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Irina Elovaara

Publications and source records attributed to Irina Elovaara.

9 recordsLinked to original sources
PubMed2006

Elevated serum soluble vascular adhesion protein-1 (VAP-1) in patients with active relapsing remitting multiple sclerosis.

Vascular adhesion protein-1 (VAP-1) is an endothelial cell molecule which controls leukocyte infiltration into tissues. Elevated serum soluble VAP-1-levels have been described in certain diseases with an inflammatory component. VAP-1 expression or function has not previously been studied in multiple sclerosis (MS). We report here that the concentration of soluble VAP-1 in serum is significantly higher in multiple sclerosis patients with ongoing inflammatory activity, as demonstrated by gadolinium-enhancing MRI lesions, when compared to patients with no gadolinium-enhancing lesions (555+/-195 vs. 388+/-102 ng/ml, p=0.0068). We propose that VAP-1 might participate in controlling leukocyte entry into inflamed brain.

Adult↗
PubMed2006

Gene expression profiles in Finnish twins with multiple sclerosis.

BACKGROUND: Since genetic alterations influencing susceptibility to multiple sclerosis (MS), the most common autoimmune demyelinating disease of the central nervous system (CNS), are as yet poorly understood, the purpose of this study was to identify genes responsible for MS by studying monozygotic (MZ) twin pairs discordant for MS. METHODS: In order to identify genes involved in MS development, the gene expression profiles in blood mononuclear cells obtained from eight MZ twin pairs discordant for MS were analyzed by cDNA microarray technology detecting the expression of 8 300 genes. The twins were collected from the Finnish Twin Cohort Study and both affected subjects and their healthy siblings underwent neurological evaluation and cerebral and spinal magnetic resonance imaging. Gene expressions were confirmed by relative quantitative reverse transcription PCR. RESULTS: It appeared that 25 genes were at least two-fold up-regulated and 15 genes down-regulated in 25% (2/8) of twins with MS when compared to their healthy siblings. Moreover, 6/25 genes were up-regulated in 40% of MS twins and one gene, interferon alpha-inducible protein (clone IFI-6-16) (G1P3), in 50% of them. The six most constantly expressed genes are (1) G1P3, (2) POU domain, class 3, transcription factor 1, (3) myxovirus resistance 2, (4) lysosomal-associated multispanning membrane protein-5, (5) hemoglobin alpha 2 and (6) hemoglobin beta. CONCLUSION: Over two-fold up-regulation of these six genes in almost half of MZ twins with MS suggests their role in MS pathogenesis. Studies using MZ MS twins obtained from genetically homogeneous population offer a unique opportunity to explore the genetic nature of MS.

Diseases in Twins↗
PubMed2006

[Not Available].

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Journal Article↗
PubMed2006

[Not Available].

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Journal Article↗
PubMed2005

Fine mapping of the multiple sclerosis susceptibility locus on 5p14-p12.

Linkage analyses have identified four major MS susceptibility loci in Finns. Here we have fine mapped the region on chromosome 5p in 28 Finnish MS families. Marker D5S416 provided the highest pairwise LOD score, and multipoint and haplotype analyses restrict the critical region to about 5.3 Mb on 5p15 between markers D5S1987 and D5S416. Ascertaining for HLA type and geographical origin indicated that families with and without the HLA DR15 risk haplotype, as well as families within and outside an internal high-risk region, contributed to the linkage to 5p, implying the general significance for this locus in Finnish MS families.

Chromosome Mapping↗
PubMed2004

Suppression of immune system genes by methylprednisolone in exacerbations of multiple sclerosis. Preliminary results.

Acute relapses of multiple sclerosis (MS) are treated with intravenous methylprednisolone (IVMP), which speeds recovery from exacerbation. It is known that IVMP suppresses the immunological activation which occurs during an acute attack of MS. However, the specific target genes affected by this therapy remain obscure. A cDNA microarray for 448 genes was used to identify the target genes in IVMP therapy. Total RNA was isolated from peripheral blood mononuclear cells derived from six MS patients immediately before and after completion of therapy. IVMP significantly reduced mRNA levels for T-cell-specific transcription factor 7 (p=0.02), T-cell-specific protein-tyrosine kinase (p=0.02), T-cell surface glycoprotein CD5 (p=0.05) and interferon-stimulated gene factor 3 gamma subunit (p=0.04). Significantly increased expression was found for eosinophil-derived neurotoxin (p=0.05). The suppression of expression of genes associated with T-cell differentiation and antigen-specific T-cell activation detected in this study may contribute to the beneficial effect of MP in relapses of MS.

Adult↗
PubMed2002

Fine mapping of a multiple sclerosis locus to 2.5 Mb on chromosome 17q22-q24.

Genome-wide linkage analyses performed in a Finnish study sample have identified four potential predisposing loci for multiple sclerosis (MS). Here we made an effort to restrict the wide linkage region on chromosome 17 with a dense set of 31 markers using multipoint linkage analyses and monitoring for shared marker alleles in MS chromosomes. We carried out the linkage analyses in 22 Finnish multiplex MS families originating from a regional subisolate that shows an exceptionally high prevalence of MS in order to minimize the genetic and environmental heterogeneity of the study sample. Thirty markers on the 23 cM initial interval gave positive pairwise LOD scores. We monitored for shared haplotypes among affected family members within a family, and identified an approximately 4 cM region flanked by the markers D17S1792 and ATA43A10 in 17 out of the 22 families (77.3%). The multipoint linkage analyses using Genehunter and SIMWALK 2.40 provided further evidence for the same 4 cM region, for example a maximal multipoint NPL score of 5.98 (P<0.0002). We observed nominal evidence for association to MS, with one marker flanking the shared region, and this association was replicated in the additional set of families. Using the combined power of linkage, association and shared haplotype analyses, we were thus able to restrict the MS locus on chromosome 17q from 23 cM to a 4 cM region covering a physical interval of approximately 2.5 Mb. Thus, this study describes the restriction of an MS locus outside the HLA region into a segment approachable by molecular tools.

Chromosomes, Human, Pair 17↗
PubMed2002

Differential intracellular expression of CCR5 and chemokines in multiple sclerosis subtypes.

Chemokines are small chemoattractant cytokines which participate in the migration of immune cells into the CNS and contribute to the T cell-mediated pathogenesis of multiple sclerosis (MS). The expression of chemokines and their receptors in freshly isolated mononuclear cells from peripheral blood (PBMC) was studied in relation to MS subtype, disease duration and progression in a total of 57 patients with MS (22 relapsing remitting, RRMS; 21 secondary progressive, SPMS; 14 primary progressive, PPMS) and 17 healthy controls. The RNA expression of CCR5 in PBMC was analysed by reverse transcription polymerase chain reaction (RT-PCR) using specific oligonucleotide primers. The PBMC levels of CCR5-ligands MIP-1 alpha/beta and RANTES, and chemokines MCP-1, IL-8, lymphotactin, IP-10 and I-309 were analysed by ribonuclease protection assay (RPA). Significantly increased intracellular CCR5 RNA expression intensity was detected in PPMS when compared with SPMS ( p=0.009), RRMS ( p=0.013), and controls ( p=0.023). However, the surface expression of CCR5 on CD4(+) cells from PBMC, analysed by flow cytometry, appeared to be similar in all MS subtypes and controls. The CCR5-ligands RANTES and MIP-1b were expressed constitutively in all patients and controls. Interleukin-8 was found in all MS subtypes and controls, but IP-10 was detected only in RRMS and SPMS, and lymphotactin occasionally in other subtypes but PPMS. MCP-1, MIP-1a or I-309 were not expressed in any of the groups studied. A correlation was found between the RNA levels of RANTES and CCR5 in PPMS ( r=0.735). Differential profile in the expression of CCR5 and chemokines between PPMS and other MS subtypes may contribute to differences in the pathogenesis of MS and thus can be of importance in the development of new treatments for MS.

Adult↗