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Biomedical subjects

E Nobile-Orazio

Publications and source records attributed to E Nobile-Orazio.

At least 19 recordsLinked to original sources
PubMed2006

Immunotherapy for IgM anti-myelin-associated glycoprotein paraprotein-associated peripheral neuropathies.

BACKGROUND: Serum monoclonal anti-myelin associated glycoprotein antibodies may be pathogenic in some people with IgM paraprotein and demyelinating neuropathy. Immunotherapies aimed at reducing the level of these antibodies might be expected to be beneficial. OBJECTIVES: To examine the efficacy of any form of immunotherapy in reducing disability and impairment resulting from IgM anti-myelin associated glycoprotein paraprotein-associated demyelinating peripheral neuropathy. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group Register (March 2005), MEDLINE (January 1966 to March 2005) and EMBASE (January 1980 to March 2005) for controlled trials. We also checked bibliographies and contacted authors and experts in the field. SELECTION CRITERIA: We included randomised or quasi-randomised controlled trials of participants of any age treated with any type of immunotherapy for anti-myelin-associated glycoprotein antibody associated demyelinating peripheral neuropathy with monoclonal gammopathy of undetermined significance of any severity. Our primary outcome measure was change in the Neuropathy Impairment Scale or Modified Rankin Scale at six months after randomisationSecondary outcome measures were: Neuropathy Impairment Scale or the Modified Rankin Score at 12 months after randomisation; ten-metre walk time, subjective clinical scores and electrophysiological parameters at six and 12 months after randomisation; IgM paraprotein levels and anti-myelin associated glycoprotein antibody titres at six months after randomisation and adverse effects of treatments. DATA COLLECTION AND ANALYSIS: We identified eight possible trials. Of these, five randomised controlled trials were included after discussion between the authors. One author extracted and the other checked the data. No missing data could be obtained from trial authors. MAIN RESULTS: The five eligible trials (97 participants) tested intravenous immunoglobulin, interferon-alpha or plasma exchange. Only two, of intravenous immunoglobulin, had comparable interventions and outcomes but both were short-term. There were no significant benefits of the treatments used in the outcomes predefined for this review, but not all the predefined outcomes were used in every included trial. Intravenous immunoglobulin showed benefits in terms of improvement in Modified Rankin Scale at two weeks and 10-metre walk time at four weeks. Serious adverse effects of intravenous immunoglobulin are known to occur from observational studies but none were encountered in these trials. AUTHORS' CONCLUSIONS: There is inadequate reliable evidence from trials of immunotherapies in anti-myelin associated glycoprotein paraproteinaemic neuropathy to recommend any particular immunotherapy treatment. Intravenous immunoglobulin is relatively safe and may produce some short-term benefit. Large well-designed randomised trials of at least six to 12 months duration are required to assess existing or novel therapies.

Demyelinating Diseases↗
PubMed2006

European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society.

Numerous sets of diagnostic criteria have sought to define chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and randomized trials and systematic reviews of treatment have been published. The objective is to prepare consensus guidelines on the definition, investigation and treatment of CIDP. Disease experts and a patient representative considered references retrieved from MEDLINE and Cochrane Systematic Reviews in May 2004 and prepared statements which were agreed in an iterative fashion. The Task Force agreed on good practice points to define clinical and electrophysiological diagnostic criteria for CIDP with or without concomitant diseases and investigations to be considered. The principal treatment recommendations were: (1) intravenous immunoglobulin (IVIg) or corticosteroids should be considered in sensory and motor CIDP (level B recommendation); (2) IVIg should be considered as the initial treatment in pure motor CIDP (Good Practice Point); (3) if IVIg and corticosteroids are ineffective plasma exchange (PE) should be considered (level A recommendation); (4) If the response is inadequate or the maintenance doses of the initial treatment are high, combination treatments or adding an immunosuppressant or immunomodulatory drug should be considered (Good Practice Point); (5) Symptomatic treatment and multidisciplinary management should be considered (Good Practice Point).

Humans↗
PubMed2006

European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of multifocal motor neuropathy.

Several diagnostic criteria for multifocal motor neuropathy have been proposed in recent years and a beneficial effect of intravenous immunoglobulin (IVIg) and various other immunomodulatory drugs has been suggested in several trials and uncontrolled studies. The objectives were to prepare consensus guidelines on the definition, investigation and treatment of multifocal motor neuropathy. Disease experts and a patient representative considered references retrieved from MEDLINE and the Cochrane Library in July 2004 and prepared statements which were agreed in an iterative fashion. The Task Force agreed good practice points to define clinical and electrophysiological diagnostic criteria for multifocal motor neuropathy and investigations to be considered. The principal recommendations and good practice points were: (i) IVIg (2 g/kg given over 2-5 days) should be considered as the first line treatment (level A recommendation) when disability is sufficiently severe to warrant treatment. (ii) Corticosteroids are not recommended (good practice point). (iii) If initial treatment with IVIg is effective, repeated IVIg treatment should be considered (level C recommendation). The frequency of IVIg maintenance therapy should be guided by the individual response (good practice point). Typical treatment regimens are 1 g/kg every 2-4 weeks or 2 g/kg every 4-8 weeks (good practice point). (iv) If IVIg is not or not sufficiently effective then immunosuppressive treatment may be considered. Cyclophosphamide, ciclosporin, azathioprine, interferon beta1a, or rituximab are possible agents (good practice point). (v) Toxicity makes cyclophosphamide a less desirable option (good practice point).

Advisory Committees↗
PubMed2006

European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of paraproteinaemic demyelinating neuropathies: report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society.

BACKGROUND: Paraprotein-associated neuropathies have heterogeneous clinical, neurophysiological, neuropathological and haematological features. Objectives. To prepare evidence-based and consensus guidelines on the clinical management of patients with both a demyelinating neuropathy and a paraprotein (paraproteinaemic demyelinating neuropathy, PDN). METHODS: Search of MEDLINE and the Cochrane library, review of evidence and consensus agreement of an expert panel. RECOMMENDATIONS: In the absence of adequate data, evidence based recommendations were not possible but the panel agreed the following good practice points: (1) Patients with PDN should be investigated for a malignant plasma cell dyscrasia. (2) The paraprotein is more likely to be causing the neuropathy if the paraprotein is immunoglobulin (Ig)M, antibodies are present in serum or on biopsy, or the clinical phenotype is chronic distal sensory neuropathy. (3) Patients with IgM PDN usually have predominantly distal and sensory impairment, with prolonged distal motor latencies, and often anti-myelin associated glycoprotein antibodies. (4) IgM PDN sometimes responds to immune therapies. Their potential benefit should be balanced against their possible side-effects and the usually slow disease progression. (5) IgG and IgA PDN may be indistinguishable from chronic inflammatory demyelinating polyradiculoneuropathy, clinically, electrophysiologically, and in response to treatment. (6) For POEMS syndrome, local irradiation or resection of an isolated plasmacytoma, or melphalan with or without corticosteroids, should be considered, with haemato-oncology advice.

Advisory Committees↗
PubMed2005

Long term disability and social status change after Guillain-Barré syndrome.

OBJECTIVE: Even if the majority of patients with Guillain-Barré syndrome (GBS) have a favourable functional outcome some residual motor and sensory signs and symptoms may remain. The aim of this study was to evaluate the long-term effect of GBS on daily life,working activities, hobbies and social status and the presence of residual symptoms. PATIENTS AND METHODS: Seventy patients with GBS enrolled in a case-control study were examined. Information on signs or symptoms during the acute phase of the disease was retrieved from medical records and an ad-hoc questionnaire administered during hospitalization. Patients were interviewed by phone 3 to 5 years after disease onset about residual symptoms and changes in daily living. Disability and handicap were assessed using the Hughes, Rankin and Rotterdam 9-items scale. RESULTS: At follow-up 45 patients (64 %) made a complete functional recovery; 19 patients (27%) had some minor limitations in daily life although they were able to perform all their activities independently while 6 (9 %) needed aid for some hours or continuously during the day. Nineteen patients (27 %) had, however, to make substantial changes in their job, hobbies or social activities. There was no significant correlation between clinical and laboratory features during the acute phase of GBS and outcome. CONCLUSIONS: Although over 90% of our GBS patients had a more or less complete functional recovery, almost 30% of them had to make substantial changes in daily life. These findings indicate that GBS still has a significant impact on patients' life which may go beyond their residual disability or impairment. Treatment of GBS should not be only aimed at improving patients' disability but also at limiting the impact of the disease on their social life.

Adult↗
PubMed2005

Immunosuppressant and immunomodulatory treatments for multifocal motor neuropathy.

BACKGROUND: Multifocal motor neuropathy is a distinct clinical entity characterised by progressive, predominantly distal, asymmetrical limb weakness and minimal sensory abnormality. The diagnostic feature of this condition is the presence of multiple partial motor nerve conduction blocks. Controlled trials have demonstrated the efficacy of regular intravenous immunoglobulin infusions. Immunosuppressive agents have been used as primary, second-line or adjunctive agents for its treatment. This review was undertaken to identify and review systematically randomised controlled trials of immunosuppressive agents. The use of intravenous immunoglobulin will be the subject of a separate review. OBJECTIVES: To provide the best available evidence from randomised controlled trials on the role of immunosuppressive agents for the treatment of multifocal motor neuropathy. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group trials register for all trials of multifocal motor neuropathy published, using 'multifocal motor neuropathy' OR 'chronic inflammatory demyelinating polyradiculoneuropathy' OR ' conduction block' OR ' motor neuropathy' AND 'immunosuppressive agents', 'immunosuppressants', 'corticosteroids', 'plasma exchange', 'azathioprine', 'cyclophosphamide', 'cyclosporin', 'ciclosporin', 'methotrexate', and 'mycophenolate', 'immunomodulatory agents', 'interferon', 'total lymphoid irradiation' or 'bone marrow transplantation' as search terms. In addition we searched MEDLINE, EMBASE for 2000 and 2001 and CINAHL, LILACS for all years. We updated the register search in February 2004 and searched MEDLINE (January 1966 to end May 2004) and EMBASE (January 1980 to end May 2004). SELECTION CRITERIA: All randomised controlled trials and quasi-randomised clinical trials in which allocation was not random but was intended to be unbiased (e.g. alternate allocation) were to have been selected. Since no such trials were discovered, all prospective and retrospective case series were included in the 'background' or 'discussion' sections of the review. DATA COLLECTION AND ANALYSIS: All studies on multifocal motor neuropathy or lower motor neuron weakness with conduction block and no sensory abnormality were scrutinised for data on patients treated with any form of immunosuppressive agents besides intravenous immunoglobulin. The information on the outcome of treatment was then collated and summarised. MAIN RESULTS: We found no randomised controlled trials of any immunosuppressive agents for multifocal motor neuropathy. We summarised the results of retrospective and prospective case series in the discussion of the review. AUTHORS' CONCLUSIONS: There are no randomised controlled trials to indicate whether immunosuppressive agents are beneficial in multifocal motor neuropathy.

Humans↗
PubMed2004

How long is IVIg effective in multifocal motor neuropathy?

The authors treated 10 patients with multifocal motor neuropathy (MMN) responding to an initial course of IV immunoglobulin (IVIg) with periodic infusion for 5 to 12 years (mean 8.2 years). At last follow-up, only two patients had maintained the maximal improvement achieved during therapy while eight worsened despite increasing Ig dosage. This decline started after 3 to 7 years (mean 4.8 years) of therapy and correlated with a reduction of distal compound muscle action potential amplitudes (p < 0.019). The effectiveness of IVIg in MMN often declines after several years possibly associated with the development of axonal degeneration.

Adult↗
PubMed2003

Immunotherapy for IgM anti-Myelin-Associated Glycoprotein paraprotein-associated peripheral neuropathies.

BACKGROUND: Serum monoclonal anti-Myelin Associated Glycoprotein antibodies may be pathogenic in some patients with IgM paraprotein and demyelinating neuropathy. Immunotherapies aimed at reducing the level of these antibodies might be expected to be of benefit in the treatment of the neuropathy. Many potential therapies have been described in small trials, uncontrolled studies and case reports. OBJECTIVES: To examine the efficacy of any form of immunotherapy in reducing disability and impairment resulting from IgM anti-Myelin Associated Glycoprotein paraprotein-associated demyelinating peripheral neuropathy. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group register (August 2002) and MEDLINE (January 1966 - August 2002) and EMBASE (January 1980 - August 2002) for controlled trials, checked the bibliographies to identify other controlled trials and contacted authors and other experts in the field. SELECTION CRITERIA: Types of studies: randomised or quasi-randomised controlled trials. TYPES OF PARTICIPANTS: patients of any age with anti-Myelin Associated Glycoprotein antibody associated demyelinating peripheral neuropathy with monoclonal gammopathy of undetermined significance of any severity. Types of interventions: any type of immunotherapy. Types of outcome measures: Primary: improvement in the Neuropathy Disability Score or Modified Rankin Scale six months after randomisation Secondary: Neuropathy Disability Score and/or the Modified Rankin Score 12 months after randomisation. Ten metre walk time, subjective clinical scores and electrophysiological parameters at six and 12 months after randomisation. IgM paraprotein levels and anti-Myelin Associated Glycoprotein antibody titres six months after randomisation. Adverse effects of treatments. DATA COLLECTION AND ANALYSIS: We identified six randomised controlled trials of which five were included after discussion between the authors. One author extracted the data and the other checked them. No missing data could be obtained from authors. MAIN RESULTS: The five eligible trials used four of the many available immunotherapy treatments. Only two had comparable interventions and outcomes but these were only short-term studies. There were no significant benefits of the treatments used in the predefined outcomes. However intravenous immunoglobulin showed benefits in terms of improved Modified Rankin Scale at two weeks and 10 metre walk time at four weeks. Serious adverse effects of intravenous immunoglobulin are known to occur from observational studies but none were encountered in these trials. REVIEWER'S CONCLUSIONS: There is inadequate reliable evidence from trials of immunotherapies in anti-Myelin Associated Glycoprotein paraproteinaemic neuropathy to recommend any particular immunotherapy treatment. Intravenous immunoglobulin is relatively safe and may produce some short-term benefit. Large well designed randomised trials are required to assess the efficacy of promising new therapies.

Demyelinating Diseases↗
PubMed2003

Treatment of multifocal motor neuropathy.

Multifocal motor neuropathy (MMN) is a purely motor multineuropathy characterized by multifocal conduction blocks on motor nerves. The pathogenesis of MMN is not known but its frequent association with anti-ganglioside antibodies and the improvement after immune therapies support an immune pathogenesis. Patients with MMN do not respond to steroids or plasma exchange, which may occasionally even worsen the symptoms, while the efficacy of other immune suppressive therapies is controversial. More than 80% of MMN patients rapidly and consistently improve with highdose intravenous immunoglobulin (IVIg), the efficacy of which has been confirmed in four controlled studies. In most patients, however, the effects of this therapy only last a few weeks and improvement has to be maintained with periodic infusions for long periods of time, if not indefinitely.

Autoantibodies↗
PubMed2002

Immunosuppressive treatment for multifocal motor neuropathy.

BACKGROUND: Multifocal motor neuropathy is a distinct clinical entity characterised by progressive, predominantly distal, asymmetrical limb weakness and minimal sensory abnormality. The pathognomonic feature of this condition is the presence of multiple partial motor nerve conduction blocks. Controlled trials have demonstrated the efficacy of regular intravenous immunoglobulin infusions. Immunosuppressive agents have been used as primary, second-line or adjunctive agents for its treatment. This review was undertaken to identify and review systematically randomised controlled trials of immunosuppressive agents. The use of intravenous immunoglobulin will be the subject of a separate review. OBJECTIVES: To provide the best available evidence from randomised controlled trials on the role of immunosuppressive agents for the treatment of multifocal motor neuropathy. SEARCH STRATEGY: The Cochrane Neuromuscular Disease Group register was searched for all trials of multifocal motor neuropathy published, using 'multifocal motor neuropathy' OR 'chronic inflammatory demyelinating polyradiculoneuropathy' OR ' conduction block' OR ' motor neuropathy' AND 'immunosuppressive agents', 'immunosuppressants', 'corticosteroids', 'plasma exchange', 'azathioprine', 'cyclophosphamide', 'cyclosporin', 'methotrexate', and 'mycophenolate', 'immunomodulatory agents', 'interferon', 'total lymphoid irradiation' or 'bone marrow transplantation' as search terms. In addition we searched MEDLINE, EMBASE for 2000 and 2001 and CINAHL, LILACS for all years. SELECTION CRITERIA: All randomised controlled trials and quasi-randomised clinical trials in which allocation was not random but was intended to be unbiased (e.g. alternate allocation) were to have been selected. Since no such trials were discovered, all prospective and retrospective case series were included in 'background' or 'discussion' sections of the review. DATA COLLECTION AND ANALYSIS: All studies on multifocal motor neuropathy or lower motor neuron weakness with conduction block and no sensory abnormality were scrutinized for data on patients treated with any form of immunosuppressive agents besides intravenous immunoglobulin. The information on the outcome of treatment was then collated and summarised. MAIN RESULTS: We found no randomised controlled trials of any immunosuppressive agents for multifocal motor neuropathy. We summarised the results of retrospective and prospective case series in the discussion of the review. REVIEWER'S CONCLUSIONS: There are no randomised controlled trials to indicate whether immunosuppressive agents are beneficial in multifocal motor neuropathy.

Humans↗
PubMed2002

Distinctive abnormalities of motor axonal strength-duration properties in multifocal motor neuropathy and in motor neurone disease.

The strength-duration function is a classic measure of neural excitability. When studied on peripheral motor axons it reflects the intrinsic nodal membrane properties, and its time-constant (tau(SD) or chronaxie) predominantly depends on non-voltage-gated, rest Na(+) inward conductances. We assessed the strength-duration curve of ulnar motor axons in 22 nerves of healthy controls, in 18 nerves of patients with multifocal motor neuropathy with conduction blocks (MMN), and in 19 nerves of patients with motor neurone disease (MND). The compound muscle action potential (CMAP) was smaller in nerves of both groups of patients than in controls (P < 0.05). The rheobasic current (rh(50%)) [mean +/- standard deviation (SD)] was higher in patients with MMN than in controls (13.3 +/- 16.3 mA; controls 4.7 +/- 1.7 mA, P < 0.05). The tau(SD) was differentially abnormal in the nerves of the two groups of patients: it was prolonged in the nerves of patients with MND for >or=40 years (227.2 +/- 34.5 micro s; controls 190.9 +/- 51.0 micro s, P < 0.05), but it was shortened in the nerves of patients with MMN (146.5 +/- 55.4 micro s; controls 208.6 +/- 51.2 micro s, P < 0.05) who had not been treated recently with high-dose intravenous immunoglobulin (IVIg). Nerves of patients with recently treated MMN (<6 weeks) who were under the therapeutic effect of IVIg had a normal tau(SD)(.) Our results suggest that, probably due to an immuno-mediated rest Na(+) channel dysfunction, Na(+) conductances are reduced in MMN. This abnormality is a function of the time after the last IVIg treatment and involves also the axonal membrane outside the conduction block. Conversely, in MND, possibly owing to the ionic leakage of degenerating membrane, rest Na(+) conductances are increased. Measuring the strength-duration curve of the ulnar motor axons might be useful in the differential diagnosis between de novo MMN and MND.

Action Potentials↗
PubMed2002

Multifocal motor neuropathy: clinical and immunological features and response to IVIg in relation to the presence and degree of motor conduction block.

OBJECTIVE: To determine whether patients with clinically typical multifocal motor neuropathy (MMN) with or without definite or probable conduction block (CB) differ in terms of clinical presentation, immunological findings, or response to treatment with intravenous immunoglobulin (IVIg). METHODS: 23 consecutive patients were studied with the typical clinical features of MMN, consisting of a progressive multineuropathic motor impairment with minimal or no sensory loss. In 14 patients, electrophysiological studies disclosed the presence of a definite or probable CB according to the criteria proposed by the American Association of Electrodiagnostic Medicine (AAEM) in at least one motor nerve. Six patients had possible CB, defined as a degree of CB 10% less than that required by the AAEM for probable CB, while no CB was detected in three patients. RESULTS: Patients with possible CB did not differ from those with a definite or probable CB in terms of age at disease onset (mean 38.8 v 38.2 years, respectively), distribution and severity of limb weakness, clinical impairment (mean Rankin score 2.2 in both), and frequency of antiganglioside antibodies (33% v 29%). Patients with possible CB had a longer mean disease duration (9 v 5.9 years, p < 0.05) and a less frequent consistent response to IVIg (67% v 86%) than those with a definite or probable CB. Patients without a detectable CB had a similar frequency of antiganglioside antibodies (33%) but had a longer disease duration (20.3 years), greater impairment (Rankin score 2.7), and more frequent signs of axonal degeneration (41% of examined motor nerves) than patients with CB (13-15%, p < 0.005). Only one patient without detectable CB (33%) consistently improved with IVIg. CONCLUSIONS: Patients with possible CB were clinically and immunologically indistinguishable from those with definite or probable CB, albeit with a slightly less frequent response to IVIg. This finding suggests that failure to fulfil AAEM criteria for CB in patients with otherwise clinically typical MMN should not preclude this diagnosis and consequently a treatment trial with IVIg. Whether the longer duration and greater severity of the disease and more frequent axonal impairment in patients without detectable CB than in those with CB explain their lower response to IVIg remains to be established.

Adult↗
PubMed2002

Neuropathies associated with IgG and IgA monoclonal gammopathy.

Neuropathy has been frequently reported in patients with monoclonal gammopathy, particularly those with monoclonal gammopathy of undetermined significance (MGUS). While the neuropathy associated with IgM-MGUS is well characterized and is often associated with a reactivity of the monoclonal protein with neural antigens, the relationship between the neuropathy and IgG and IgA MGUS is less clear. We review here the clinical, electrophysiological and pathogenetic features of neuropathies associated with IgG and IgA M-proteins in order to determine whether they represent distinct clinical entities and, most importantly, whether the finding of an IgG or IgA monoclonal gammopathy in a patient with neuropathy should led to different diagnostic or therapeutical approaches. This review will mainly focus on neuropathies associated with MGUS since the disclosure of a malignant monoclonal gammopathy, including multiple or osteosclerotic myeloma, lymphoma or primary amyloidosis, in a patient with neuropathy usually divert the therapeutical decisions to the hematologist for an appropriate therapy of the underlying life threatening condition.

Humans↗
PubMed2001

Multifocal motor neuropathy.

Multifocal motor neuropathy (MMN) is a recently identified peripheral nerve disorder characterized by progressive, predominantly distal, asymmetric limb weakness mostly affecting upper limbs, minimal or no sensory impairment, and by the presence on nerve conduction studies of multifocal persistent partial conduction blocks on motor but not sensory nerves. The etiopathogenesis of MMN is not known, but there is some evidence, based mostly on the clinical improvement after immunological therapies, that the disease has an immunological basis. Antibodies, mostly IgM, to the gangliosides GM1, and though less frequently, GM2 and GD1a, are frequently detected in patients' sera, helping in the diagnosis of this disease. Even if there is some experimental evidence that these antibodies may be pathogenic in vitro, their role in the neuropathy remains to be established. Patients with MMN do not usually respond to steroids or plasma exchange, which may occasionally worsen the symptoms, while the efficacy of cyclophosphamide is limited by its relevant side effects. More than 80% of MMN patients rapidly improve with high dose intravenous immunoglobulin therapy (IVIg). The effect of this therapy is, however, transient and improvement has to be maintained with periodic infusions. A positive response to interferon-beta has been recently reported in a minority of patients, some of whom were resistant to IVIg. Even if many progresses have been made on the diagnosis and therapy of MMN, there are still several issues on the nosological position, etiopathogenesis and long-term treatment of this neuropathy that need to be clarified.

Autoantibodies↗
PubMed2001

Anti-GM(2) IgM antibody-induced complement-mediated cytotoxicity in patients with dysimmune neuropathies.

Anti-GM2 IgM antibodies have been reported in some patients with dysimmune neuropathy or lower motor neuron syndrome. To determine whether these antibodies can induce complement-dependent cytolysis we performed a cytotoxicity assay on neuroblastoma cells with sera from seven patients with demyelinating dysimmune neuropathies and high titers of anti-GM2 IgM. As controls we used sera from seven patients with other anti-neural reactivities, six with the same neuropathies but no anti-GM2 or other anti-neural reactivity and from eight normal subjects. Of the seven positive sera tested, six induced complement-mediated cytotoxicity, while none of the controls had any relevant effect on neuroblastoma cells. Preincubation of positive sera with purified GM2 removed cytotoxic activity. Affinity purified anti-GM2 IgM had the same cytotoxic anti-GM2 effect of whole serum while serum or complement alone did not have any effect. In four anti-GM2-positive patients the percentage of cell lysis correlated with anti-GM2 titers and with IgM staining of neuroblastoma cells while in two the cytotoxic effect was higher than expected from antibody titers. Complement-mediated cell lysis induced by anti-GM2 IgM antibodies may be a possible mechanism of neural damage in patients with dysimmune neuropathy and high titers of anti-GM2 IgM antibodies.

Chromatography, Affinity↗
PubMed2001

Combined pre- and postsynaptic action of IgG antibodies in Miller Fisher syndrome.

BACKGROUND: Miller Fisher syndrome (MFS), a variant of the Guillain-Barré syndrome, is associated with the presence of neuromuscular blocking antibodies, some of which may be directed at the ganglioside GQ1b. MATERIALS AND METHODS: The authors investigated the in vitro effects of serum and purified immunoglobulin (Ig) G in a total of 11 patients with typical MFS during active disease, and in three of those patients after recovery. From one patient's serum, we prepared an IgG fraction enriched in anti-GQ1b antibodies by affinity chromatography. For combined pre- and postsynaptic analysis, endplate currents were recorded by a perfused macro-patch clamp electrode. Postsynaptic nicotinic acetylcholine receptor channels were investigated by an outside-out patch clamp technique in cultured mouse myotubes. RESULTS: AllMFS-sera depressed evoked quantal release and reduced the amplitude of postsynaptic currents. Five of the 11 sera were additionally examined by outside-out patch clamp analysis and caused a concentration-dependent and reversible decrease in acetylcholine-induced currents. The time course of activation and desensitization of nicotinic acetylcholine receptor channels was not altered by MFS-IgG. Nine patients (82 %) were positive for anti-GQ1b antibodies in ELISA and dot-blot. The enriched anti-GQ1b antibody fraction had a similar effect as whole serum. After recovery from MFS, blocking activity was lost and sera originally positive for anti-GQ1b antibodies became negative. CONCLUSION: Circulating IgG antibodies induce both pre- and postsynaptic blockade and may play a pathogenic role in acute MFS.

Acetylcholine↗