Search

Anti-myelin IgGs occur in the cerebrospinal fluid (CSF) and serum of multiple sclerosis (MS) patients, and can induce inflammatory effector functions in leukocytes by crosslinking IgG receptors (FcgammaR). The efficiency of FcgammaR-mediated inflammatory processes is affected by functional polymorphisms of three Fcgamma receptors (FcgammaRIIa, FcgammaRIIIa, FcgammaRIIIb). The relevance of FcgammaR polymorphisms in MS was evaluated by studying the distribution of FcgammaRIIa, FcgammaRIIIa and FcgammaRIIIb genotypes in 432 MS patients and 515 healthy controls. No significant differences were found between MS patients and controls, or between subgroups of patients. We conclude that Fcgamma receptor polymorphisms influence neither susceptibility nor clinical disease course of MS.

The balance between CD28 and CTLA-4 signalling is important for regulation of the immune response. We were interested whether a genetically mediated disturbance of this balance could be related to susceptibility or severity of multiple sclerosis (MS). We examined three polymorphisms in these genes, CTLA-4-318, CTLA-4+49 and CD28-I3+17, in 514 patients with MS and 181 controls. As the loci cannot be assumed independent of each other, we analysed the effects of each of the three polymorphisms corrected for the presence of the other two. We found no association between carriership of any of the alleles either with susceptibility to MS or with clinical features. For a subgroup of patients, longitudinal magnetic resonance imaging (MRI) data were available. We observed no effects of the polymorphisms on brain and lesion volumes. These data suggest that the polymorphisms under investigation do not affect the risk of developing MS and have no influence on the course of disease.

In the recently proposed diagnostic criteria for multiple sclerosis (MS) by McDonald, the modified magnetic resonance imaging (MRI) Barkhof criteria have been incorporated. We examined the validity of this implementation in the Early Treatment of MS study, a randomized, double-blind, placebo-controlled study of 22 microg interferon beta1a given subcutaneously once weekly in 309 patients with a first episode consistent with demyelinating disease (and abnormal MRI). Conversion to clinically definite MS (CDMS) within 2 years of follow-up, as evidenced by a new clinical episode, occurred in 41% of patients (independent of treatment) with gadolinium enhancement or nine or more T2 lesions versus 11% of those without either finding (p = 0.017); similarly, proportions converting were 44% versus 31% for infratentorial lesions (p = 0.026), 40% versus 35% for juxtacortical lesions (p = 0.413), and 41% versus 17% for three or more periventricular lesions (p = 0.034). The rate of conversion to CDMS based on the number of modified Barkhof criteria was 22% for two or fewer positive criteria, increasing to 47% with four positive criteria. For a cutoff of three positive criteria, the hazard ratio for time to CDMS was 2.3 (95% confidence interval, 1.17-4.55; p = 0.016). Treatment effect seemed more evident as the number of positive criteria increased, and the number of patients needed to avoid one patient converting to CDMS decreased from 50 in patients with one or two positive criteria to 5.6 in patients with four positive criteria. However, the study was not powered to detect statistically significant treatment by variable interaction, and this remains an important issue for further study.

Interleukin-1beta (IL-1beta) is present in multiple sclerosis (MS) lesions. Interleukin-1 receptor antagonist (IL-1Ra) moderates the induction of experimental autoimmune encephalomyelitis (EAE). Here, we show that families that are characterized by high IL-1beta over IL-1Ra production ratio are at 2.2-fold (95% CI, 1.0-4.8; p=0.05) increased risk to have a patient relative with relapse-onset MS than families with a low ratio. It is also related to the reduction of volumetric magnetization transfer ratio (MTR) histogram height, a measure of parenchymal integrity (p=0.04). Those families who combine a high IL-1beta over IL-1Ra ratio with a high tumor necrosis factor (TNF) over IL-10 production ratio have a 6.2-fold (95% CI, 1.8-21; p=0.002) increased risk. Innate production of IL-1beta and IL-1Ra is not related to the outcome of primary progressive MS. Taq1 polymorphism in the IL-1beta gene and the variable number of tandem repeats (VNTR) polymorphism of 86-base pairs within the IL-1Ra gene cannot explain these findings.

Interleukin-10 (IL-10) secretion affects the inducibility of experimental autoimmune encephalomyelitis and the outcome of multiple sclerosis (MS). Here, we report that a G to A polymorphism in the IL-10 promoter at position -2849 is significantly associated with low IL-10 production. The frequency of this polymorphism is lower among patients with primary progressive compared with patients with relapse-onset MS and control persons.

Objective: To prospectively characterize the relation between 1-year changes in neurologist ratings of abnormalities as measured by means of the Expanded Disability Status Scale (EDSS) and changes in observations of functional impairment as measured by means of the Multiple Sclerosis Functional Composite (MSFC) in the clinical assessment of multiple sclerosis (MS)., Methods: One hundred twenty patients with MS were recruited at our outpatient clinic. Impairment and disability at baseline and follow-up were assessed using the EDSS and MSFC. We studied correlations between change (Delta) in the EDSS, MSFC, and MSFC components for the total population and different subgroups and analyzed the contribution of change in MSFC components to change in the EDSS and MSFC., Results: Median EDSS score at baseline was 4.5; at follow-up, 5.0. Mean MSFC score at baseline was -0.00; at follow-up, -0.04. Good cross-sectional correlations were found between the EDSS and MSFC at baseline (-0.72) and follow-up (-0.73). Only weak correlations were found between DeltaEDSS and DeltaMSFC. Although DeltaEDSS showed the strongest correlations with change in leg function and weak or no correlation with change in cognitive function or arm function, DeltaMSFC showed the highest correlation with change in arm function and cognitive function., Conclusion: Our longitudinal data indicate that the MSFC reflects change from different dimensions of neurologic functions, which is a favorable characteristic when compared with the EDSS.