Hanna Kuusisto

Elevated cerebrospinal fluid adiponectin and adipsin levels in patients with multiple sclerosis: a Finnish co-twin study

Background and purpose:  The aim of this study was to investigate the levels of three adipocytokines: leptin, adiponectin and adipsin, in serum and cerebrospinal fluid (CSF) of twins discordant for multiple sclerosis (MS). Adipose tissue is an important component connecting immune system and several tissues and organs including CNS. Fat cells produce adipocytokines, which seem to have a role in various autoimmune disorders including MS.

Apoptosis-related molecules in blood in multiple sclerosis

A failure in apoptosis of lymphocytes may lead to harmful immunoreactivity in MS. We analyzed apoptosis-related molecules including TRAIL, sFas, sFasL and MIF in the blood of 117 MS patients and controls to answer whether these molecules may be used in the evaluation of disease activity and immunomodulatory effect of IFN-beta. Increased levels of sTRAIL, sFasL and MIF were found in sera of untreated patients with MS relapse indicating their association with MS disease activity. IFN-beta treated patients in remission had increased TRAIL mRNA, sTRAIL, sFaL and MIF that most likely reflect bioactivity of IFN-beta.

Therapeutic activities of intravenous immunoglobulins in multiple sclerosis involve modulation of chemokine expression.

The objective of this study was to identify genes that are differentially expressed in peripheral T cells of patients with MS exacerbation receiving treatment with IVIG. Using microarray analysis, we identified 360 genes that were at least two-fold up- or down-regulated. The expression of four representative genes (PTGER4, CXCL5, IL11 and CASP2) was confirmed by quantitative PCR. Four of the differentially expressed genes encode chemokines (CXCL3, CXCL5, CCL13 and XCL2) that are involved in directing leukocyte migration. We suggest that the modulation of chemokine expression in peripheral T cells contributes to the beneficial activity of IVIG in patients with MS exacerbation.

Gene expression profiles in Finnish twins with multiple sclerosis

BackgroundSince 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.MethodsIn 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.ResultsIt 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.ConclusionOver 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.

Effect of high-dose methylprednisolone treatment on CCR5 expression on blood cells in MS exacerbation.

Objectives –  Therapy of acute exacerbations of multiple sclerosis (MS) with high‐dose intravenous methylprednisolone (IVMP) has shortened the recovery period after relapses, but the mechanisms responsible for the beneficial effects of IVMP in attacks have not been clearly established. Our purpose was to analyze the effect of IVMP on the expression of chemokine receptor 5 (CCR5) protein in blood in acute MS exacerbation.

Intravenous immunoglobulins are a therapeutic option in the treatment of multiple sclerosis relapse.

Objective:The objective of the study is to evaluate the efficacy and tolerability of intravenous immunoglobulin (IVIG) monotherapy in the treatment of multiple sclerosis (MS) relapse. Background:High-dose intravenous methylprednisolone (IVMP) and plasmapheresis have been shown to shorten the recovery period of an MS relapse. Options for those who have contraindications for or are unresponsive to these treatments are very limited. Intravenous immunoglobulin has been used experimentally in these situations, even though there are no previous studies on its efficacy as monotherapy in MS relapse. Subjects and Methods:Twelve consecutive MS patients with acute MS relapse were treated with IVIG 0.4 g/kg per day for 5 days, and the next 5 patients received IVMP 1000 mg/d for 3 days. Volumetric brain magnetic resonance imaging (MRI) and clinical evaluation using expanded disability status scale (EDSS) were performed at baseline and at 3 weeks after treatment. EDSS score after 1 year of the treatment was collected from the patient records. MRI evaluation was performed blindly but not the clinical examination and EDSS scoring. Results:A significant reduction in the volumes of T2-, fluid-attenuated inversion recovery-, and gadolinium-enhanced lesions was detected in the IVIG-treated group, but not in the IVMP-treated patients. The difference between the groups did not reach statistical significance. The EDSS score improved equally in both groups. Conclusions:Intravenous immunoglobulin did not show inferiority compared with IVMP in the treatment of an acute MS relapse evaluated clinically and radiologically. Therefore, we suggest that IVIG may be tried as a therapy in acute MS relapse, especially in case of contraindications to IVMP and plasmapheresis.

Increased disability and MRI lesions after discontinuation of IFN‐β‐1a in secondary progressive MS

Objective –  To examine neurological and magnetic resonance imaging (MRI) changes following discontinuation of interferon (IFN)‐β‐1a treatment in secondary progressive multiple sclerosis (SPMS).

Once‐weekly 22μg subcutaneous IFN‐β‐1a in secondary progressive MS: a 3‐year follow‐up study on brain MRI measurements and serum MMP‐9 levels

Objective –  To study the effect of weekly injected subcutaneous interferon (IFN)‐β‐1a 22 μg on the extent of brain lesions on magnetic resonance imaging (MRI) and the level of serum matrix metalloproteinase (MMP)‐9 in patients with secondary progressive multiple sclerosis (SPMS).

Volumetric MRI assessment of brain and spinal cord in Finnish twins discordant for multiple sclerosis.

Background and Objective. Brain size, white matter hyperintensity, and the development of brain atrophy are known to be highly heritable. The decrease of brain volume starts from the very onset of multiple sclerosis and is 10-fold compared with normal aging. The aim of this study was to assess whether the brain and spinal cord volumes and the volume of white matter lesions differed between twins with multiple sclerosis and their asymptomatic co-twins. Material and Methods. A co-twin control method was used to evaluate whether the brain and spinal cord volumes differ between twins with multiple sclerosis and their co-twins. Nineteen twin pairs were studied neurologically, and the volumes of T1, T2, FLAIR, and gadolinium-enhanced lesions and those of the brain and the spinal cord were obtained by magnetic resonance imaging. Results. Significant differences in the brain (P=0.064) or spinal cord (P=0.648) volumes were not detected. Four of the 7 monozygotic and 5 of the 12 dizygotic co-twins had focal brain white matter lesions, but none fulfilled the magnetic resonance imaging criteria of Barkhof. Spinal cord lesions were not seen in any of the co-twins. Conclusions. The absence of a significant difference in the brain or spinal cord volume between the twins with multiple sclerosis and their co-twins supports the recent observation of brain size and the development of brain atrophy being highly heritable.BACKGROUND AND OBJECTIVE Brain size, white matter hyperintensity, and the development of brain atrophy are known to be highly heritable. The decrease of brain volume starts from the very onset of multiple sclerosis and is 10-fold compared with normal aging. The aim of this study was to assess whether the brain and spinal cord volumes and the volume of white matter lesions differed between twins with multiple sclerosis and their asymptomatic co-twins. MATERIAL AND METHODS A co-twin control method was used to evaluate whether the brain and spinal cord volumes differ between twins with multiple sclerosis and their co-twins. Nineteen twin pairs were studied neurologically, and the volumes of T1, T2, FLAIR, and gadolinium-enhanced lesions and those of the brain and the spinal cord were obtained by magnetic resonance imaging. RESULTS Significant differences in the brain (P=0.064) or spinal cord (P=0.648) volumes were not detected. Four of the 7 monozygotic and 5 of the 12 dizygotic co-twins had focal brain white matter lesions, but none fulfilled the magnetic resonance imaging criteria of Barkhof. Spinal cord lesions were not seen in any of the co-twins. CONCLUSIONS The absence of a significant difference in the brain or spinal cord volume between the twins with multiple sclerosis and their co-twins supports the recent observation of brain size and the development of brain atrophy being highly heritable.