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Patrick Vermersch

Publications and source records attributed to Patrick Vermersch.

16 recordsLinked to original sources
PubMed2006

Changes in self-reactive IgG antibody repertoire after treatment of experimental autoimmune encephalomyelitis with anti-allergic drugs.

We reduced EAE severity by using two anti-allergic drugs. A control group of mice received i.p. injections of PBS as vehicle while a further two groups were treated either with pyrilamine, a histamine receptor 1 antagonist or with CV6209, a platelet activating factor receptor antagonist. Our results showed that the blockade of the responses to both histamine and PAF leads together to a decline in clinical signs of EAE and significant changes in the serum IgG recognition of some healthy brain antigenic targets. We characterized two discriminant antigens: internexin neuronal intermediate filament protein, and malate dehydrogenase 1, which were able to clearly distinguish untreated mice from treated mice. Their role as potent targets in pathogenic and/or neuroprotective processes is discussed.

Animals↗
PubMed2006

Diversified serum IgG response involving non-myelin CNS proteins during experimental autoimmune encephalomyelitis.

We sequentially analyzed the serum IgG response against normal mouse brain during experimental autoimmune encephalomyelitis in SJL/J mice injected with CFA, Bordetella pertussis toxin (BPT) and proteolipid protein 139-151 peptide, compared with mice that received CFA and BPT or were uninjected. Dynamic changes were observed from day 0 to day 28 in the 3 groups. Six highly discriminant antigenic bands (kappa=0.974) were identified. Three non-myelin proteins were characterized (mitochondrial aconitase hydratase 2, phosphoglycerate mutase 1, brain specific pyruvate deshydrogenase). The IgG response against two of them was less frequent in EAE whereas it was associated with multiple sclerosis in our previous work.

Aconitate Hydratase↗
PubMed2006

Relapsing sensorimotor neuropathy with ophthalmoplegia, antidisialosyl antibodies, and extramembranous glomerulonephritis.

A 72-year-old man presented with oculomotor dysfunction, subacute relapsing sensorimotor neuropathy, elevated erythrocyte sedimentation rate, IgM monoclonal paraprotein, cold agglutinins, and antidisialosyl IgM antibodies, features previously described by the acronym CANOMAD (chronic ataxic neuropathy with ophthalmoplegia, M protein, agglutination, and disialosyl antibodies). The patient also had extramembranous glomerulopathy associated with this syndrome. Treatment with corticosteroids improved both the neuropathy and glomerulopathy. This case suggests that the spectrum of neuropathy associated with monoclonal gammopathy may be broader than originally believed.

Action Potentials↗
PubMed2006

Myelopathies secondary to Sjögren's syndrome: treatment with monthly intravenous cyclophosphamide associated with corticosteroids.

OBJECTIVE: Central nervous system manifestations in Sjögren's syndrome (SS) include focal deficits, optic neuritis, and myelopathies. Acute and chronic myelopathies are frequently severe and sometimes respond poorly to corticosteroids. The efficacy of intravenous (IV) cyclophosphamide (CYC) has been suggested in single case reports. METHODS: We describe the potential usefulness of IV CYC in SS patients with severe myelopathies. Fourteen patients [with acute (n = 6) and chronic (n = 8) myelopathies] were treated with monthly CYC infusions (700 mg/m2) in addition to 500 mg of corticosteroids for one year. We evaluated the disability before and after CYC treatment using a walking distance calculation and the Expanded Disability Status Scale (EDSS). RESULTS: CYC treatment was well tolerated in all cases without serious adverse events. Nine patients (including the 6 with acute myelopathy) were improved after CYC treatment. Three patients were stabilized and 2 patients with chronic myelopathies had moderate progression of disability. The mean walking distance increased from 48.2 m before to 180.4 m after CYC treatment (p < 0.02). Mean EDSS score decreased from 6.6 to 5.7 (not significant). We found a correlation between the length of time before CYC treatment and clinical improvement for both the walking distance (p < 0.02) and the EDSS score (p < 0.05). CONCLUSION: Although a randomized multicenter controlled study is warranted to confirm our findings, IV CYC infusions seem to be useful for the treatment of myelopathies secondary to SS, particularly in acute but also in progressive cases. This treatment should be strongly considered as soon as possible when disease progression is observed.

Acute Disease↗
PubMed2005

New insights into cell responses involved in experimental autoimmune encephalomyelitis and multiple sclerosis.

Animal models of autoimmune diseases such as experimental autoimmune encephalomyelitis (EAE) are inflammatory demyelinating diseases which comprise a heterogeneous group of disorders that affect the peripheral and central nervous systems. EAE presents close similarities with multiple sclerosis (MS), a chronic inflammatory disease affecting central nervous system (CNS) white matter. Many studies have shown EAE to be a particularly useful animal model for the understanding of both the mechanisms of immune-mediated CNS pathology and the progressive clinical course of multiple sclerosis. Previous data has underlined the importance of CD4+ T cell involvement in mediating the autoimmune processes associated with the destruction of myelin and the role of the T helper 1 (Th1) pattern of cytokine secretion. However, EAE studies have also demonstrated that other cells involved in innate and/or adaptive immune responses may also play a critical role in the early and progressive events of the immune reaction leading to inflammation and CNS damage. In this review, we present such new data and discuss their potent implication for future new therapeutical approaches.

Animals↗
PubMed2004

Concomitant therapy for multiple sclerosis.

Interferon beta (IFNbeta) is the first-line treatment for patients diagnosed with multiple sclerosis (MS). In patients with MS who experience breakthrough disease while receiving treatment with IFNbeta, it is common clinical practice to administer additional therapeutic agents. The rationale for use of concomitant therapies in the long-term management of MS is derived from the heterogeneous and multifactorial etiology of this disease. Agents used concomitantly have the potential to exert synergistic effects and slow the progression of disease in patients who experience breakthrough disease. Concomitant therapies that have been reported in patients with MS are reviewed here.

Drug Therapy, Combination↗
PubMed2004

[Are there arguments for initiating an etiological treatment at the onset of the first demyelinating episode?].

The arrival of immunomodulating treatments The pathology of multiple sclerosis (MS) took benefit from progresses of magnetic resonance-based and immunological studies, leading to the introduction of immunomodulatory agents and notably interferon beta (IFNbeta). The therapeutic impact of such treatments in the relapsing-remitting forms of the disease, and our improved knowledge on the natural history of the disease, raise the possibility of treating patients after the first demyelinating episode. This strategy may be more relevant in patients presenting poor prognostic criteria. Magnetic resonance imaging (MRI) data The clinical characteristics of the first episode do not help to predict the mean or long term progression. Magnetic resonance imaging has shown that the progression of the disease is partly infra-clinical. Other than data revealing demyelination involvement and inflammation, MRI has also provided arguments suggesting early axonal distress. In a patient, the presence of high lesion load at onset on weighted T2 sequences, of black holes and gadolinium enhancing lesions s on T1 sequences, or the presence of new lesions on MRI conducted a few Months later are all predictive factors of clinical progression and suggest that treatment should be initiated early. The interest of interferon beta Two clinical trials have shown that treatment with IFNbeta treatment after a first demyelinating event significantly decreased the risk of a second episode in the short term. The aim of such treatment would be to limit the irreversible axonal lesions, notably in the form of axonal sections often associated with inflammatory lesions. An early reduction in the inflammatory response could lead to a lesser number of axons and, consequently, reduced clinical disability.

Adjuvants, Immunologic↗
PubMed2004

Distortion of the self-reactive IgG antibody repertoire in multiple sclerosis as a new diagnostic tool.

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.

Adult↗
PubMed2004

New antigenic candidates in multiple sclerosis: identification by serological proteome analysis.

Myelin antigen targets that are clearly associated with pathogenic events in multiple sclerosis (M.S.) patients remain to be defined. We recently demonstrated that the analysis of global IgG antibody response against human brain antigens using one-dimensional (1-D) immunoblotting, allowed us to discriminate M.S. patients from controls (both healthy subjects and patients with Sjögren's syndrome). Additionally, this approach also differentiated the three clinical forms of M.S. Indeed, 42 brain antigenic bands (26 from healthy brain and 16 from the M.S. brain) showed the discriminant IgG immune responses. The aim of our study was to characterize the 26 discriminant antigenic bands detected in healthy brain. Protein identification was successively performed by 1-D and two-dimensional (2-D) immunoblottings using sera from 18 M.S. patients, followed by mass spectrometry (MS) analysis and a database search. One hundred and two antigenic spots were then detected on 2-D immunoblots, with M.S. sera against healthy brains. Sixty-four spots were successfully matched with 2-D Coomassie brillant blue stained gels, which were further selected for MS analysis and annotated leading to the identification of 14 of the 26 discriminant antigens. Thus, serological proteome analysis may provide a useful tool for the identification of potentially new M.S.-associated antigens, whose relevance to physiopathological events remains to be defined.

Adult↗
PubMed2004

Neurologic manifestations in primary Sjögren syndrome: a study of 82 patients.

Neurologic involvement occurs in approximately 20% of patients with primary Sjögren syndrome (SS). However, the diagnosis of SS with neurologic involvement is sometimes difficult, and central nervous system (CNS) manifestations have been described rarely. We conducted the current study to describe the clinical and laboratory features of SS patients with neurologic manifestations and to report their clinical outcome. We retrospectively studied 82 patients (65 women and 17 men) with neurologic manifestations associated with primary SS, as defined by the 2002 American-European criteria. The mean age at neurologic onset was 53 years. Neurologic involvement frequently preceded the diagnosis of SS (81% of patients). Fifty-six patients had CNS disorders, which were mostly focal or multifocal. Twenty-nine patients had spinal cord involvement (acute myelopathy [n = 12], chronic myelopathy [n = 16], or motor neuron disease [n = 1]). Thirty-three patients had brain involvement and 13 patients had optic neuropathy. The disease mimicked relapsing-remitting multiple sclerosis (MS) in 10 patients and primary progressive MS in 13 patients. We also recorded diffuse CNS symptoms: some of the patients presented seizures (n = 7), cognitive dysfunction (n = 9), and encephalopathy (n = 2). Fifty-one patients had peripheral nervous system involvement (PNS). Symmetric axonal sensorimotor polyneuropathy with a predominance of sensory symptoms or pure sensory neuropathy occurred most frequently (n = 28), followed by cranial nerve involvement affecting trigeminal, facial, or cochlear nerves (n = 16). Multiple mononeuropathy (n = 7), myositis (n = 2), and polyradiculoneuropathy (n = 1) were also observed. Thirty percent of patients (all with CNS involvement) had oligoclonal bands. Visual evoked potentials were abnormal in 61% of the patients tested. Fifty-eight patients had magnetic resonance imaging (MRI) of the brain. Of these, 70% presented white matter lesions and 40% met the radiologic criteria for MS. Thirty-nine patients had a spinal cord MRI. Abnormalities were observed only in patients with spinal cord involvement. Among the 29 patients with myelopathy, 75% had T2-weighted hyperintensities. Patients with PNS manifestations had frequent extraglandular complications of SS. Anti-Ro/SSA or anti-La/SSB antibodies were detected in 21% of patients at the diagnosis of SS and in 43% of patients during the follow-up (mean follow-up, 10 yr). Biologic abnormalities were more frequently observed in patients with PNS involvement than in those with CNS involvement (p < 0.01). Fifty-two percent of patients had severe disability, and were more likely to have CNS involvement than PNS involvement (p < 0.001). Treatment by cyclophosphamide allowed a partial recovery or stabilization in patients with myelopathy (92%) or multiple mononeuropathy (100%). The current study underlines the diversity of neurologic complications of SS. The frequency of neurologic manifestations revealing SS and of negative biologic features, especially in the event of CNS involvement, could explain why SS is frequently misdiagnosed. Screening for SS should be systematically performed in cases of acute or chronic myelopathy, axonal sensorimotor neuropathy, or cranial nerve involvement. The outcome is frequently severe, especially in patients with CNS involvement. Our study also underlines the efficacy of cyclophosphamide in myelopathy and multiple neuropathy occurring during SS.

Adult↗
PubMed2004

Autoantibodies against alpha-fodrin in Sjögren's syndrome with neurological manifestations.

OBJECTIVE: To investigate the diagnostic value of autoantibodies against alpha-fodrin in patients with Sjögren's syndrome (SS) with neurological manifestations compared to SS patients without neurological manifestations, a control group, and patients with other neurological autoimmune diseases including systemic lupus erythematosus (SLE) with neurological manifestations and multiple sclerosis (MS). METHODS: We evaluated alpha-fodrin autoantibodies in 31 patients with SS with neurological manifestations, 53 SS patients without neurological symptoms, 38 patients with SLE, 60 with MS, and 160 controls. RESULTS: Twenty of the 31 SS patients with neurological manifestations (64.5%) had an increased concentration of IgA and/or IgG anti-alpha-fodrin. This was not statistically different from that of SS patients without neurological symptoms (73.6%), but was higher than the number with SSA/SSB antibodies, which were found in 15 (48%) of our SS patients without neurological manifestations. When the results of the 2 tests were combined, 28 of the 31 (90.3%) patients had positive autoantibodies (alpha-fodrin and/or SSA/SSB). Alpha-fodrin antibodies were increased in 8 (13.3%) of the 60 patients with MS, in 6 (15.7%) of 38 patients with SLE, and in 10 (6.3%) of 160 controls. CONCLUSION: Our results confirm that alpha-fodrin antibodies are an additional diagnostic tool for SS. This test is of particular interest for patients with SS with neurological manifestations, in whom anti SSA/SSB antibodies are less frequently found.

Adult↗
PubMed2003

Phrenic nerve palsy as a feature of chronic inflammatory demyelinating polyradiculoneuropathy.

We report four patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) who presented with phrenic nerve palsy, which was unilateral in two instances. The two patients with bilateral phrenic nerve involvement required mechanical ventilation. After treatment with intravenous immunoglobulins (i.v.Ig) or steroids, the sensorimotor deficit and respiratory parameters improved in three patients, but the fourth patient remained ventilator dependent and died from pulmonary infection. Although rare, phrenic nerve palsy may be a feature of CIDP and may be responsive to treatment with i.v.Ig or steroids.

Aged↗
PubMed2003

Multiple sclerosis and depression: influence of interferon beta therapy.

BACKGROUND AND OBJECTIVES: Depression is frequently part of the clinical picture of multiple sclerosis (MS). Major depression affects one in two patients with MS during the course of their lifetime. Our objectives were to determine first, whether interferon beta-1a (IFNbeta-1a) treatment increases the risk or level of depression and, secondly, whether depression status and depression evolution are related to the clinical characteristics of the disease. PATIENTS AND METHODS: We investigated 106 consecutive patients with relapsing remitting MS treated with IFNbeta-1a (Avonex). Patients with evidence of severe depression were excluded. The depression status, scored on the Beck Depression Inventory (BDI-II) (stratified as minimum, mild, moderate or severe level), and disability, scored on the Expanded Disability Status Scale (EDSS), were evaluated before and after 12 months of IFNbeta-1a treatment. RESULTS: At baseline, 85% of patients had a minimum or a mild depression status and after 12 months of treatment most of them (83%) retained their baseline status. Beck scores before and after treatment were not significantly different (P = 0.63). There was no correlation between age, gender, duration of illness or EDSS score and Beck score at baseline (P = 0.696). Patients with disability progression after one year of IFNbeta-1a treatment had a significantly higher Beck score at baseline than patients without disability progression (P = 0.003). CONCLUSION: IFNbeta-1a (Avonex) does not seem to significantly influence the depression status of MS patients even in those with disability progression.

Adjuvants, Immunologic↗
PubMedDate not supplied

Interleukin-10 promoter polymorphism in multiple sclerosis: association with disease progression.

Interleukin-10 (IL-10) is a potent anti-inflammatory and immunosuppressive cytokine that modulates disease expression in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). In previous studies, two dinucleotide repeat elements (microsatellites G and R) were identified, respectively located about 1.1 and 4.0 kb upstream of the IL-10 gene transcription initiation site. Several of their alleles were found to be associated with the level of IL-10 production. The aim of our study was to determine whether sequence variations in the IL-10 gene were associated with MS susceptibility and progression. To do so, we analyzed the distribution of IL-10.R and IL-10.G alleles and genotype polymorphisms in MS patients and healthy controls. We then correlated our findings with disease severity in MS patients using the progression index (PI). Patients were classified as experiencing mild (PI < 0.5) or severe (PI > 0.5) disease progression. Our results show no association between the IL-10.R microsatellite and MS, regardless of disease severity. However, IL-10.G microsatellite genotyping showed that IL-10.G9/9, G10/13, G11/13 and G13/14 were more frequently found in patients with mild disease progression (p = 0.005). We also found that in patients with severe disease progression, IL-10.G9/10, G9/11, G9/13 and G12/13 were over-represented (p = 0.002). Our study indicates that neither the IL-10.R or the IL-10.G alleles are associated with predisposition to MS. However, several IL-10.G genotypes might emerge as markers of disease progression.

Adolescent↗