| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Hu, D., et al.
(författare)
-
Transcriptional signature of human pro-inflammatory T(H)17 cells identifies reduced IL10 gene expression in multiple sclerosis
- 2017
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8:1
-
Tidskriftsartikel (refereegranskat)abstract
- We have previously reported the molecular signature of murine pathogenic T(H)17 cells that induce experimental autoimmune encephalomyelitis (EAE) in animals. Here we show that human peripheral blood IFN-gamma(+) IL-17(+) (T(H)1/17) and IFN-gamma(-)-IL-17(+) (T(H)17) CD4(+) T cells display distinct transcriptional profiles in high-throughput transcription analyses. Compared to T(H)17 cells, T(H)1/17 cells have gene signatures with marked similarity to mouse pathogenic T(H)17 cells. Assessing 15 representative signature genes in patients with multiple sclerosis, we find that T(H)1/17 cells have elevated expression of CXCR3 and reduced expression of IFNG, CCL3, CLL4, GZMB, and IL10 compared to healthy controls. Moreover, higher expression of IL10 in T(H)17 cells is found in clinically stable vs. active patients. Our results define the molecular signature of human pro-inflammatory T(H)17 cells, which can be used to both identify pathogenic T(H)17 cells and to measure the effect of treatment on T(H)17 cells in human autoimmune diseases.
|
|
| 5. |
|
|
| 6. |
- Kivisakk, P, et al.
(författare)
-
IL-15 mRNA expression is up-regulated in blood and cerebrospinal fluid mononuclear cells in multiple sclerosis (MS)
- 1998
-
Ingår i: Clinical and experimental immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 111:1, s. 193-197
-
Tidskriftsartikel (refereegranskat)abstract
- IL-15, produced by monocytes and epithelial cells, is a novel cytokine with actions similar to IL-2. IL-15 induces T cell proliferation, B cell maturation and natural killer (NK) cell cytotoxicity, and is a chemoattractant for T cells. We investigated the expression of IL-15 mRNA in blood and cerebrospinal fluid (CSF) mononuclear cells (MNC) in MS, an inflammatory disease of the central nervous system where cytokines are involved. MS patients had higher numbers of IL-15 mRNA-expressing blood MNC than patients with aseptic meningo-encephalitis (AM) and healthy controls. In CSF, MS patients had even higher numbers of IL-15 mRNA-expressing cells than in blood. This discrepancy between IL-15 mRNA expression between blood and CSF MNC was not seen in AM patients. Patients examined during the secondary chronic-progressive phase of MS had higher numbers of IL-15 mRNA-expressing blood MNC compared with patients examined during the relapsing-remitting phase. Levels of IL-15 mRNA-positive blood MNC were similar in patients with AM, myasthenia gravis, non-inflammatory neurological diseases and healthy controls. Taken together these data indicate that IL-15 mRNA expression is up-regulated in MS, further suggesting a role for proinflammatory cytokines in the pathogenesis of MS.
|
|
| 7. |
|
|
| 8. |
- Kivisakk, P, et al.
(författare)
-
Neutralising and binding anti-interferon-beta-I b (IFN-beta-I b) antibodies during IFN-beta-I b treatment of multiple sclerosis
- 1997
-
Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 3:3, s. 184-190
-
Tidskriftsartikel (refereegranskat)abstract
- Interferon-β-1b (IFN-β-1b) is an immunomodulatory therapy of multiple sclerosis (MS), reducing the numbers and severity of exacerbations and the total lesion load measured by magnetic resonance imaging of the brain. The benefits of IFN-β-1b could be hampered by the development of neutralising antibodies against the compound. Our results confirmed earlier studies, showing that 42% of MS patients treated with IFN-β-1b for more than 3 months had developed neutralising antibodies. The occurrence of binding anti-IFN-β-1b antibodies, presently not believed to impede the clinical efficacy of IFN-β-1b, were demonstrated by an immunoassay in some patients already after I month of treatment and in 78% after 3 months. The development of binding antibodies seemed to be an early phenomenon, preceding the appearance of neutralising antibodies. Antibodies crossreacting with IFN-β-1a and natural IFN-β were also found in a majority of IFN-β-1b treated patients with high titres of binding antibodies. Employing a solid-phase enzyme-linked immunospot (ELISPOT) assay, 68% of MS patients treated with IFN-β-1b for 1 -23 months had elevated numbers of anti-IFN-β-1b-antibody secreting cells in blood, compared to 18% of untreated MS patients and 20% among patients with other neurological diseases. Thus, our findings confirm that IFN-β-1 b is immunogenic in MS patients. High levels of anti-IFN-β-1b antibody secreting cells were, however, also found in two untreated control patients with inflammatory diseases, suggesting that anti-IFN-β-1b antibodies might also occur spontaneously.
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
- Kivisakk, P, et al.
(författare)
-
Optic neuritis and cytokines: no relation to MRI abnormalities and oligoclonal bands
- 1998
-
Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 50:1, s. 217-223
-
Tidskriftsartikel (refereegranskat)abstract
- Acute unilateral monosymptomatic optic neuritis (ON) is a common first manifestation of MS if associated with multiple MS-like lesions on brain MRI and oligoclonal IgG bands (OB) in the CSF, whereas ON patients lacking these laboratory abnormalities are considered to have a good prognosis regarding future MS development. Several cytokines involved in immune regulation are upregulated in blood and even more noticeable in CSF in MS. To study a possible relation between cytokine profiles and presence versus absence of MS-like brain MRI lesions and CSF OB, we used in situ hybridization to examine mRNA expression of the proinflammatory interleukin-12 (IL-12), interferon-γ, and tumor necrosis factor-α and the immune response downregulating IL-10, transforming growth factor-β and IL-4 in blood and CSF mononuclear cells (MNC) from 59 patients with untreated ON. There were no differences in numbers of MNC in blood or CSF expressing any of the cytokines under study, upon subgrouping the ON patients regarding presence (n = 31) versus absence (n = 28) of MRI lesions, presence (n = 45) versus absence (n=14) of OB, or duration after onset of ON (<1 month, n = 30, versus >1 month, n = 29). Similarly, no differences were observed for numbers of myelin basic protein-reactive blood MNC expressing any of these cytokines after subrouping according to these variables. Our findings suggest that the cytokine profile, as examined in this study, is less useful to determine the risk of future development of clinically definite MS in ON patients or as indicator for therapeutic interventions in ON. An upregulation of both pro- and anti-inflammatory cytokines in ON patients seems to be more related to the CNS disease per se, whether limited to the optic nerve or not, than to the inflammatory process characteristic for MS.
|
|
| 13. |
|
|
| 14. |
|
|
| 15. |
|
|
| 16. |
|
|
| 17. |
- Matusevicius, D, et al.
(författare)
-
Interleukin-17 mRNA expression in blood and CSF mononuclear cells is augmented in multiple sclerosis
- 1999
-
Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 5:2, s. 101-104
-
Tidskriftsartikel (refereegranskat)abstract
- Myelin-directed autoimmunity is considered to play a key role in the pathogenesis of multiple sclerosis (MS). Increased production of both pro- and anti-inflammatory cytokines is a common finding in MS. Interleukin-17 (IL-17) is a recently described cytokine produced in humans almost exclusively by activated memory T cells, which can induce the production of proinflammatory cytokines and chemokines from parenchymal cells and macrophages. In situ hybridisation with synthetic oligonucleotide probes was adopted to detect and enumerate IL-17 mRNA expressing mononuclear cells (MNC) in blood and cerebrospinal fluid (CSF) from patients with MS and control individuals. Numbers of IL-17 mRNA expressing blood MNC were higher in patients with MS and acute aseptic meningoencephalitis (AM) compared to healthy individuals. Higher numbers of IL-17 mRNA expressing blood MNC were detected in MS patients examined during clinical exacerbation compared to remission. Patients with MS had higher numbers of IL-17 mRNA expressing MNC in CSF compared to blood. This increase in numbers of IL-17 mRNA expressing MNC in CSF was not observed in patients with AM. Our results thus demonstrate increased numbers of IL-17 mRNA expressing MNC in MS with higher numbers in CSF than blood, and with the highest numbers in blood during clinical exacerbations.
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
|
|
| 21. |
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
|
|
| 25. |
|
|
| 26. |
|
|
| 27. |
|
|
