL13 correlated with intrathecal IgG production suggesting a B-cell-dependence of intrathecal IgG synthesis in MS.
|
|
| 4. |
- Gunnarsson, Martin, et al.
(författare)
-
Axonal damage in relapsing multiple sclerosis is markedly reduced by natalizumab.
- 2011
-
Ingår i: Annals of neurology. - : Wiley. - 1531-8249 .- 0364-5134. ; 69:1, s. 83-9
-
Tidskriftsartikel (refereegranskat)abstract
- The impact of present disease-modifying treatments (DMTs) in multiple sclerosis (MS) on nerve injury and reactive astrogliosis is still unclear. Therefore, we studied the effect of natalizumab treatment on the release of 2 brain-specific tissue damage markers into cerebrospinal fluid (CSF) in MS patients.
|
|
| 5. |
- Jernås, Margareta, 1961, et al.
(författare)
-
MicroRNA regulate immune pathways in T-cells in multiple sclerosis (MS)
- 2013
-
Ingår i: BMC Immunology. - : Springer Science and Business Media LLC. - 1471-2172. ; 14:32
-
Tidskriftsartikel (refereegranskat)abstract
- Background: MicroRNA are small noncoding RNA molecules that are involved in the control of gene expression. To investigate the role of microRNA in multiple sclerosis (MS), we performed genome-wide expression analyses of mRNA and microRNA in T-cells from MS patients and controls.Methods: Heparin-anticoagulated peripheral blood was collected from MS-patients and healthy controls followed by isolation of T-cells. MicroRNA and RNA from T-cells was prepared and hybridized to Affymetrix miR 2.0 array and Affymetrix U133Plus 2.0 Human Genome array (Santa Clara, CA), respectively. Verifications were performed with real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA).Results: We identified 2,452 differentially expressed genes and 21 differentially expressed microRNA between MS patients and controls. By Kolmogorov-Smirnov test, 20 of 21 differentially expressed microRNA were shown to affect the expression of their target genes, many of which were involved in the immune system. Tumor necrosis factor ligand superfamily member 14 (TNFSF14) was a microRNA target gene significantly decreased in MS. The differential expression of mir-494, mir-197 and the predicted microRNA target gene TNFSF14 was verified by real-time PCR and ELISA.Conclusion: These findings indicate that microRNA may be important regulatory molecules in T-cells in MS.
|
|
| 6. |
- Jernås, Margareta, 1961, et al.
(författare)
-
MS risk genes are transcriptionally regulated in CSF leukocytes at relapse
- 2013
-
Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 19:4, s. 403-410
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Infiltrating T-helper cells, cytotoxic T-cells, B-cells and monocytes are thought to mediate the damage to myelin, oligodendrocytes and axons in multiple sclerosis (MS), which results in progressive disability. OBJECTIVE: The objective of this paper is to explore gene expression profiles of leukocytes in the cerebrospinal fluid (CSF) compartment of MS patients during relapse. METHODS: Global gene expression was analyzed by DNA microarray analysis of cells in CSF from MS patients and controls, and verifications were performed with real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). RESULTS: Fifty percent of the recently described risk genes for MS and 28% of non-risk genes were differently expressed in MS patients compared to controls (χ(2)-test, p=7.7 × 10(-5)). Genes involved in T- and NK-cell processes were up-regulated, and genes involved in processes targeting innate immunity or B-cells were down-regulated in MS. Increased expression of EDN1 and CXCL11 and decreased expression of HMOX1 was verified with real-time PCR and increased expression of CXCL13 was verified with ELISA in CSF. CONCLUSION: DNA microarray analysis is useful in identifying differently expressed genes in CSF leukocytes, which may be important in MS in vivo. Our findings suggest that many of the risk genes for MS are differently expressed in the disease-mediating leukocytes that penetrate the blood-brain barrier.
|
|
| 7. |
- Kuhle, J, et al.
(författare)
-
Neurofilament light and heavy subunits compared as therapeutic biomarkers in multiple sclerosis
- 2013
-
Ingår i: Acta neurologica Scandinavica. - : Hindawi Limited. - 1600-0404 .- 0001-6314. ; 128:6
-
Tidskriftsartikel (refereegranskat)abstract
- Neurofilaments are promising biomarkers in multiple sclerosis (MS) and increased levels in cerebrospinal fluid (CSF) indicate axonal damage or degeneration. In a previous study, neurofilament light chain (NfL) levels in CSF of relapsing remitting (RR) patients with MS were normalized by natalizumab treatment.We compared the coherence between NfL and neurofilament heavy chain (NfH(SMI) (35) ) levels in longitudinal CSF samples in a subset of these patients.In 30 patients with RRMS, CSF was obtained prior to and following 12months of natalizumab treatment. NfH(SMI) (35) was measured by an electrochemiluminescence-based immunoassay. NfL levels were determined previously by the UmanDiagnostics NF-light(®) assay.NfH(SMI) (35) decreased in 73.3% and NfL in 90% of the patients following natalizumab treatment (32.4 vs 27.4pg/ml, P=0.002 and 820 vs 375pg/ml, P<0.0001). Patients experiencing a relapse showed higher NfH(SMI) (35) levels compared with patients in remission (47.7 vs 27.6pg/ml, n=8, P=0.001). This difference was less obvious for NfL (1055 vs 725pg/ml, P=0.256). In patients in remission, NfL levels were lower following natalizumab treatment (830 vs 365pg/ml, n=20, P=0.0002), whereas the same comparison failed significance for NfH(SMI) (35) (28.3 vs 26.9pg/ml, P=0.086).We confirm previous findings, indicating reduced axonal damage under natalizumab treatment by measuring NfH(SMI) (35) , using an assay with independent methodology. In comparison with NfH(SMI) (35) , NfL changes were more pronounced and the treatment effect also included patients in remission. Our results suggest that NfL is superior over NfH(SMI) (35) as therapeutic biomarker and is a promising candidate to measure neuroaxonal damage in MS treatment trials.
|
|
| 8. |
- Malmeström, Clas, 1965, et al.
(författare)
-
CSF levels of YKL-40 are increased in MS and replaces with immunosuppressive treatment.
- 2014
-
Ingår i: Journal of neuroimmunology. - : Elsevier BV. - 1872-8421 .- 0165-5728. ; 269:1-2, s. 87-9
-
Tidskriftsartikel (refereegranskat)abstract
- The role of glial cells during different phases of multiple sclerosis (MS) is unclear. To monitor glial activation we analyzed the biomarkers YKL-40 and sCD14 in cerebrospinal fluid (CSF) from MS patients during different disease phases and in response to immunosuppressive treatment. CSF levels of YKL-40 were increased in MS during relapse, remission and secondary progression compared with healthy controls. Furthermore, YKL-40 levels in CSF decreased by mitoxantrone and natalizumab treatment. No differences were observed in CSF levels of sCD14. Thus, we can infer that glial activation is present in all MS phases and decreases by immunosuppressive treatment.
|
|
| 9. |
- Malmeström, Clas, 1965, et al.
(författare)
-
Serum levels of LIGHT in MS
- 2013
-
Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 19:7, s. 871-876
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Recently, a polymorphism in the LIGHT gene was shown to increase the risk of multiple sclerosis (MS) in a genome-wide association study (GWAS). OBJECTIVE: Our aim was to investigate if serum levels of LIGHT were affected by this polymorphism and by the disease itself. METHODS: Serum levels of LIGHT were investigated in four cohorts; 1) MS (n = 159) and controls (n = 160) in relation to rs1077667 genotype; 2) MS at relapse (n = 30) vs. healthy controls (n = 26); 3) MS (n = 27) vs. other neurological disease (OND, n = 33); and 4) MS patients before and after one year of treatment with natalizumab (n = 30). RESULTS: Carriers of the GG genotype had the lowest serum levels of LIGHT (p=0.02). Serum levels of LIGHT were increased in MS at relapse in two separate cohorts: vs. healthy controls (p=0.00005) and vs. remission (p=0.00006), other neurological disease (OND) (p=0.002) and OND with signs of inflammation (iOND; p=0.00005). Furthermore, serum levels of LIGHT were decreased by natalizumab treatment (p=0.001). CONCLUSION: Soluble LIGHT is an inhibitor of T-cell activation and GG carriers of rs1077667, with the highest risk for MS, had the lowest serum levels. The increased levels of LIGHT at times of increased MS activity suggest that soluble LIGHT is protective and may act to limit inflammation.
|
|
