Immunoglobulin G subclasses are normal in motor neuron disease.
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Humans↗
Biomedical subjects
J Veitch
Publications and source records attributed to J Veitch.
Immunoglobulin subclass distribution and binding characteristics of anti-GQ1b antibodies in Miller Fisher syndrome.
Circulating IgG antibodies to carbohydrate determinants on GQ1b ganglioside are found in the acute phase sera of patients with Miller Fisher syndrome, a variant of Guillain-Barré syndrome. Here we report that the IgG subclass distribution of the anti-GQ1b antibodies is mainly restricted to IgG1 and IgG3 antibodies, subclasses typically associated with a T cell-dependent immune response to protein antigens. This is highly unusual in that IgG responses to carbohydrate determinants are typically of the IgG2 subclass. Anti-GQ1b antibodies also have a limited ability to bind GQ1b in a membrane-like environment, particularly at body temperature. These data suggest that the antigen initiating the immune response in MFS is not likely GQ1b but an unidentified cross-reactive glycoprotein antigen(s). Similar results were obtained for anti-GM1 IgG antibodies in Guillain-Barré syndrome.
Antibodies↗
Monoclonal IgM cold agglutinins with anti-Pr1d specificity in a patient with peripheral neuropathy.
A patient with a demyelinating sensory motor polyneuropathy secondary to IgM paraproteinaemia is reported. The paraprotein binds to the gangliosides GD1b, GT1b, GQ1b and GD3, all of which contain disialosyl groups with the sequence NeuAc alpha 2-8NeuAc alpha 2-3Gal. The paraprotein also acts as a cold agglutinin recognising the sialic-acid-dependent Pr1d antigenic determinant of the red cell membrane glycophorins. In this and in similar cases that have been reported, the coexistence of anti-Pr cold agglutinins and peripheral neuropathy suggest that they might be the causative agents of the disease.
Agglutinins↗
Acute ataxic neuropathy with cross-reactive antibodies to GD1b and GD3 gangliosides.
We report a patient with an acute, self-limiting neuropathy consisting of ataxia and areflexia, but without ophthalmoplegia or limb weakness, with transient, high-titer serum IgG antibodies to a single NeuAc(alpha 2-8)NeuAc-linked disialosyl epitope, as found on GD1b and GD3 gangliosides. The serum did not react with GQ1b, GT1a, or GT1b. This atypical case, which most closely represents an incomplete Miller Fisher syndrome, indicates that anti-GD1b/GD3 antibodies may be able to induce sensory ataxia.
Adult↗
Just what the doctor ordered.
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Consumer Advocacy↗
Antiglycolipid antibodies, immunoglobulins and paraproteins in motor neuron disease: a population based case-control study.
The role of humoral autoimmune factors in the pathogenesis of motor neuron disease (MND) is currently under considerable scrutiny. In particular, there have been many reports of abnormal serum immunoglobulin patterns and elevated titres of anti-ganglioside antibodies in patients with MND. However, many of these studies may be biased by the selection criteria for patients and controls. In order to carefully address this issue we obtained 82 blood samples from consecutive MND patients identified through a national MND register in combination with 82 community controls matched for age, sex and geographical area. We used these samples to determine the frequency of monoclonal immunoglobulins (mIgs) and measure the levels of serum immunoglobulins and anti-GM1 ganglioside antibodies in sporadic cases of MND in comparison with normal controls. Serum mIgs detected using high resolution and immunofixation agarose electrophoresis were present in 1.2% of MND patients and 2.4% of controls. Using a highly sensitive isoelectric focusing and immunoblotting method, monoclonal or oligoclonal immunoglobulins were found in 28% of MND patients and 27% of controls. Anti-GM1 antibodies were present in 26% of MND patients and 18% of controls (odds ratio = 1.5, 95%, CI 0.7-3.6) with no significant differences in titres between the 2 groups. Mean immunoglobulin G, A and M levels were equal in 2 groups. Thus, although alterations in these parameters were identified, we were unable to demonstrate any significant difference between MND patients and controls. We conclude that the majority of sporadic cases of MND are unlikely to have an autoimmune basis as judged by the lack of abnormalities in these parameters.
Adult↗
Peripheral neuropathy associated with monoclonal IgM anti-Pr2 cold agglutinins.
A patient with a chronic, large fibre sensory neuropathy had an immunoglobulin M lambda monoclonal paraprotein reactive at titres in excess of 1/10(5) with NeuNAc(alpha 2-8)NeuNAc(alpha 2-3)Gal configured disialosyl groups present on the gangliosides GD1b, GT1b, GQ1b, and GD3. The paraprotein showed weaker reactivity with GD1a, GM3, and LM1 but no reactivity with GM2, GM1, or asialo-GM1. In addition, the paraprotein had cold agglutinating activity with anti-Pr2 specificity, Pr2 being an antigenic determinant on membrane glycoproteins or glycolipids in erythrocytes or both. A large fibre sensory neuropathy with monoclonal anti-disialosyl antibodies is an increasingly recognised form of paraproteinaemic neuropathy.
Agglutinins↗
Miller Fisher syndrome is associated with serum antibodies to GQ1b ganglioside.
A recent report described serum anti-GQ1b ganglioside antibodies in Miller Fisher syndrome (MFS), a clinical variant of Guillain-Barré syndrome (GBS). Four consecutive cases of MFS all had high titre anti-GQ1b antibodies which were absent from all control sera including those of patients with GBS.
Autoantibodies↗
Motor-evoked responses in primary lateral sclerosis.
Primary lateral sclerosis (PLS) may be distinguished on the basis of clinical and pathological features from amyotrophic lateral sclerosis (ALS). The former is featured by a much longer clinical course, exclusively upper motor neuron findings, losses of precentral pyramidal neurons, and preservation of anterior horn cells. Electrophysiological studies of 7 PLS cases have shown normal peripheral motor conduction, absent or very delayed motor-evoked potentials, the occasional late development of denervation activity in distal muscles, and normal somatosensory-evoked potentials.
Aged↗
The relative roles of C4A and C4B in prevention of immune precipitation, solubilisation and immune adherence.
C4A and C4B levels were measured in serum from 246 normal individuals. Complement-mediated solubilisation, assayed using alkaline phosphatase anti-alkaline phosphatase immune complexes (IC), correlated with both C4A and C4B levels. However, C4A and C4B levels showed no correlation with solubilisation of bovine serum albumin (BSA) ICs, or with the prevention of immune precipitation of BSA or alkaline phosphatase ICs, nor with immune adherence assayed using thyroglobulin and BSA ICs.
Antigen-Antibody Complex↗
Measurement of complement activation products in patients with chronic rheumatic diseases.
Measurement of the complement activation products C1s:C1-inh, C3bP and C5b-9 by ELISA in plasma samples from normals, rheumatoid arthritis (RA) and systemic lupus erythematosis (SLE) patients showed significantly elevated levels in the two patient groups (P less than 0.0001 for C1s:C1-inh, C3bP and C5b-9) compared to normals. In seropositive RA patients there were significant correlations between the levels of the three complement activation complexes and IgM-RF, IgG-RF and IgA-RF. However, IgM-RF did not interfere with any of the ELISA systems. Mean levels of C1s:C1-inh, C3bP and C5b-9 were the same in paired plasma and synovial fluids; however, C3bP levels in the paired samples did not correlate with one another by rank. Our conclusions are that: (a) elevated plasma levels of these complement activation products are detectable in rheumatic diseases; (b) plasma levels of these complement activation products are related to Rheumatoid factor (RF) levels in seropositive RA patients; and (c) IgM-RF does not influence these solid-phase ELISA procedures.
Antibodies↗
Mechanism of action of an inhibitor of complement-mediated prevention of immune precipitation.
Glycoprotein 60 (gp60) is a normal plasma protein (mean concentration in normal serum 34 micrograms/ml) that is present in increased levels (mean concentration 97 micrograms/ml) in the sera of patients with rheumatoid arthritis (RA). Purified gp60 binds to IgG but not to IgM, and competitively inhibits the binding of C1q. In fluid-phase studies, purified gp60 was shown to reduce immune complex-mediated complement activation in a dose-dependent manner. The addition of Fab anti-gp60 to normal serum was associated with (i) increased levels of complement-mediated prevention of immune precipitation (PIP); (ii) increased total haemolytic complement activity when EAIgG, but not when EAIgM, were used as targets; and (iii) increased immune complex-mediated complement activation. Thus gp60 appears to regulate immune complex-mediated classical pathway activation. The findings that Fab anti-gp60 (i) only partly restored PIP in RA sera showing reduced PIP levels and (ii) only partly reduced inhibition of PIP by RA sera, show that gp60 is not entirely responsible for these abnormalities.
Antigen-Antibody Complex↗
Failure to detect antideoxyribonucleic acid antibody in Graves' disease in Caucasians.
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Antibodies, Antinuclear↗
Familial properdin deficiency associated with chronic discoid lupus erythematosus.
A large family comprised of 18 members is described. Four male members are properdin-deficient, all are healthy bar the index patient who presented with chronic discoid lupus erythematosus. Serum from properdin-deficient males had a reduced ability to lyse rabbit erythrocytes via the alternative pathway or solubilize pre-formed immune complexes. Addition of purified properdin restored these activities. Classical pathway activity was normal. Definite, probable and possible female carriers had normal classical and alternative pathway activities.
Family↗
Quantitation of human C4A and C4B, in serum and plasma by enzyme-linked immunoadsorbent assay.
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Alleles↗
Behavioral and neurochemical profile of the spontaneously diabetic Wistar BB rat.
The overall objective of the present investigation was to examine the behavioral and neurochemical profile of long-term diabetes (2-4 months), in the spontaneously diabetic Wistar BB rat (SDR). This animal model mimics the salient symptomatology of Type-I diabetes in man and circumvents confounds attributed to non-specific effects encountered in the chemically-induced models of diabetes. The first set of experiments were designed to investigate the effects of dopamine (DA) agonists and circadian cycle on the following spontaneous behaviors: locomotion, floor activity, rearing frequency and rearing duration. The results demonstrated that the SDR manifests (1) a blunted response to D-amphetamine (0.5-3.0 mg/kg; i.p.), and (2) lower levels of spontaneous locomotor and rearing activity in the latter part of the dark cycle, particularly at the transition of the cycle from dark to light. The next set of experiments assessed the status of brain catecholamine and metabolite levels in the insulin maintained and deprived SDR. The regional catecholamine and metabolite levels of the insulin-maintained SDR were not significantly different from those of the non-diabetic or the genetically distinct controls. However, the cessation of insulin administration to the SDR for 4 days resulted in significant increases in the levels of norepinephrine in the cortex and the hypothalamus, DA in the hippocampus, and homovanillic acid in the striatum.
Animals↗
An inhibitor of complement-mediated prevention of immune precipitation in rheumatoid arthritis--relationship to disease activity and systemic manifestations.
In normal serum complement prevents precipitation of antigen-antibody complexes (PIP). However rheumatoid arthritis (RA) serum contains an inhibitor of this complement-mediated function. We have undertaken two prospective studies in order to look for any relationship between the presence and levels of inhibitory activity in sera and synovial fluids (SF) of patients with RA and disease activity (study A), and the presence of systemic manifestations (nodules and vasculitis) of RA (study B). In study A, levels of inhibitory activity were highest in the sera and synovial fluids of patients with seropositive RA. However there was no correlation between the inhibitory levels and indices of generalised disease activity (articular index, erythrocyte sedimentation rate (ESR), haemoglobin, white cell and platelet counts). Local joint tenderness score correlated weakly with the inhibitory level in SF (P less than 0.05). There was no correlation, however, with either the SF protein concentration or white cell count. In study B, PIP was shown to be lower in patients with the systemic manifestations of RA than in those with purely articular manifestations. PIP was particularly low in those patients with vasculitis compared to those with subcutaneous nodules. Serum levels of inhibitory activity were highest in patients with vasculitis and lowest in those with articular disease only, whereas patients with nodules had intermediate levels. Our conclusion is that inhibition of immune precipitation is not associated with disease activity, but is associated with the extra-articular manifestations of RA. The inhibitory factor may play a role in the pathogenesis of RA.
Antigen-Antibody Complex↗
Inhibition of complement-mediated solubilisation of antigen-antibody complexes by serum factor(s) in patients with various connective tissue diseases.
Control of immune complex formation is important to limit disease resulting from their deposition in tissues. Any inhibition of immune complex solubilisation is thus significant in the pathogenesis of immune complex diseases. More than half of our patients with various rheumatic connective tissue diseases were demonstrated to have serum inhibition of immune complex solubilisation (12/16 rheumatoid arthritis, 22/37 systemic lupus erythematosus, 16/29 primary Sjogren's syndrome, and eight of nine with mixed connective tissue disease). This serum inhibitory activity did not correlate well with serum levels of IgM rheumatoid factor or circulating immune complexes, and its nature remains to be elucidated.
Antibodies, Antinuclear↗