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1.
Eur J Neurol ; 24(8): 999-1005, 2017 08.
Article in English | MEDLINE | ID: mdl-28544133

ABSTRACT

BACKGROUND AND PURPOSE: The aim of this study was to describe clinical and paraclinical characteristics of all Danish patients who tested positive for anti-voltage-gated potassium channels (VGKC)-complex, anti-leucine-rich glioma-inactivated 1 (LGI1) and anti-contactin-associated protein-2 antibodies in the serum/cerebrospinal fluid between 2009 and 2013 with follow-up interviews in 2015 and 2016. METHODS: We evaluated antibody status, symptoms leading to testing, course of disease, suspected diagnosis and time of admission as well as diagnosis and treatment. All magnetic resonance imaging, electroencephalography and 18 F-fluorodeoxyglucose positron emission tomography scans were re-evaluated by experts in the field. RESULTS: A total of 28/192 patients tested positive for VGKC-complex antibodies by radioimmunoassay and indirect immunofluorescence; 17 had antibodies to LGI1 and 6/7 of the available cerebrospinal fluids from these patients were seropositive. These 17 patients all had a clinical phenotype appropriate to LGI1 antibodies. The remaining 11 were LGI1 negative (n = 4) or not tested (n = 7). Of these, two had a phenotype consistent with limbic encephalitis. The remaining phenotypes were Guillain-Barré syndrome, Creutzfeldt-Jakob disease, neuromyotonia and anti-N-methyl-D-aspartate receptor encephalitis. Magnetic resonance imaging abnormalities were demonstrated in 69% of the LGI1-positive patients. Two patients with normal magnetic resonance imaging demonstrated temporal lobe hypermetabolism using 18 F-fluorodeoxyglucose positron emission tomography. Abnormal electroencephalography recordings were found in 86% of the patients. Upon follow-up (median 3.2 years), the median modified Rankin Scale score of anti-LGI1-positive patients was 2 and only two patients reported seizures in the past year. CONCLUSIONS: Patients diagnosed with anti-LGI1 autoimmune encephalitis increased significantly from 2009 to 2014, probably due to increased awareness. In contrast to seropositive anti-VGKC-complex patients, all anti-LGI1-positive patients presented with a classical limbic encephalitis. The majority of patients recovered well.


Subject(s)
Autoantibodies/blood , Encephalitis/immunology , Hashimoto Disease/immunology , Limbic Encephalitis/immunology , Potassium Channels, Voltage-Gated/immunology , Proteins/immunology , Adult , Aged , Aged, 80 and over , Cohort Studies , Encephalitis/diagnostic imaging , Female , Hashimoto Disease/diagnostic imaging , Humans , Intracellular Signaling Peptides and Proteins , Limbic Encephalitis/diagnostic imaging , Magnetic Resonance Imaging , Male , Membrane Proteins/immunology , Middle Aged , Nerve Tissue Proteins/immunology
2.
Eur J Neurol ; 6(5): 555-63, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10457388

ABSTRACT

We studied 65 patients with myasthenia gravis (MG). Clinical, neurophysiological, immunological, and histological findings suggested the coexistence of a presumed autoimmune myopathy. The clinical features were persistent pyridostigmine-resistant weakness and atrophy of striated muscles. The myopathy was found more often in patients with late-onset MG than in those with early-onset (37% vs 13%). Patients with myopathy were also prone to have other immune disorders (47% vs 13%). Elevated titres of antibodies against titin were detected more often in patients with electromyography (EMG) evidence of myopathy than in the sera of those without, and only in late-onset MG cases.


Subject(s)
Autoantibodies/immunology , Calmodulin-Binding Proteins/immunology , Muscle Proteins/immunology , Myasthenia Gravis/immunology , Myasthenia Gravis/physiopathology , Protein Kinases/immunology , Adolescent , Adult , Age of Onset , Connectin , Electromyography , Female , Humans , Male , Middle Aged , Muscle Weakness/physiopathology , Muscle, Skeletal/pathology , Myasthenia Gravis/pathology
3.
Dan Med Bull ; 43(1): 1-10, 1996 Feb.
Article in English | MEDLINE | ID: mdl-8906977

ABSTRACT

The annual incidence rate of myasthenia gravis (MG) was estimated as 4.6 per million population, and the rate was found to be constant in calendar-time. Age- & sex-specific incidence rates disclosed a bimodal appearance for both sexes. According to the epidemiological data, the age limit between early onset and late onset of MG should be set at 50 years. The point prevalence rate has increased in time from 41 per million population in 1950 to 77 in 1988, and model calculation predicts an increased rate of 83 in year 2000. This reflects an improvement in the prognosis of MG. Standardized mortality rate for MG was estimated as 1.87. The total patient population was weighted 6 to 4 with predominance of females. A decrement of the muscle action potential (AP) and of the muscle twitch (TW) was found in 72% and 49% of the cases respectively, the diagnostic yield being proportional to the severity of MG. Post-tetanic facilitation of AP and TW was found in 25% and 20% of the cases respectively. The analogue estimates for post-tetanic exhaustion were 44% and 25% respectively. An abnormal staircase phenomenon was present in 37% of MG patients. Neurophysiological evidence of myopathy, which was not correlated to the degree of neuromuscular transmission failure, was found in 19% of the patients, more often in cases with late onset than in those with early onset (31% compared with 11%). The occurrence of myopathy was associated with pathological muscular biopsy (78%), and with anti-striated muscle antibodies (53%) suggesting that a myopathy of possibly autoimmune origin may coexist with MG. The overall diagnostic sensitivity of anti-AChR antibodies RIA was found to be 88%, the positivity being proportionate to the clinical severity of MG (ocular MG: early onset 71%, late onset 88%; severe generalized MG: early onset 89%, late onset 98%). The finding of anti-AChR antibodies is highly specific for MG (>99.9%). The distribution of antibodies titres was approximately lognormal. The concentration of the antibodies correlated with the clinical severity of the disease, female or male gender, and the pathology of the thymus gland. The improved outlook for MG during the last 4 decades may be ascribed to the combined results of all the new modalities of treatment. Experimental results towards selective plasma exchange are expounded. As opposed to MG patients with hyperplasia or involution of the thymus gland, thymoma cases exhibited exacerbation of the clinical course and also of the anti-AChR antibody titres after thymectomy. Possible steps to circumvent the therapeutical impasse in thymoma cases are discussed, such as combined immunosuppressive therapy along with surgery or conservative treatment for as long as possible.


Subject(s)
Antibodies/therapeutic use , Myasthenia Gravis/physiopathology , Myasthenia Gravis/therapy , Receptors, Cholinergic/immunology , Synaptic Transmission/physiology , Adult , Aged , Female , Humans , Male , Middle Aged , Myasthenia Gravis/epidemiology
4.
Acta Neurol Scand ; 90(1): 56-66, 1994 Jul.
Article in English | MEDLINE | ID: mdl-7941959

ABSTRACT

It appeared from this prospective and non-randomized study, that the removal of thymomas in myasthenia gravis (MG) patients resulted in rapid exacerbation of the clinical severity of the disease and of anti-acetylcholine receptor antibodies titres, which peaked after about 300 days and continued for up to 2 years. Long-term follow-up after thymomectomy (mean duration +/- SEM after surgery 5.5 +/- 0.8 years) showed that the immunological and clinical state observed prior to surgery was eventually restored, but long-term benefit attributable to surgery could not be demonstrated. Non-thymoma MG cases, however, exhibited post-operative amelioration in clinical course and decreasing antibodies titres, both of which were already significant one year after surgery, and additional improvement was observed at the time of long-term follow-up (mean 4.3 +/- 0.5 years). Furthermore, the prognosis for MG patients not operated on was also favourable. It is suggested that the occurrence of thymomas is linked to genetic factors and that neoplasia of the thymus may be part of immunoregulatory mechanisms with predominance of inhibition.


Subject(s)
Autoimmune Diseases/immunology , Myasthenia Gravis/immunology , Thymectomy/adverse effects , Thymoma/immunology , Thymoma/surgery , Thymus Neoplasms/immunology , Thymus Neoplasms/surgery , Adolescent , Adult , Antibodies/analysis , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prognosis , Prospective Studies , Radioimmunoassay , Receptors, Cholinergic/immunology
5.
J Neuroimmunol ; 51(1): 63-8, 1994 Apr.
Article in English | MEDLINE | ID: mdl-8157737

ABSTRACT

Acetylcholine receptor (AChR) from the human rhabdomyosarcoma cell line TE671 was compared with that of human ischaemic muscle AChR as a source of the antigen for the diagnosis of myasthenia gravis (MG). The sera, which were anti-TE671 cell AChR antibody-negative, all came from patients with low anti-human muscle AChR antibody titers. None of the sera that were seronegative as a result of the human muscle AChR RIA became positive with TE671 cell AChR. The overall sensitivity was 7% less using TE671 cell AChR. The lower sensitivity was observed irrespective of the clinical form of MG. It also appeared from this study that epitopes specific to the junctional isoform of human AChR are essential for the detection of low antibody titers, which accounts for this feature, since TE671 cells only express the extrajunctional isoform of AChR in the surface membrane. Accordingly, AChR from cell line TE671 cannot replace human muscle AChR in the conventional diagnostic immunoprecipitation RIA. There are, however, many other useful implications of AChR from cell line TE671.


Subject(s)
Antibodies/analysis , Myasthenia Gravis/immunology , Receptors, Cholinergic/immunology , Rhabdomyosarcoma/immunology , Antigens/immunology , Humans , Muscles/immunology , Precipitin Tests , Radioimmunoassay , Rhabdomyosarcoma/pathology , Sensitivity and Specificity , Tumor Cells, Cultured
6.
J Cereb Blood Flow Metab ; 14 Suppl 1: S12-8, 1994 Jan.
Article in English | MEDLINE | ID: mdl-8263066

ABSTRACT

Blood-brain barrier (BBB) passage of the flow tracer ethylenediylbis-L-cystein diethylester (bicisate, ECD) was measured repeatedly in five patients by means of the intravenous (i.v.) double-indicator technique using 24Na+ as an intravascular cotracer. After i.v. injection, the arterial concentration curve of 99mTc-bicisate was delayed and dispersed compared with that of the intravascular cotracer, presumably due to lung retention of the flow tracer. The corrected cerebral venous output curves were fitted using a three-compartment model with four parameters. At resting cerebral blood flow (CBF) values, the unidirectional brain extraction was 0.57 +/- 0.05, the permeability-surface area product for passage from blood to brain (PS1) was 0.48 +/- 0.07 ml/g/min, and the distribution volume for bicisate was 0.74 +/- 0.20 (mean +/- SD). In a single patient, BBB transport after i.v. injection of bicisate was compared with that of a similar flow tracer, d,l-hexamethylpropyleneamine oxime (HM-PAO), and similar values were found for the two tracers. In 19 rats, the brain extraction of bicisate was measured by means of the intracarotid double-indicator technique. The brain extraction was measured at resting, decreased, and increased CBF values. Low CBF values were obtained by hyperventilation and high values by hypercapnia. The degree of backflux of tracer from brain to blood was evaluated by means of the three-compartment model and was found to be negligible in these experiments. The brain extraction was 0.70 +/- 0.1 and PS1 was 0.94 +/- 0.27 ml/g/min. During hypercapnia, CBF increased from 0.77 to 1.09 ml/g/min, leading to a significant decrease in brain extraction, from 0.70 to 0.56.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Brain/metabolism , Cysteine/analogs & derivatives , Organotechnetium Compounds/pharmacokinetics , Adult , Animals , Arteries , Biological Transport , Blood-Brain Barrier , Cerebrovascular Circulation , Female , Humans , Male , Middle Aged , Organotechnetium Compounds/blood , Organotechnetium Compounds/chemistry , Oximes/pharmacokinetics , Rats , Rats, Wistar , Sodium Radioisotopes , Tissue Distribution , Veins
7.
J Neurol Neurosurg Psychiatry ; 56(5): 496-504, 1993 May.
Article in English | MEDLINE | ID: mdl-8505642

ABSTRACT

A multivariate analysis of anti-acetylcholine receptor (AChR) antibodies and clinical parameters other than treatment (modified Osserman groups, age, type of onset, sex, and thymus pathology) was performed for all incident (n = 366) myasthenia gravis (MG) cases in its white population in Denmark during the past 15 years. Sera from 244 healthy individuals and from 295 patients with diseases other than MG were analysed as controls. Formal statistics for the anti-AChR antibodies assay (immunoprecipitation RIA using crude human AChR extract) were calculated. The distribution of antibodies titres greater than 0.1 nMole/l was found to be approximately lognormal. For MG patients the 95% reference interval was 0.2-1549 nMoles/l, and in control sera the range was 0.0-0.4 nMole/l. Using 0.5 nMole/l as the cut-off level and regarding all results less than this value as normal titres, it appeared that the assay was highly specific (> 99.99%) for MG. In a population of MG patients significance should be attributed to values in the range 0.3-0.4 nMole/l. The overall diagnostic sensitivity was found to be 88%. The sensitivity appeared to be proportionate to clinical severity of MG. The percentage with a normal titre was higher (16%) for early onset of MG, compared with 7% for late onset. No significant difference in relation to the frequency of "negative titre" was found in relation to sex. Anti-AChR antibodies titre was found to correlate with clinical severity, female or male gender, and pathology of thymus. The groups of MG patients were not matched for the various clinical parameters but multiple regression analysis controlling for these variables revealed independent effects of clinical severity and sex though not of age. Normal thymus (including involuted gland) and thymoma were correlated with low to intermediate tires, and hyperplastic thymus with high level of antibodies. The clinical implementation of anti-AchR antibodies is reviewed from 1976 and up to the present. The problems with false positive results are thoroughly expounded.


Subject(s)
Antibodies/blood , Myasthenia Gravis/diagnosis , Receptors, Cholinergic/immunology , Antibodies/immunology , Female , Humans , Male , Models, Theoretical , Myasthenia Gravis/blood , Myasthenia Gravis/immunology , Precipitin Tests , Receptors, Cholinergic/analysis , Sex Factors , Thymoma/diagnosis , Thymoma/pathology , Thymus Gland/pathology , Thymus Hyperplasia/pathology , Thymus Neoplasms/diagnosis , Thymus Neoplasms/pathology
8.
Electroencephalogr Clin Neurophysiol ; 89(2): 73-87, 1993 Apr.
Article in English | MEDLINE | ID: mdl-7683605

ABSTRACT

Electrical and mechanical responses to single shocks, slow and fast nerve stimulation (RNS), quantitated EMG, anti-acetylcholine receptor (AChR) and anti-striated muscle (SM) antibodies (ab) were determined in 145 patients with myasthenia gravis (MG). Anti-AChR ab were found in 93% of the myasthenic sera. Decrement of muscle and mechanical responses occurred in 72% and 49%, respectively, the diagnostic yield being positively related to severity of MG. Anti-AChR ab were found in 81% of patients without RNS abnormalities. Decrement at RNS occurred in 33% of the cases without anti-AChR ab compared with 78% of those with elevated titres. Regional curare test (RCT) was diagnostic in 75% of cases with normal RNS. As the combined diagnostic yield of RNS and anti-AChR ab was 96%, RCT and single fibre EMG are rarely indicated. Post-tetanic facilitation and exhaustion, and an abnormal staircase phenomenon occurred in 25%, 44% and 37%, respectively. None of these parameters correlated with severity, type or onset of MG. EMG evidence of myopathy, positively correlated with the presence of anti-SM ab, occurred in 19% of patients examined, 3 times more frequent in those with late onset of MG than in those with early onset; thus myopathy of possible autoimmune origin may coexist with MG. An adequate electrophysiological diagnostic strategy for MG patients is proposed.


Subject(s)
Myasthenia Gravis/physiopathology , Adult , Autoantibodies/blood , Curare , Edrophonium , Electric Stimulation , Electromyography , Evoked Potentials/physiology , Female , Humans , Male , Middle Aged , Myasthenia Gravis/metabolism , Neuromuscular Junction/physiology , Physical Stimulation , Predictive Value of Tests , Receptors, Cholinergic/immunology , Synaptic Transmission/physiology
10.
Arch Neurol ; 48(7): 733-9, 1991 Jul.
Article in English | MEDLINE | ID: mdl-1859301

ABSTRACT

The incidence of myasthenia gravis (MG) was found to be constant in calendar time. The mean annual incidence rate was 4.4 per million population. Age- and sex-specific incidence rates disclosed a bimodal appearance for both sexes, with a peak age at onset located in the early-onset group and another peak for late onset of MG. Early onset of MG appeared 10 years later for male individuals than for female individuals, whereas the peak for late onset of MG was located at the same age for both sexes. It is suggested that the separation between early onset and late onset of MG should be at the age of 50 years for both sexes, rather than at 35 to 40 years as accepted in most studies. The prevalence of MG has increased in time. On January 1, 1988, the point prevalence rate was 77 per million population (female subjects, 96, and male subjects, 57). This reflects an improvement in prognosis despite the fact that life expectancy was found to be significantly lower for MG patients than that of the sex- and age-matched population. The factors causing increased mortality were found to be operative throughout the duration of the disease. Maximum severity of disease was reached within 2 years from onset in 78% of the cases, and more than 50% of all MG-related deaths occurred during the same period. In the course of MG, 70% of all patients experience generalized muscular weakness, and 30% to 40% also suffer from respiratory problems.


Subject(s)
Myasthenia Gravis/epidemiology , Denmark/epidemiology , Female , Humans , Male , Myasthenia Gravis/mortality , Population Surveillance
11.
Psychopharmacology (Berl) ; 101(1): 43-6, 1990.
Article in English | MEDLINE | ID: mdl-2188276

ABSTRACT

In order to examine if the nootropic drug, aniracetam, was capable of improving cognitive performance, 44 subjects suffering from chronic psychosyndrome after long-term exposure to organic solvents were included in a randomized, double-blind, placebo-controlled, cross-over study. The treatment periods were 3 months with aniracetam 1 g daily and 3 months with placebo. Neuropsychological tests as well as a physical and neurological examination were performed at entry into the study and after each treatment period, together with an evaluation of the subjects' overall condition. Neither the doctors' nor the subjects' own assessment of the overall condition indicated that the trial medication had had any effect. No significant changes in neuropsychological symptoms were observed. A statistically significant difference in favour of antiracetam was found in only 1 of the 19 neuropsychological test measures, namely a test for constructional ability. However, in another test on visuo-spatial function, a statistically significant result was found in favour of placebo. Thus, aniracetam was found to be ineffective in the treatment of subjects suffering from chronic psychosyndrome after long-term exposure to organic solvents.


Subject(s)
Psychoses, Substance-Induced/drug therapy , Pyrrolidinones/therapeutic use , Solvents/toxicity , Adult , Double-Blind Method , Female , Humans , Male , Middle Aged , Psychological Tests , Psychoses, Substance-Induced/psychology , Randomized Controlled Trials as Topic
12.
J Neuroimmunol ; 22(2): 123-7, 1989 Apr.
Article in English | MEDLINE | ID: mdl-2647782

ABSTRACT

Protein A-Sepharose and tryptophan polyvinyl alcohol affinity gels have been evaluated as possible agents for the selective, extracorporeal removal of anti-acetylcholine receptor (AChR) antibodies from the sera of patients with myasthenia gravis. Protein A-Sepharose was shown to be very effective. Specific anti-AChR IgG antibodies of subclasses 1 and 2 were reduced to the same extent (i.e. from 50 to 60% decrease) as the total IgG, although the latter was present at concentrations more than a 1000-fold greater. Anti-AChR antibody of subclass IgG3 was less effectively adsorbed. A full-scale in vitro experiment using one plasma volume and an automatic continuous monitor demonstrated the removal of 43% of the circulating anti-AChR antibodies and the IgG within 70 min, which is comparable to the amount removed by the present, unselective, membrane plasma exchange technique. In contrast, tryptophan polyvinyl alcohol was not effective in immunoadsorption under these circumstances.


Subject(s)
Antibodies/immunology , Immunosorbent Techniques , Myasthenia Gravis/therapy , Plasma Exchange , Receptors, Cholinergic/immunology , Humans , Immunoglobulin G/immunology , Immunoglobulin G/metabolism , Myasthenia Gravis/immunology , Receptors, Cholinergic/metabolism , Staphylococcal Protein A/immunology , Staphylococcal Protein A/metabolism
13.
Stroke ; 19(11): 1345-53, 1988 Nov.
Article in English | MEDLINE | ID: mdl-3188119

ABSTRACT

Stroke incidence in Copenhagen, Denmark was recorded in a random population sample of 19,327 persons invited for two health examinations with 5 years' interval from 1976 to 1983. Stroke incidence increased exponentially with age. After adjustment to the age and sex distribution of the Danish population in 1980, the estimated incidence of first stroke was 1.41/1000 women and 2.48/1000 men; the total incidence was 1.94/1000 population. Risk factor analysis was based on the initial examination of 13,088 persons greater than 35 years old without previous stroke who responded to the first invitation, in whom 295 first strokes were subsequently observed. We used the regression model of Cox. However, our use of this model differs from the somewhat automatic procedures normally used to develop prognostic models. Evaluation of the causative effect of a particular risk factor requires that the direction of mutual influences between the factor in question and other risk factors is established/postulated. Among the 16 potential risk factors for stroke we examined, significant effects were found for age, sex, household income, smoking habits, systolic blood pressure, diabetes, plasma cholesterol concentration, ischemic heart disease, and atrial fibrillation. No significant effect could be demonstrated for a positive family history of stroke, years of school education, marital status, alcohol consumption, daily use of tranquilizers, body mass index, or postmenopausal hormone treatment.


Subject(s)
Cerebrovascular Disorders/epidemiology , Adult , Aged , Atrial Fibrillation/complications , Cerebrovascular Disorders/etiology , Cholesterol/blood , Denmark , Diabetes Complications , Female , Humans , Hypertension/complications , Hypertension/therapy , Income , Male , Middle Aged , Models, Theoretical , Risk Factors , Sex Factors , Smoking
14.
Clin Exp Immunol ; 67(1): 82-8, 1987 Jan.
Article in English | MEDLINE | ID: mdl-3621677

ABSTRACT

The concentrations of IgG subclass antibodies (Ab) to acetylcholine receptor (AchR) were quantified in 36 patients with myasthenia gravis (MG) treated with pyridostigmine only, and in eight patients who underwent thymectomy, using an IgG subclass-specific immunoprecipitation assay. IgG1, IgG2, IgG3, and IgG4 subclass Ab to AchR were present in 100%, 33%, 64% and 39% of the pyridostigmine-treated patients, respectively. The concentration of IgG1 Ab increased significantly with disease severity as graded by the Osserman-Genkins classification (rs = 0.37, P less than 0.05). IgG1 and IgG3 subclass protein concentrations were significantly higher (P less than 0.0003) in the 36 pyridostigmine-treated MG patients than in 44 age- and sex-matched healthy subjects. Thymectomy induced an appreciable reduction in anti-AchR IgG1 concentration in two patients, whereas six patients showed no changes in Ab to AchR. The results support the hypothesis that binding of anti-AchR IgG1 and IgG3 on AchR in the neuromuscular junction followed by complement-mediated cell lysis or phagocytosis, may play a role in the pathogenesis of MG.


Subject(s)
Immunoglobulin G/analysis , Myasthenia Gravis/immunology , Receptors, Cholinergic/immunology , Humans , Immunoglobulin Allotypes/analysis , Immunoglobulin G/classification , Pyridostigmine Bromide/therapeutic use
15.
Br J Psychiatry ; 149: 323-9, 1986 Sep.
Article in English | MEDLINE | ID: mdl-3779299

ABSTRACT

Three groups of torture victims were studied with the aim of establishing a concept of psychotherapy for such victims. Analysis of the first group, consisting of 200 case-reports made by Amnesty International medical groups, resulted in a general outline of the psychological methods of torture and their main impact on the victims. A second group of 24 torture victims was examined by the authors, and a quantitative assessment of long-term neuropsychological complaints and a qualitative insight into these symptoms achieved. In-depth interviews with victims in the third group which, consisted of the victims from the second group and six others, together with the results from the other two groups, formed the basis of a concept of psychotherapy for torture victims.


Subject(s)
Psychotherapy , Torture , Adult , Anxiety/complications , Humans , Male , Mental Disorders/etiology , Mental Disorders/physiopathology , Mental Disorders/rehabilitation , Methods , Stress, Psychological/etiology , Time Factors
16.
J Immunol Methods ; 83(2): 249-58, 1985 Nov 07.
Article in English | MEDLINE | ID: mdl-3902978

ABSTRACT

Monoclonal anti-human IgG subclass antibodies have been used in an immunoprecipitation assay for the determination of anti-acetylcholine receptor IgG subclasses in plasma from patients with myasthenia gravis. Solubilized acetylcholine receptors labelled with 125I-alpha-bungarotoxin were incubated with patient plasma. Monoclonal mouse antibodies to human IgG subclasses 1-4 were added to the incubation and finally precipitated with anti-mouse IgG antibody. A maximal IgG subclass precipitation of 62-76% was determined with 125I-labelled myeloma IgG subclasses 1-4 added to normal human plasma. The anti-IgG subclass antibodies were added in excess which ensured that the precipitation of IgG2, IgG3 or IgG4 were unchanged, and that of IgG1 was only reduced by 17%, when the plasma IgG concentration was increased by a factor of two. The anti-IgG subclass antibodies were highly specific for their complementary subclasses. Determination of the IgG subclass of the anti-acetylcholine receptor antibodies from 8 patients with myasthenia gravis showed that IgG1 and IgG3 antibodies are predominant. This may support the hypothesis that complement mediated lysis of the neuromuscular end-plate plays a pathogenetic role in myasthenia gravis.


Subject(s)
Autoantibodies/classification , Immunoglobulin G/classification , Immunologic Techniques , Myasthenia Gravis/immunology , Receptors, Cholinergic/immunology , Antibodies, Monoclonal , Antibody Specificity , Autoantibodies/analysis , Chemical Precipitation , Dose-Response Relationship, Immunologic , Humans
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