Acetylcholine Receptor Antibody Levels Research Articles

Markedly upregulated serum semaphorin 4A as a novel activity marker of myasthenia gravis.

Myasthenia gravis (MG) is an autoantibody-mediated disease of the neuromuscular junction. Semaphorin 4A (Sema4A) is involved in the activation of T cells in various inflammatory disorders. In this study, we aimed to investigate whether Sema4A is involved in the pathogenesis of MG. We measured serum Sema4A concentrations in 30 treatment-naïve MG patients with acetylcholine receptor (AChR) antibodies, 7 with muscle-specific tyrosine kinase (MuSK) antibodies and 21 normal controls. As a result, serum Sema4A levels were significantly higher in patients with AChR antibody-positive MG and MuSK antibody-positive MG than in controls (p ≤ 0.0001 for both MG groups). Serum Sema4A levels were correlated with AChR antibody levels (Spearman's ρ = 0.39, p = 0.03) and MG Foundation of America clinical classification classes (Spearman's ρ = 0.38, p = 0.04) in patients with AChR antibody-positive MG. In conclusion, high serum Sema4A levels may reflect T-cell activation, and this molecule could be a potential marker of disease activity in MG.

Serum immunoglobulin G level reduction is a predictor of short-term improvement in patients with myasthenia gravis undergoing plasmapheresis.

The aim of the study was to investigate the serological factors in predicting symptom improvement in myasthenia gravis (MG) patients who underwent plasmapheresis (PP). The relationship between symptom improvement and change in immunoglobin G (IgG) and acetylcholine receptor antibody (AchR-Ab) levels in 21 MG patients after PP was analyzed. Patients were divided into two groups: the favorable (n = 11) or unfavorable (n = 10) response groups around the median MG composite improvement rate (50 [29, 56]%) 2 weeks after a PP course. In all patients, the IgG reduction rate before and after PP was higher in the favorable than the unfavorable response group. In AChR-Ab-positive patients, IgG and AChR-Ab reduction rates were higher in the favorable than the unfavorable response group. IgG reduction rate is a predictor of symptom improvement in MG patients who underwent PP.

The relationship between serum iron levels and AChR-Ab and IL-6 in patients with myasthenia gravis.

To investigate the correlation between serum iron (SI) levels and acetylcholine receptor antibodies (AChR-Ab) and interleukin 6 (IL-6) in patients with myasthenia gravis (MG). A total of 76 patients with myasthenia gravis (MG group) between July 2015 to March 2018, and another 50 healthy subjects during the same period were selected for this study. SI levels in the peripheral blood serum of all participants were measured using the colorimetric method (a SI level of < 8.95 umol/L was considered the standard for SI deficiency). Enzyme-linked immunosorbent assays (ELISA) and radioimmunoassays (RIA) were used to detect the expression and levels of IL-6 and AChR-Ab in the peripheral blood of all participants. The presence and levels of IL-6 and AChR-Ab in the serum of MG patients and normal healthy subjects were compared. The levels of IL-6 and AChR-Ab in MG patients with normal SI levels and those with SI deficiency were analyzed. The SI deficiency rate, AChR-Ab positivity rate, AChR-Ab levels, and IL-6 levels in the MG group were significantly higher than those in the control group (73.68% vs. 26.00%, 81.58% vs. 0.00%, 1.05 ± 0.40 nmol/L vs. 0.21 ± 0.09 nmol/L, and 183.54 ± 35.26 ng/mL vs. 121.43 ± 28.45 ng/mL, respectively; all p-values were < 0.01). In MG patients, the levels of AChR-AB and IL-6 in the SI deficiency group were significantly higher than those in the normal SI group (1.15 ± 0.34 nmol/L vs. 0.81 ± 0.45 nmol/L and 193.12 ± 31.70 ng/mL vs. 156.74 ± 31.19 ng/mL, respectively; all p-values were < 0.01). The correlation analysis showed that SI levels were negatively correlated with AChR-AB and IL-6 levels in MG patients (r = -0.776, r = -0.663, both p-values were < 0.01). Iron deficiency in MG patients and SI levels are negatively correlated with AChR-Ab and IL-6 levels in MG patients.

Circulating CXCR5+ natural killer cells are expanded in patients with myasthenia gravis.

Myasthenia gravis (MG) is a classic autoantibody-mediated disease in which pathogenic antibodies target postsynaptic membrane components, causing fluctuating skeletal muscle weakness and fatigue. Natural killer (NK) cells are heterogeneous lymphocytes that have gained increasing attention owing to their potential roles in autoimmune disorders. This study will investigate the relationship between the distinct NK cell subsets and MG pathogenesis. A total of 33 MG patients and 19 healthy controls were enrolled in the present study. Circulating NK cells, their subtypes and follicular helper T cells were analysed by flow cytometry. Serum acetylcholine receptor (AChR) antibody levels were determined by ELISA. The role of NK cells in the regulation of B cells was verified using a co-culture assay. Myasthenia gravis patients with acute exacerbations had a reduced number of total NK cells, CD56dim NK cells and IFN-γ-secreting NK cells in the peripheral blood, while CXCR5+ NK cells were significantly elevated. CXCR5+ NK cells expressed a higher level of ICOS and PD-1 and a lower level of IFN-γ than those in CXCR5- NK cells and were positively correlated with Tfh cell and AChR antibody levels. In vitro experiments demonstrated that NK cells suppressed plasmablast differentiation while promoting CD80 and PD-L1 expression on B cells in an IFN-γ-dependent manner. Furthermore, CXCR5- NK cells inhibited plasmablast differentiation, while CXCR5+ NK cells could more efficiently promote B cell proliferation. These results reveal that CXCR5+ NK cells exhibit distinct phenotypes and functions compared with CXCR5- NK cells and might participate in the pathogenesis of MG.

Exploring the Potential Mechanism of Qi-Shen-Di-Huang Drug Formulary for Myasthenia Gravis (MG) based on UHPLC-QE-MS Network Pharmacology and Molecular Docking Techniques

Myasthenia gravis (MG) is a rare and refractory autoimmune disease, and Qi Shen Di Huang (QSDH) drug formulary is an in-hospital herbal decoction with proven clinical efficacy in treating MG. Currently, most of the research on the QSDH drug formulary has concentrated on its clinical efficacy, and there is a lack of systematic study on the material basis. The active compounds and their mechanism of action have not been entirely determined. Therefore, this study sought to identify the active compounds in the QSDH drug formulary and analyze the key targets and potential mechanisms. We used ultra-performance liquid chromatography Q Exactive-mass spectrometry (UHPLC-QE-MS) and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database to identify and screen 85 active ingredients corresponding to 59 potential targets (17 herbs) associated with myasthenia gravis, and further identified AKT1 as the primary core target and the PI3K/AKT signaling pathway as the most substantial enriched pathway. Molecular docking and UPLC-MS analysis identified quercetin, luteolin, wogonin, kaempferol, laccasein, and epigallocatechin gallate are the core compounds of the QSDH drug formulary. In vivo rat studies showed that the QSDH drug formulary reduced Lennon's clinical score and decreased acetylcholine receptor antibody levels in peripheral blood rats with experimental autoimmune myasthenia gravis. In addition, the QSDH drug formulary downregulated P-PI3K/PI3K and P-Akt/Akt protein expression. Collectively, these findings describe the role and potential mechanism of the QSDH drug formulary in the treatment of MG, which exerts potential value by acting on AKT targets and regulating the PI3K/AKT signaling pathway and providing a theoretical reference for QSDH drug formulary application in the clinical treatment of MG.

Renal Transplantation in Pure Autonomic Failure.

Renal Transplantation in Pure Autonomic Failure.

Optimization of the cut-offs in acetylcholine receptor antibodies and diagnostic performance in myasthenia gravis patients

ObjectiveThis study aims to establish an optimization procedure to define the cut-offs of quantitative assays for acetylcholine receptor antibody (AChRAb), evaluate their diagnostic performance in myasthenia gravis (MG), and explore the association with clinical features. MethodsSamples from a representative cohort of 77 MG patients, 80 healthy controls (HC) and 80 other autoimmune diseases (OAD) patients were tested using competitive inhibition ELISA and RIA. Raw values (OD and cpm) and processed values (inhibition rate, binding rate and concentration) were used to define the cut-offs with statistical methods, a rough method, and receiver operating characteristic (ROC) curve. Optimal cut-offs were selected by comparing false positive rates in HC and OAD individuals. The diagnostic performance was evaluated in whole MG cohort and subgroups. Agreement between ELISA and RIA for AChRAb positivity were examined with Kappa test and McNemar test. Clinical association with AChRAb was explored by comparison among subgroups and with Spearman rank correlation. ResultsThe optimal cut-offs for AChRAb positivity were determined as OD ≤ 1.79 for ELISA and cpm ≥ 1234.12 for RIA, which derived from statistical method and performed better than those derived from ROC curves. The sensitivity and specificity were 74.03%, 100% for ELISA, and 74.03%, 99.37% for RIA. There was good agreement between ELISA and RIA for AChRAb positivity in whole cohort and subgroups (weighted к ≥ 0.71, p < 0.01; McNemar test, p > 0.05). Levels of AChRAb were different in MG subgroups (p < 0.01). Correlation between Quantitative Myasthenia Gravis scores and AChRAb levels was moderate for ELISA and RIA (rs = -0.60 and 0.57, p < 0.01). ConclusionThe raw testing values of ELISA and RIA were found as optimal quantitative measures of AChRAb levels. There are good agreements on diagnostic performance between two assays. Quantitative values are more informative than positivity in association with clinical features.

Treatment of myasthenia gravis with the method of tonifying spleen and replenishing qi in traditional Chinese medicine: A protocol for systematic review and meta-analysis.

Background:Myasthenia gravis (MG) is an autoimmune disease that is associated with the production of autoantibodies. The symptoms of MG are mainly mediated by pathogenic antibodies directed against nicotinic acetylcholine receptors, resulting in a decrease in the number of acetylcholine receptors molecules on the postsynaptic membrane of the neuromuscular junction endplate, leading to clinical symptoms of muscle fatigue and weakness. At present, traditional Chinese medicine (TCM) treatment of MG has a better effect by tonifying spleen and replenishing qi. The purpose of this study was to systematically evaluate the efficacy and safety of TCM therapy for tonifying spleen and replenishing qi in the treatment of myasthenia gravis.Methods:We searched the following databases from their establishment until December 2021: PubMed, Cochrane Library, EMBASE, Web of Science, Springer, CNKI, Wanfang, China Biomedical Database, China Science and Technology Journal Database, Chinese Knowledge Infrastructure, China Clinical Trial Registry, and Baidu Scholars. The literature search language was limited to Chinese and English, and publication time and status were not limited. Randomized controlled trials (RCTs) were included. Two researchers independently searched and screened the articles, assessed their quality, and used the RevMan 5.4.1 software to perform a meta-analysis of the included literature.Results:This study compared the main outcome indicators: efficacy rate, recurrence rate, quality of life, and quantitative myasthenia gravis (QMG). Secondary outcome indicators were the clinical absolute score, TCM syndrome score, serum acetylcholine receptor antibody level, and electromyogram low-frequency repetitive nerve stimulation.Conclusion:This study aimed to evaluate whether the TCM method of tonifying spleen and replenishing qi is effective in the treatment of MG and to provide evidence-based data.Ethics and dissemination:The protocol of the systematic review did not require ethical approval because it did not involve human subjects. This article will be published in peer-reviewed journals and will be presented at conferences.

A Toddler with Juvenile Ocular Myasthenia Gravis: Clinical Experience

Background:Myasthenia gravis is an extremely rare autoimmune disorder affecting the neuromuscular junction. The incidence rate is 0.9-2.0 cases per 1 million children per year.Ocular myasthenia gravispresents as ptosis with extraocular motility restriction and is prone to be misdiagnosed as third nerve palsy and is difficult to diagnose in very young children.&#x0D; Case: A girl aged 2 years 6 months with clinical features with bilateral ptosis and was diagnosed as juvenile ocular myastenia gravis based on history, physical examination and other diagnostic proceduressuch as chest X-raywithin normal limit and no thymoma, the ice test showed positive result, electromyography (EMG) showed decrement response &gt;10%,progstigmin test showed positive result, andserum acetylcholine receptor antibody levels was 0.43 nmol/L (reference range : positive as &gt;0.40 nmol/L).&#x0D; Conclusion:Juvenile ocular myastenia gravis diagnostics can be established using simple examinations such as ice tests,prostigmin test to sophisticated examinations as systemic acetylcholinesterase antibodies. Management begins with a first-line drug, pyridostigmine, that is safe and effective. Disease monitoring and looking for etiology are very important for successful treatment.

Correlation of anti-γ/ε nicotinic acetylcholine receptor antibody levels with anti-desmoglein 1,3 antibody levels and disease severity in pemphigus vulgaris.

A role for nondesmoglein antigens in the pathogenesis of pemphigus vulgaris (PV) has been suggested in several studies. Acetylcholine receptors (AchR), are one of the most important groups of these antigens. However, the exact role of both antimuscarinic (m) and nicotinic (n) AchR antibodies (Abs) is still controversial. To evaluate anti-desmoglein (Dsg)1, Dsg 3 and anti-γ/ε nAchR Abs values in patients with PV before and 3months after rituximab (RTX) treatment, and to assess their correlation with disease severity. In total, 75 patients with PV (26 men, 49 women) who were planned to receive RTX were enrolled. Disease activity was assessed by using the Pemphigus Disease Area Index (PDAI). Using ELISA, anti-Dsg1,3 and anti-γ/ε nAchR Abs were determined at baseline and 3months after RTX treatment. At baseline, 53.33% patients had positive values for anti-Dsg1, 89.33% for anti-Dsg3 and 13.33% for anti-γ/ε nAchR Abs. All patients with positive anti-γ/ε nAchR Abs had the mucocutaneous phenotype. PDAI, anti-Dsg1,3 and anti-γ/ε nAchR values were dramatically decreased 3months after RTX infusion (P<0.001). There was a significant positive correlation between disease activity and anti-γ/ε nAchR values at baseline (P=0.04), whereas no significant correlation was observed between anti-Dsg1,3 and anti-γ/ε nAchR values at baseline and 3months after RTX infusion. The reduction in anti-γ/ε nAchR Abs with clinical improvement in this study may suggest a synergic role for anti-γ/ε nAchR Abs with anti-Dsg1,3 Abs, or it could be an epiphenomenon.

Rate of change in acetylcholine receptor antibody levels predicts myasthenia gravis outcome

ObjectiveTo investigate the association between changes in anti-acetylcholine receptor antibody (AChR Ab) levels induced by immunosuppressive treatment and myasthenia gravis (MG) prognosis at 1-year post-treatment in patients with MG.MethodsWe included...

Peripheral blood hsa-circRNA5333-4: A novel biomarker for myasthenia gravis

In this study, the potential of specific Circular RNAs (circRNAs) as novel peripheral blood biomarkers for myasthenia gravis (MG) was explored. We analyzed circRNAs in the peripheral blood of three normal controls and three MG patients using RNA microarray. Candidate circRNAs were validated in three independent cohorts by Quantitative Real-time polymerase chain reaction (qPCR). Eleven differentially expressed circRNAs were initially identified and four were confirmed in the first independent cohort. Hsa_circ_0076490 and hsa-circ_5333–4 had the largest areas under the curve (AUCs) of the receiver operating characteristics (ROC) and were validated in the second cohort. In the third cohort, hsa-circRNA5333-4 had a larger AUC: 0.864 (95% confidence interval [CI] = 0.801–0.928, P < 0.001), a stronger correlation with the Quantitative Myasthenia Gravis Score (qMG): r = 0.505 (P < 0.001) and was correlated with gender and acetylcholine receptor antibody levels (P < 0.05). So hsa-circRNA5333-4 represents a novel biomarker for the diagnosis and monitoring of MG.

Prediction of improvement after extended thymectomy in non-thymomatous myasthenia gravis patients.

It is popularly believed that myasthenia gravis (MG) patients show acetylcholine receptor antibody (AChRAb) production associated with the thymus (germinal centers, approximately 80%). It has been suggested that thymectomy can remove the area of autoantibody production. This study aimed to determine whether the solid volume of the thymus calculated using three-dimensional (3D) imaging could be used to predict the efficacy of thymectomy. Additionally, the study assessed the relationships of the solid volume with germinal centers, change in the serum AChRAb level, postoperative MG improvement, and prednisolone (PSL) dose reduction extent. This retrospective study included 12 consecutive non-thymomatous MG patients (9 female and 3 male patients), who underwent extended thymectomy at our institution over the last 10 years. The mean patient age was 43.3 ± 14.2 years (range, 12-59 years). The study assessed the number of germinal centers per unit area, change in the serum AChRAb level, postoperative MG improvement, PSL dose reduction extent, and solid volume of the thymus. The number of germinal centers per unit area was significantly correlated with the solid volume of the thymus. The PSL dose reduction extent tended to be correlated with the solid volume. Our findings suggest that the solid volume of the thymus can possibly predict steroid dose reduction. Additionally, the solid volume of the thymus in 3D images is the most important indicator for predicting the efficacy of extended thymectomy.

Is there a role for antibodies targeting muscarinic acetylcholine receptors in the pathogenesis of schizophrenia?

Muscarinic receptor dysfunction has been suggested to play an important role in the pathophysiology of schizophrenia. Recently, it has also become clear that immune reactivity directed against neurotransmitter receptors may play a pathogenic role in some cases of schizophrenia. The aim of this review is to summarize the case for muscarinic receptor dysfunction in schizophrenia and the evidence supporting the hypothesis that this dysfunction is related to the development of muscarinic receptor-targeting antibodies. The article reviews studies of muscarinic receptors and the presence and potential role(s) of anti-muscarinic acetylcholine receptor antibodies in people with schizophrenia. There is accumulating evidence that altered or deficient muscarinic signalling underlies some of the key clinical features of schizophrenia. Although the number of studies investigating anti-muscarinic acetylcholine receptor antibodies in schizophrenia is relatively small, they consistently demonstrate that such antibodies are present in a proportion of patients. This evidence suggests that these antibodies could have pathogenic effects or exist as a biomarker to an unknown pathophysiological process in schizophrenia. The presence of elevated levels of anti-muscarinic acetylcholine receptor antibodies may identify a subgroup of people with schizophrenia, potentially informing aetiopathogenesis, clinical presentation and treatment. To date, all studies have examined antibodies in participants with chronic schizophrenia, who have likely received antipsychotic medication for many years. As these medications modulate immune functions and regulate receptor densities, it is recommended that future studies screen for the presence of anti-muscarinic antibodies in people experiencing their first episode of psychosis.

Investigational RNAi Therapeutic Targeting C5 Is Efficacious in Pre-clinical Models of Myasthenia Gravis

Complement-mediated damage to the neuromuscular junction (NMJ) is a key mechanism of pathology in myasthenia gravis (MG), and therapeutics inhibiting complement have shown evidence of efficacy in the treatment of MG. In this study, we describe the development of a subcutaneously administered N-acetylgalactosamine (GalNAc)-conjugated small interfering RNA (siRNA) targeting the C5 component of complement that silences C5 expression in the liver (ALN-CC5). Treatment of wild-type rodents with ALN-CC5 resulted in robust and durable suppression of liver C5 expression. Dose-dependent serum C5 suppression was observed in non-human primates, with a lowering of serum C5 of up to 97.5% and the concomitant inhibition of serum complement activity. C5 silencing was efficacious in ameliorating disease symptoms in two standard rat models of MG, demonstrating the key role of circulating C5 in pathology at the NMJ. Improvement in disease activity scores and NMJ pathology was observed at intermediate levels of complement activity inhibition, suggesting that complete ablation of complement activity may not be required for efficacy in MG. The pre-clinical studies of ALN-CC5 and efficacy of C5 silencing in rat models of MG support further clinical development of ALN-CC5 as a potential therapeutic for the treatment of MG and other complement-mediated disorders.

Management and resolution of acquired myasthenia gravis in a carbimazole-treated hyperthyroid domestic shorthair cat

An 11-year-old male neutered domestic shorthair cat presented with acute onset signs of generalised weakness and neck ventroflexion. He had been diagnosed with hyperthyroidism two months previously and been treated...

CONGENITAL MYASTHENIC SYNDROMES AND MYASTHENIA: P.57Clinical features in juvenile myasthenia gravis in an Argentinian cohort

Juvenile myasthenia gravis (JMG) is an acquired autoimmune condition of the neuromuscular junction, caused by an antibody-mediated attack on the nicotinic acetylcholine receptor (AChR) and in a small minority associated with muscle-specific kinase (MuSK) antibodies. To determine the clinical and evolution related features of JMG in a 240 argentinian pediatric cohort. Cross sectional study of patients with JMG at three argentinian hospital, from January 1993 to January 2018. We included 240 patients by the symptoms, electrophysiology, AChR or MuSK antibody levels and a positive response to pharmacological treatment. We review medical charts in order to get clinical features from the onset symptoms, presence of antibody. Patients were classified by the MGF scale and compared by clinical features into the prepubertal and pubertal/postpubertal groups. Patients were followed for at least 3 years in order to know the final classification. We included 240 patients, 47% prepubertal, woman 1.85:1 (in prepubertal 1.09:1 and postpubertal 2.28:1), with age mean 7.2 (range 11 months to 17 years old). The onset symptoms were ptosis 83%, ocular symptoms 64% (43% generalized symptoms at 2 years follow-up), 30% had bulbar symptoms and y 12.5% had ventilatory compromised. The 22% (47% en prepubertal) ocular myasthenia gravis 7% had myasthenia crisis. In 78% of our cohort had AChR antibody (61% in prepubertal and 93% in postpubertal), 0.8% anti-Musk and 21% double-seronegative. We saw an stable-remission in 39 % (spontaneously 17%, 57% prepubertal and 29% were postpubertal). Minimal symptoms in 37%, pharmacological remission 19% and 13% remains symptomatic. This paper allow us to know abouts the clinical features, evolution and treatment response of the largest cohort described in Argentina. This encourage us to do a multicenter prospective studies in order to clarify this disease in children and to evaluate the new therapies.

Ganglionic Antibody Level as a Predictor of Severity of Autonomic Failure

ObjectiveTo assess antibody level as a test of autonomic failure (AF) associated with ganglionic nicotinic acetylcholine receptor antibody (AChR-Ab) autoimmunity. Patients and MethodsWe searched the Mayo Clinic laboratory database of 926 ganglionic AChR-Ab–seropositive patients seen at our institution between October 1, 1997, and April 1, 2015, for initial level of 0.05 nmol/L or higher and contemporaneous autonomic reflex screen (standardized evaluation of adrenergic, cardiovagal, and sudomotor functions) from which Composite Autonomic Scoring Scale (CASS) scores could be calculated. ResultsOf 289 patients who met inclusion criteria, 163 (56.4%) were women, median age was 54 years (range, 10-87 years), median antibody level was 0.11 nmol/L (range, 0.05-22.10 nmol/L), and median CASS total score was 2.0 (range, 0-10). Using receiver operating characteristic curve analysis, a level above 0.40 nmol/L predicted severe AF (CASS score, ≥7) with 92% specificity and 56% sensitivity. For at least moderate AF (CASS score ≥4 and anhidrosis ≥25%), a level of at least 0.20 nmol/L had 80% specificity and 59% sensitivity. Levels below 0.20 nmol/L were not predictive of the presence or absence of AF. For predicting orthostatic hypotension, ganglionic AChR-Ab level had excellent specificity above 0.4 nmol/L but lacked sensitivity. Autoantibodies to additional targets were present in 61 patients (21.1%). ConclusionGanglionic AChR-Ab level of at least 0.40 nmol/L is a moderately sensitive and highly specific marker for severe AF, as is a level of at least 0.20 nmol/L for moderate AF if CASS score is coupled with anhidrosis of 25% or more, among patients with suspected ganglionic AChR-Ab autoimmune autonomic ganglionopathy. Antibody levels of less than 0.20 nmol/L have little clinical importance in the absence of clinical AF.

False positive acetylcholine receptor antibodies in a case of unilateral chronic progressive external ophthalmoplegia: case report and review of literature

ABSTRACTMethods: We present a rare case with atypical presenting features of unilateral CPEO with a false positive Acetylcholine Receptor Antibody (AchRA) test resulting in diagnostic delay. We illustrate the unilateral nature of this case and demonstrate the caveats of performing myogenic ptosis correction in such patients. We also discuss the differential diagnosis of false positive AchRA, a test commonly performed in the investigation of ptosis.Results: A 34-year old female presented with a more than 3-year history of slowly-progressive, unilateral, right-sided restriction in eye movements and ptosis. Clinical examination showed EOM were grossly restricted in the right eye with a ptosis and normal in the left eye. Serum AchRA was positive on serum enzyme-linked immunosorbent assay (ELISA) however, following two months of oral pyridostigmine therapy there were no signs of clinical improvement. The initial serum sample sent was retested for AchRA by radio-immunoassay (RIA) which came back negative. Subsequently a muscle biopsy was requested which showed the presence of ragged red fibres.Conclusion: Unilateral ptosis and ophthalmoplegia is an unusual presentation for CPEO which characteristically produces bilateral symmetrical motility defects. In addition to Myasthenia Gravis elevated AchRA levels have been reported in other autoimmune conditions such as Primary biliary cirrhosis, Eaton Lambert syndrome and Graves’s ophthalmopathy. We also highlight the superiority of RIA versus ELISA in the detection of AchRA and illustrate the diagnostic challenge of investigating and managing myogenic ptosis in this complex cohort of patients.

Anti-acetylcholine receptor antibodies as a diagnostic marker for myasthenia gravis

Background Myasthenia gravis (MG) is a common primary disorder of neuromuscular transmission, which is characterized by fluctuating weakness of a certain voluntary muscles, particularly those innervated by motor nuclei of the brain stem, that is, ocular and mastication muscles, and caused by antibodies binding to components in the neuromuscular junction. Most MG cases demonstrate elevated serum levels of acetylcholine receptor (ACh-R) antibodies, which cause partial or complete inhibition of receptor function and complement-mediated focal lysis of the postsynaptic membrane. ACh-R antibodies are detected in the serum of more than 80–90% patients with generalized MG, in ~50% with ocular myasthenia, and rarely in healthy people. Aims The aim of our study is to determine the value of anti-ACh-R antibodies in diagnosis and prognosis of MG and to evaluate their sensitivity and specificity in comparison between different types of myasthenia. Patients and methods All patients were recruited from the outpatient clinic of Mataria Teaching Hospital on their first visit to neuropsychiatry clinic with suspicious symptoms of MG within 3 months. Our study included 90 women, of whom 60 patients had clinical symptoms suspicious of MG. The patients were classified into five groups: four groups according to Osserman classification and the fifth group included the seronegative patients. Their age ranged from 20 to 30 years. There was another group, the sixth group, which included 30 age-matched healthy controls. All patients were subjected to full history taking, general examination, and neurological examination to facilitate clinical assessment and staging of the disease according to Osserman classification and detection of ACh-R antibodies (binding, modulating and blocking antibodies), prostigmine test, repetitive nerve stimulation, and single-fiber electromyography stimulation tests. Result There was no significant difference between studied groups regarding age. Moreover, we found significant differences between them and the control group regarding the levels of ACh-R antibodies (binding, blocking, and modulating antibodies), but there were no significant differences between them regarding the extent of MG. There is no correlation between the studied groups and the level of acetylcholine, except for a weak positive correlation between the Osserman class and level of blocking receptor antibodies. Receiver operating characteristic curves showed that all the three types of antibodies had poor value for discrimination between MG subgroups. Moreover, there is a significant difference between the studied groups regarding prostigmine, repetitive nerve stimulation, and single fiber electromyography tests. Conclusion ACh-R antibody levels are of major importance as a noninvasive sensitive and specific diagnostic test for different types of myasthenia. However, they had no role in predicting the prognosis of different classes of the disease.