Multiple Sclerosis
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Pubmed
Journal: BMJ case reports
December/12/2016
Abstract
We describe three cases of patients with concomitant acute medullary or brainstem multiple sclerosis (MS) lesions and detectable spinal fluid varicella-zoster virus DNA. Herpes simplex virus PCR was also positive in two of the patients. One patient was re-punctured 2 weeks following the relapse, with negative results. The PCR findings greatly delayed correct diagnosis and treatment in all three patients. Based on our cases, we propose that inflammatory medullary and brainstem lesions could result in viral leakage, and possibly viral reactivation, from destroyed sensory neurons, yielding false-positive cerebrospinal fluid PCR results. As this can have diagnostic and therapeutic consequences, further studies are warranted to evaluate the clinical relevance of these findings.
Pubmed
Journal: Journal of neuroimmunology
September/11/1996
Abstract
Activation of complement is critically involved in inflammatory reactions in both Guillain-Barré syndrome (GBS) and multiple sclerosis (MS). Soluble human complement receptor 1 (sCR1) blocks complement activation by both classical and alternative pathways. We studied serum and cerebrospinal fluid (CSF) concentrations of sCR1 in 23 patients with GBS, 27 patients with MS and 30 controls. No significant differences were found between patients and controls. Transient liver affection probably caused high serum sCR1 levels in two patients with GBS. The serum and CSF sCR1 levels were not correlated to the disease activity of GBS and MS, nor to the relapsing-remitting or chronic-progressive forms of MS. In GBS the CSF sCR1 levels correlated with the CSF total protein concentrations (r = 0.9, P < 0.01), suggesting that sCR1 leaks from serum into CSF via a damaged blood-nerve barrier. The serum sCR1 levels in GBS were slightly higher than in MS (P < 0.05). Whether this reflects changes in the release or consumption of sCR1 in these patients is at present unknown.
Pubmed
Journal: Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology
January/15/2012
Abstract
Multiple sclerosis (MS) may be associated with reduced bone mass and higher frequency of osteoporosis. Femoral and spinal bone mineral density (BMD) in 70 ambulatory MS patients (46 females and 24 males) was compared with 100 sex-, age-, and BMI-matched control individuals. BMD was reduced in male patients (lumbar spine 0.976 ± 0.114 g/cm(2) compared with 1.059 ± 0.147 g/cm(2) in controls, p = 0.024, total hip 0.946 ± 0.136 g/cm(2) compared to 1.036 ± 0.118 g/cm(2) in controls, p = 0.008, femoral neck 0.812 ± 0.136 g/cm(2) compared with 0.887 ± 0.135 g/cm(2) in controls p = 0.042), and only in the total hip in female patients (0.88 ± 0.127 g/cm(2) compared with 0.935 ± 0.112 g/cm(2) in controls, p = 0.018). Multivariate analysis demonstrated that the predominantly affected site was the hip. MS patients exhibit increased frequency of low bone mass compared with controls. Further studies should assess the etiologic factors and employ appropriate therapies.
Pubmed
Journal: Drug news & perspectives
May/5/2004
Abstract
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterized by the destruction of the myelin sheath surrounding axons. On the basis of data from the animal model, experimental autoimmune encephalomyelitis (EAE) and the detection of myelin-reactive cells in MS patients, this destruction is thought to be due to an autoimmune T-cell-mediated response to myelin antigens. Until recently, the characterization of T-cell recognition of myelin antigens has necessarily focused on the response to myelin proteins. However, the discovery of CD1-mediated presentation of lipids and glycolipids to a variety of T-cell populations has greatly expanded the repertoire of antigens to which T cells can respond. Studies in the EAE model suggest a role for myelin lipids in disease pathogenesis. Recent characterization of the expression and function of CD1 and the responding T-cell populations does support a role for this pathway in the disease process. Furthermore, data suggest that it may be possible to modulate the disease course by targeting this pathway. Characterization of CD1-mediated presentation of lipids to T cells has only recently been investigated in MS, with most attention focusing on the expression of group I CD1 proteins in MS lesions. In light of data from the animal model, further characterization of the expression and function of group I and group II CD1 proteins is warranted, and could lead to the development of effective therapies to treat MS.
Pubmed
Journal: Journal of neuroimmunology
July/2/1997
Abstract
To identify a panel of multiple sclerosis patients (MS) for a phase I clinical trial of a T-cell receptor (TCR) peptide vaccine we characterized the T-cell populations present in the cerebrospinal fluids (CSF) of a large group of patients with respect to surface phenotype and state of activation, TCR beta chain utilization, features of the CDR3 junctional region, the extent of clonality and persistence of selected clonotypes over time. These CSF cell populations consist of approximately 60% CD4+ T-cells, half of which bear IL-2 receptors, indicating these activated T-cells may be part of the pathogenic process in MS. When these activated CD4+ T-cells were selectively expanded in IL-2/IL-4 supplemented cultures, an over-representation of several TCRV beta families was noted in 39/47 patients, the most frequent being V beta 6.5, V beta 6.7, V beta 2, V beta 5 and V beta 4. Biased expression of various members of the V beta 6 family was seen in 21 of this group of 39 patients. Clonal analysis of TCR beta 6 CDR3 sequences, revealed two notable features: clonal dominance and clonal persistence. CSF cells from two-thirds of MS patients contained a dominant clone comprising 50% or more of sequences and the same patient-specific clone could be shown to persist for up to 18 months. This clonal prevalence and over representation of V beta 6+TCR raises the possibility that immunization with a V beta 6 peptide vaccine may produce a regulatory immune response leading to a clinical benefit.
Pubmed
Journal: AJNR. American journal of neuroradiology
December/11/1995
Abstract
OBJECTIVE
To investigate the relationship between the appearance of multiple sclerosis lesions identified on unenhanced T1-weighted images and their corresponding magnetization transfer ratios.
METHODS
A total of 119 white matter lesions seen on T2-weighted images in 17 patients with multiple sclerosis were evaluated. Axial T1-weighted images were used to classify the lesions as isointense to white matter (10 lesions), hypointense to white matter but hyperintense to gray matter (44 lesions), hypointense to gray matter (59 lesions), and relatively isointense to cerebrospinal fluid (6 lesions). The magnetization transfer ratio of each lesion was calculated, and an average magnetization transfer ratio for each subcategory was determined.
RESULTS
The magnetization transfer ratio values became progressively lower with increasing hypointensity of lesions on T1-weighted images. The average magnetization transfer ratio for lesions isointense to white matter, hypointense to white matter but hyperintense to gray matter, hypointense to gray matter, and relatively isointense to cerebrospinal fluid was 34.90 +/- 2.67 mean +/- SD), 30.93 +/- 3.57, 27.27 +/- 3.56, and 23.62 +/- 2.83, respectively. All groups were significantly different from each other.
CONCLUSIONS
Lesions isointense to white matter exhibited higher magnetization transfer ratio values than lesions that were hypointense. These findings are consistent with relative preservation of the myelin structure in the former, perhaps indicating that these lesions are predominantly inflammatory (edematous) in nature. The proportionately lower magnetization transfer ratio values of lesions that appear progressively more hypointense on T1-weighted images may reflect varying degrees of demyelination, with increasing lesion hypointensity corresponding to more breakdown in the macromolecular structure. These results suggest that T1-weighted images may be useful in characterizing the underlying pathologic substrate in multiple sclerosis plaques.
Pubmed
Journal: Electroencephalography and clinical neurophysiology
December/17/1980
Abstract
Visual cortical potentials were evoked by reversal of a checkerboard pattern and a small quadrangular foveal stimulus. Examination of 68 patients with MS showed the highest detection rate for abnormality of VEPs with a combination of both methods. Follow-up studies revealed changes (improvement or impairment) of VEP amplitudes or latencies in nearly half of the patients. Most of the changes were correlated with a history of acute optic neuritis. For the detection of changes the foveal stimulus is preferable to the checkerboard pattern.
Pubmed
Journal: Journal of neuroimaging : official journal of the American Society of Neuroimaging
December/11/2002
Abstract
Despite good clinical criteria for diagnosing optic neuritis (ON), only a few techniques can precisely assess its impact on visual brain function. The authors studied whether functional magnetic resonance imaging (fMRI) of visual activation reliably reflects the cerebral consequences of acute unilateral ON, and how fMRI correlates with clinical function and visual evoked potentials (VEPs). Twenty ON patients, before and after steroid treatment, were compared to 20 controls. Each eye was stimulated separately with a checkerboard pattern reversing at 1, 2, 4, and 8 Hz. VEPs were recorded the same day. Initially, affected eye responses differed significantly from those of unaffected counterparts and controls in 12 patients. Post hoc classification by fMRI criteria was correct in approximately 85%. fMRI and VEP response parameters (as well as visual acuity) correlated significantly. The higher stimulation frequencies yielded greater fMRI responses from unaffected eyes, but not from affected eyes, in controls. The fMRI responses were quantifiable in every subject, whereas in 11 ON eyes, no VEPs were obtained during the acute stage. The authors conclude that fMRI is sensitive to the cerebral response alteration during ON and might therefore contribute to evaluating the temporal evolution of the visual functional deficit during recovery or therapy.
Pubmed
Journal: Neuroimaging clinics of North America
March/2/2009
Pubmed
Journal: Drugs
May/1/2017
Abstract
Recent times have seen an increase in the number of options to treat multiple sclerosis. Ocular manifestations of multiple sclerosis are well known to treating physicians; however, the medications used to treat multiple sclerosis can also have ocular side effects. This review article focuses on the ocular manifestations of corticosteroids and disease-modifying agents such as interferon, fingolomod, natalizumab, alemtuzumab and mitoxantron used to treat the disease. The ocular manifestations of multiple sclerosis treatments can be varied depending on the drug used, and include retinopathy, chronic central serous chorioretinopathy, macular oedema, Graves' ophthalmopathy and cortical blindness. These effects may be specific to the drug or secondary to their immunosuppressive effect. The association of macular oedema with fingolomod is clear and merits ocular screening for toxicity. The immunosuppressive nature of the treatments makes patients prone to acquired infections. Hence, if a patient with multiple sclerosis presents with vision loss, infectious and drug-induced aetiology should be considered alongside relapses of multiple sclerosis itself as a cause.
Pubmed
Journal: Immunology today
August/16/1989
Abstract
The precise role of T cells in multiple sclerosis (MS) remains to be defined. No MS-specific antigen has been found. The autoimmune hypothesis for MS rests on immune changes seen in the spinal fluid and brain and on the demonstration, in an experimental animal model, that T cells raised to myelin basic protein transfer demyelination. In this review, Virginia Calder and colleagues focus on recent studies suggesting that in MS, the initial T-cell response occurs within the central nervous system and that the blood poorly reflects this immune activity. This contrasts with the animal model, experimental allergic encephalomyelitis, where the initial immune response is peripheral.
Pubmed
Journal: Journal of autoimmunity
March/7/2007
Abstract
The identification of disease related autoantigens targeted by pathogenic T- and B-cell responses is crucial for the development of improved therapies for autoimmune diseases. To identify immunogenic targets recognized by the humoral immune response, we have recently applied a novel and powerful molecular approach, named 'serological antigen selection' (SAS). This method involves the display of a cDNA expression library on filamentous phage and subsequent selection on patient immunoglobulin G (IgG). In the present study, we have cloned a cDNA repertoire from a multiple sclerosis (MS) patient in pVI phage display vectors and performed selections on pooled MS cerebrospinal fluid (CSF) samples immobilized with anti-human IgG. To further streamline this procedure, we report an optimized SAS procedure in which we have successfully established methods for enrichment of MS-specific candidate antigens. In conclusion, the broad applicability of the SAS method makes it a highly promising method for investigating the autoimmune repertoire.
Pubmed
Journal: Lupus
March/31/2008
Abstract
Although both multiple sclerosis (MS) and systemic lupus erythematosus (SLE) are relatively common autoimmune disorders, especially in young women and often coexist in families, they are only rarely reported to coexist in a single patient. We here present a case of a young woman with a history of MS from many years who diagnosed as suffering as well from SLE.
Pubmed
Journal: Journal of neuroimmunology
April/11/2001
Abstract
Polyspecific immunoglobulins (IVIg) have been shown to reduce disease activity in multiple sclerosis (MS). To investigate the mechanisms of action of IVIg, we studied the impact of IVIg on growth and death (apoptosis) of human (auto)antigen-specific T cells. We observed a substantial suppression of proliferation of specifically activated T cells, in absence of caspase activation or DNA fragmentation. Further, neither susceptibility of T cells to undergo CD95-mediated apoptosis nor expression of apoptosis-blocking bcl-2 was modulated by IVIg. We conclude that IVIg may inhibit the reactivity of antigen-specific T cells in MS through suppression of proliferation rather than modulation of apoptosis.
Pubmed
Journal: Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology
June/27/2001
Abstract
OBJECTIVE
To quantify the percentage of motor units of a foot muscle that can be activated by transcranial magnetic stimulation (TMS) in normal subjects and patients.
METHODS
We adapted the recently described triple stimulation technique (TST) for recordings from abductor hallucis (AH). Conventional motor evoked potentials (MEPs) of this muscle are usually small and variable in shape, because of an important temporal desynchronization of the TMS induced spinal motor neuron discharges. The TST allows 'resynchronization' of these discharges and thereby a quantification of the proportion of motor units activated by TMS. The lower limb (LL-) TST was applied to 33 sides of 18 normal subjects and 51 sides of 46 patients with multiple sclerosis, amyotrophic lateral sclerosis, or spinal cord disorders.
RESULTS
In healthy subjects, the LL-TST demonstrated that TMS achieves activation of virtually all motor neurons supplying the AH. In 33 of 51 patient sides, abnormal LL-TST responses suggested corticospinal conduction failures of various degrees. The LL-TST was 2.54 times more sensitive to detect central conduction failures than the conventional LL-MEPs. Combining the LL-TST with TST of the upper limbs further increased the sensitivity to detect a conduction failure by 1.50 times.
CONCLUSIONS
The LL-TST markedly improves the examination of corticospinal pathways.
Pubmed
Journal: Phlebology
December/21/2011
Abstract
Chronic cerebrospinal venous insufficiency (CCSVI) is a hypothesis through which cerebral venous drainage abnormalities contribute towards the pathogenesis of multiple sclerosis. CCSVI venoplasty is already practised worldwide. We report the case of a 33-year-old lady with multiple sclerosis who underwent left internal jugular venoplasty resulting in iatrogenic jugular thrombosis requiring open thrombectomy for symptom relief. This occurred without insertion of a stent and while fully anticoagulated. Clinicians should be aware that endovenous treatment of CCSVI could cause paradoxical deterioration of cerebral venous drainage. Patients with complications post venoplasty are now presenting to geographically distant vascular units.
Pubmed
Journal: The Clinical journal of pain
July/29/2007
Abstract
OBJECTIVE
Central neuropathic pain occurs in around 28% of patients with multiple sclerosis (MS). The Neuropathic Pain Scale (NPS) has received preliminary validation in peripheral neuropathic pain conditions. The aim of this study was to validate its use in MS central pain syndromes.
METHODS
We administered the NPS to 141 patients with MS, together with the Short Form McGill Pain Questionnaire (SFMPQ), the Hospital Anxiety and Depression Scale (HADS), and Short Form 36 Health Survey (SF-36).
RESULTS
Cronbach's alpha was 0.78 (95% CI 0.69; 0.83), implying a high degree of internal consistency. Three factors, "Familiar," "Superficial," and "Alien Perception," were extracted, accounting for 64% of the variance. The NPS 10-item total correlates with: the SFMPQ 15-item total score, rho=0.63 (95% CI 0.49; 0.74), its Visual Analog Scale, rho=0.49 (95% CI 0.33; 0.64), the transformed Pain domain of the SF-36 rho=-0.49 (95% CI -0.63; -0.32), but not with its remaining seven health domains, or with either the HADS anxiety or the depression scores. Limits of agreement for short-term test or re-test reliability of the 100 point NPS total (median 2 days, range 1 to 7) were -12 to 14 and when administered to 78 patients who rated their neuropathic pain the "Same" [median interval 33 days (range 19 to 126), the long-term test or re-test correlation coefficient was 0.71 (95% CI 0.6; 0.79)].
CONCLUSIONS
The NPS appears a useful tool in the assessment of neuropathic pain in MS patients and possibly in measuring outcomes of therapeutic interventions.
Pubmed
Journal: Multiple sclerosis (Houndmills, Basingstoke, England)
October/19/1999
Abstract
Evoked potentials (EPs) have been widely utilised in Multiple Sclerosis (MS) patients to demonstrate the involvement of sensory and motor pathways. Their diagnostic value is based on the ability to reveal clinically silent lesions and to objectivate the central nervous system damage in patients who complain frequently of vague and indefinite disturbances which frequently occurs in the early phases of the disease. The advent of magnetic resonance imaging (MRI) techniques has greatly reduced the clinical utilisation of EPs, which is not fully justifiable, as the information provided by EPs are quite different from those provided by MRI. The abnormalities of evoked responses reflect the global damage of the evoked nervous pathway and are significantly correlated with the clinical findings, while the vast majority of MRI lesions are not associated to symptoms and signs. Transversal and longitudinal studies have demonstrated that EP changes in MS are more strictly related to disability than MRI lesion burden. On the contrary, MRI is more sensitive than EPs in revealing the disease activity. Evoked responses modifications observed in MS are not disease-specific; moreover longitudinal studies showed latency and morphology changes of evoked responses not always related to clinical changes. Such a dissociation can be explained both by technical factors and by subclinical disease activity. To reduce the negative impact of technical aspects, only reproducible parameters of the evoked responses should be used to monitor disease evolution and therapeutic interventions.
Pubmed
Journal: Expert opinion on therapeutic patents
February/11/2013
Abstract
BACKGROUND
The JAK family comprises of the four non-receptor tyrosine kinases JAK1, JAK2, JAK3 and Tyk2, which play key, but differing, roles in cytokine receptor signal transduction. A non-selective JAK inhibitor, ruxolitinib, has recently been approved to treat myelofibrosis whereas tofacitinib is poised for approval to treat rheumatoid arthritis. Selective inhibition of JAK3, JAK1 or Tyk2 provides the opportunity to achieve clinical efficacy in the treatment of inflammatory diseases while reducing the risk of dose-limiting effects attributable to JAK2 inhibition.
METHODS
This review considers the small number of published patent filings that claim either selective JAK1 or selective Tyk2 inhibitors. These are considered in the context of the considerably larger number of disclosures and patent filings claiming selective JAK2 or JAK3 inhibitors.
CONCLUSIONS
The recent disclosure of the clinical efficacy of a selective JAK1 inhibitor (GLPG-0634) in rheumatoid arthritis and detailed disclosure of the some potent and highly selective JAK1 inhibitors provide a clear stimulus for further activity in this area. The availability of a selective Tyk2 inhibitor will provide the opportunity for better understanding of the physiological role of this kinase. Recent patent applications indicate that Tyk2 selectivity is achievable and Tyk2 inhibitors have potential in the treatment of multiple sclerosis.
Pubmed
Journal: Journal of neuroimmunology
August/21/2005
Abstract
ADAMTS14 is a novel member of the ADAMTS (a disintegrin-like and metalloproteinase domain with thrombospondin type 1 modules) metalloproteinase family which processes extracellular matrix proteins. In the present study we performed a comprehensive investigation of the ADAMTS14 as a candidate gene for susceptibility to multiple sclerosis (MS). Eight single nucleotide polymorphisms (SNPs) were analyzed in a case-control study of 287 patients with MS [192 with relapsing-remitting MS (RRMS) and 95 with primary-progressive MS (PPMS)], and 285 age- and sex-matched controls. Allele and genotype frequencies were compared between controls and the MS subgroups, and gene-based haplotypes were reconstructed by computational procedures. Pairwise linkage disequilibrium values (D') suggested that three locus pairs (SNPs 3 through 5) had alleles in strong disequilibrium and constituted a haplotype block spanning 14 kb. Overall comparisons of allele and genotype frequencies showed association for SNPs 3 and 6 with MS. Stratification of MS patients according to major clinical forms revealed an increased frequency of both allele C (p = 0.006) and CC homozygosity (p = 0.008) at SNP6 in RRMS patients compared with controls. PPMS was associated with allele A at SNP2 compared with RRMS (p = 0.003) and controls (p = 0.009), and with CG heterozygosity at SNP3 compared with controls (p = 0.005). Haplotype frequency comparisons showed significant association between PPMS and the AGGGC haplotype compared with controls (p = 0.0004), and negative association between RRMS and the GGAGT haplotype compared with controls (p = 0.0026). No association was detected between different genotypes and disease severity measured by the Multiple Sclerosis Severity Score (MSSS). These findings suggest a potentially important role for the ADAMTS14 gene in predisposition to MS.
Pubmed
Journal: Multiple sclerosis (Houndmills, Basingstoke, England)
February/3/2009
Abstract
OBJECTIVE
We hypothesized that autoaggressive immune responses observed in multiple sclerosis (MS) could be associated with an imbalance in proportion of immune cell subsets and in cytokine production in response to infection, including viruses.
METHODS
We collected blood mononuclear cells (MNC) from 23 patients with MS and 23 sex- and age-matched healthy controls (HC) from the island of Sardinia, Italy, where the prevalence of MS is extraordinarily high. Using flow cytometry, we studied MNC for expression of blood dendritic cell antigens (BDCA)-2 and BDCA-4 surface markers reflecting the proportion of plasmacytoid dendritic cells (pDC) that produce type I interferons (IFNs) after virus challenge and promote Th2/anti-inflammtory cytokine production. In parallel, pro-inflammatory (interleukin [IL]-2, IL-12, IFN-gamma), anti-inflammatory (IL-4, IL-10), and immuno-regulatory/pleiotropic cytokines (type I IFNs including IFN-alpha and beta, IL-6) were measured before and after an in vitro exposure to herpes simplex virus type 1 (HSV-1).
RESULTS
The subset of lineage negative (lin(-)), BDCA-2(+) cells was lower in patients with MS compared with HC (0.08 + or - 0.02% vs 0.24 + or - 0.02%; P < 0.001). A similar pattern was observed for lin(-)BDCA-4(+) cells (0.08 + or - 0.02% vs 0.17% + or - 0.03; P < 0.01). Spontaneous productions of IL-6 (45 + or - 10 pg/mL vs 140 + or - 26 pg/mL; P < 0.01) and IL-10 (17 + or - 0.4 pg/mL vs 21 + or - 1 pg/mL; P < 0.05) by MNC were lower in patients with MS compared with HC. Spontaneous production of IL-6 (6.5 + or - 0.15 pg/mL vs 21 + or - 5 pg/mL; P < 0.01 and IL-10 (11 + or - 1 pg/mL vs 14 + or - 3 pg/mL; P < 0.05) by pDC was also lower in patients with MS compared with HC. Exposure of MNC to HSV-1 showed, in both patients with MS and HC, increased production of IFN-alpha, IL-6, and IL-10 but decreased production of IL-4. In response to HSV-1 exposure, productions of IL-6 (165 +or - 28 pg/mL vs 325 + or - 35 pg/mL; P < 0.01) and IL-10 (27 +or - 3 vs 33 + or - 3 P < 0.05) by MNC as well as by pDC (IL-6: 28 + or - 7 vs 39 + or - 12 P < 0.05; IL-10: 14 + or - 1 vs 16 + or - 3 P < 0.05) were lower in patients with MS compared with HC.
CONCLUSIONS
The results implicate a new evidence for altered immune cells and reduced immune responses in response to viral challenge in MS.
Pubmed
Journal: Multiple sclerosis (Houndmills, Basingstoke, England)
May/3/2005
Abstract
Cerebral venous thrombosis (CVT) has been described in several cases of clinically definite multiple sclerosis (MS). In the majority of these, lumbar puncture followed by intravenous corticosteroid treatment was suspected as the cause. We report what is, to our knowledge, the first case of a patient with a multifocal clinically isolated syndrome suggestive of MS onset, who developed multiple CVT after lumbar puncture and during high-dose i.v. corticosteroid treatment We conclude that the sequence 'lumbar puncture followed by corticosteroid treatment' may be a contributory risk factor for the development of CVT when associated with other risk factors.
Pubmed
Journal: Neurobiology of aging
April/22/2013
Abstract
Neuroimaging measures hold promise for enhancing the detection of disease-related genetic variants. In this study, we use advanced multivariate regression methods to assess the predictive value of single nucleotide polymorphisms (SNPs) on several brain volumetric- and lesion-related neuroimaging measures in a well-characterized cohort of 326 patients with multiple sclerosis (MS). SNP selection was constrained to key epigenetic regulatory genes to further explore the emerging role of epigenetics in MS. Regression models consistently identified rs2522129, rs2675231, and rs2389963 as having among the highest predictive values for explaining differences related to brain volume measures. These SNPs are all contained in genes from the same superfamily, histone deacetylases, which have biological functions that are relevant to MS, neurodegeneration, and aging. Our preliminary findings generate hypotheses for testing in future independent MS data sets as well as other neurodegenerative conditions.
Pubmed
Journal: Journal of immunology (Baltimore, Md. : 1950)
April/1/2004
Abstract
To date, none of the myelin-associated Ag targets definitively discriminates between the immune response observed in multiple sclerosis (MS) patients and healthy subjects. However, it has been shown recently that analysis of global immune Ab profiles such as natural autoantibody reactivities can help to distinguish between normal individuals and patients suffering from various immune diseases. The aim of our study was to compare the global IgG immune response against brain self-Ags in sera from 82 MS patients and 27 healthy subjects. The analysis of the immune profiles was performed by Western blotting, and data were subjected to linear discriminant analysis. Particular patterns of IgG reactivity were found in healthy subjects, Sjögren patients, and MS patients. Moreover, this approach separated the three clinical forms of MS with a high concordance rate with the clinical data (kappa value, 77.8%). Our study suggests, for the first time, that serum IgG Ab repertoires are able to distinguish MS patients. In addition, our data suggest that patterns of IgG reactivity could model the pathological processes underlying the various forms of MS. Further characterization of such discriminant Ags could provide useful information regarding their potent role in pathogenesis or regulatory processes in MS.
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