|Year : 2023 | Volume
| Issue : 1 | Page : 38-42
Severity and antibodies profile of seropositive myasthenia gravis
Amal M Alkhotani1, Nouf Alrishi2
1 Department of Medicine, Umm Al Qura University; Department of Neurology, King Abdullah Medical City, Mecca, Saudi Arabia
2 Department of Neurology, King Abdullah Medical City, Mecca, Saudi Arabia
|Date of Submission||27-Dec-2022|
|Date of Decision||07-Feb-2023|
|Date of Acceptance||08-Feb-2023|
|Date of Web Publication||15-Mar-2023|
Amal M Alkhotani
Department of Medicine, Umm Al Qura University, Mecca 24354
Source of Support: None, Conflict of Interest: None
Background: Myasthenia gravis (MG), an autoimmune disease, affects the neuromuscular junction. The impaired neuromuscular transmission results in fatigable muscle weakness among MG patients. Positive antibodies are found among MG patients. Aims: The main aim of this study is to evaluate the correlation of MG severity with their anti-muscle-specific kinase (MUSK) and anti-acetylcholine receptor (AChR) antibody status. Moreover, the study also identifies the correlation between the antibodies profile and the severity of a seropositive MG. Setting and Design: This retrospective cross-sectional study was conducted in the tertiary center of the western region of Saudi Arabia named King Abdullah Medical City (Makkah) over 8 years, from January 2011 to December 2019. Materials and Methods: This retrospective cross-sectional study was conducted in Saudi Arabia in King Abdullah Medical City (Makkah) over 8 years, from January 2011 to December 2019 was reviewed. Seventeen patients out of 27 MG patients came out to be seropositive. The correlation was investigated between severity and antibody status. Statistical Analysis: Data were collected in an Excel sheet, and statistical analysis was performed using SPSS 21 software. Results: The results showed that most patients (87.5%) were positive for AChR antibodies only, while others (12.5%) were positive for anti-MUSK and anti-AChR. Thymoma and crisis were observed in 100% with dual seropositivity and 21% with single seropositivity. Conclusion: The study concluded that a severely aggressive course of MG is present among patients. However, detailed clinical trial studies are required for conforming MG severity and dual seropositivity.
Keywords: Antibodies, lipoproteins, myasthenia gravis, seropositive
|How to cite this article:|
Alkhotani AM, Alrishi N. Severity and antibodies profile of seropositive myasthenia gravis. Saudi J Health Sci 2023;12:38-42
| Introduction|| |
Myasthenia gravis (MG) is an autoimmune neuromuscular disease. Several antibodies are recognized with MG.
The MG patients possess antibodies against acetylcholine receptors (AChRs). Striatal antibodies are found in a subset of MG patients, including antibodies against the alpha subunit of voltage-gated K + channel and titin. Patients with MG present with fatiguable weakness related to defect in neuromuscular transmission. MG had bimodal distrubution in women with peak at age of 30 and 50. In men incidence increase with age and peak after age of 60.a very late onset MG is a well recognized clinical condition in which patient presented at age of 65 or more., However, they had good prognosis with good response to treatment. The patient which has been suffering from MG have the a very specific clinical manifestations. They can present with ocular or generalized MG. The clinical characteristic are variable depending on autoantibodies status. The clinical characteristic of MG is determint by the demographic condition, antibody profile, comorbidities, and the intake of previous and present medicines. MG can be classifed into early onset MG if affect patuient less than 50 year of age or late onset (50-65) and very late onset MG (above ager of 65). MG is calssifed as early onset MG when it affect patient under age of 50 or late onset MG in patient above age of 50. Diagnosis of MG is particularly difficult in a very late onset MG. The presence of co-morbidities in the subset of patients make the diagnosis difficult. Several other condition can produce similar features to MG and should be carefully excluded., diagnosis of MG is established based on specific clinical features and supported by laboratory and electro-diagnostic studies. Presence of anti-AchRs or Anti-Musk antibodies confirm the diagnosis of MG. In a subset of patient who had a negative test for both anti-LRP4 should be assessed. A study showed that 9.2% of double seronegative MG had a positive anti-LRP4. Thymoma is found in 10-20% of patient with MG. Patient with thymoma tend to have a seropoasitive MG. Anti-AchRs are the most frequent antibodies associated with thymoma. Thymoma is staged based on TNM (tumor, node, metastasis system). In the presence of thymoma surgical resection is indicated. The outcome of thymoma depending on it is stage.,,
The aim of this study is to assess the severity of MG in relation to antibodies profile
| Materials and Methods|| |
This retrospective cross-sectional study was conducted in the tertiary center of the western region of Saudi Arabia named King Abdullah Medical City (Makkah) over 8 years, from January 2011 to December 2019.
This study included all the seropositive MG patients, and data were collected from patient charts. Patients with seronegative MG were excluded from the study. Electronic charts were reviewed to identify the positive anti-MUSK or anti-AChR Abs antibodies cases. Ethical approval was obtained from KAMC IRB. No study activities were started until IRB approval was obtained. Only patient record numbers were kept, and the investigators had access to the patient's data. The flowchart is presented in [Figure 1] regarding the antibodies profile of seropositive MG.
The MG's severity was determined according to the MG Foundation of America (MGFA) clinical classification, considering the severity of the disease at presentation. Duration, number of crisis and ICU admission were assessed. The severity was correlated to the seropositivity to the antibody and the presence of thymus pathology. Age, gender, clinical features, severity as indicated by MGFA clinical classification, ICU admission, days of ICU admission, number of crisis, duration of the crisis, antibodies profile, thymus pathology, and medications were the data variables obtained.
Data were analyzed using Statistical Package for the Social Sciences (SPSS) software version 21.0 (IBM, Chicago, Illinois, United States). Descriptive statistics were presented as frequencies and percentages for categorical variables, whereas the continuous variables were presented through mean, median, and standard deviation.
| Results|| |
Out of 19 patients with seropositive MG, most of them were <60-year-old (56.25%) and were male (62.5%). A total of five patients were reported with thymoma and one patient with thymus hyperplasia [Table 1]. Hypothyroidism as a comorbidity was reported among only one patient. [Table 2] presents laboratory findings of patients with seropositive MG. Out of 19 patients, 15 patients were reported with generalized (G) MG, followed by bulbar and ocular MG. The majority of the participants have shown single seropositivity to anti-AChR, while only two patients showed double seropositivity. The patients with double seropositivity had thymoma Stage B2. A total of five patients were reported with the crisis. All patients with double seropositivity had a recurrent crisis with prolonged ICU admissions.
|Table 2: Laboratory findings of patients with seronegative myasthenia gravis|
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| Discussion|| |
The most prevalent phenotype in MG patients was generalized myasthenia with mostly oculobulbar symptoms initially, as is usual in the elderly, and linked with a better long-term prognosis. A considerable proportion of the patients may even possess medical comorbidity, with the majority having more than one. Diabetes, hyperlipidemia, and hypertension were among the preventable cardiovascular risk factors identified. Furthermore, several patients had disorders that may contribute to the patient's overall functional impairment. Multiple comorbid diseases, along with hepatic and renal diseases, have been linked to poor outcomes in younger age groups; however, the presence of multiple comorbidities was not linked to the final myasthenic status.
The AchR-Ab radioreceptor Assay is to determine in vitro diagnostic semi-quantitative aspects of autoantibodies in human plasma and serum against the AChR. Antibodies are measured through this assay complexed with iodine labeled alpha-bungarotoxin (αBTX), precipitated with solubilized muscle AchR. Antibodies that bind to the receptor areas that are not sterically blocked by the αBTX have been detected., MG patients are presented with acetylcholine-receptor antibodies and polyclonal antibody response in MG. Different mechanisms allow the antibody to damage the AChRs based on cross-linkage antibodies with the AchR; blocked antibody of the AChRs, and complemented mediated destruction of junctional folds of the postsynaptic membrane.,,,
The neuromuscular junctions differ among different patients or even among other muscles of a single patient. Surprisingly, antibodies have a more dominant impact on degradation among some patients, while antibodies also produce a marked blockade of AChRs. This shows the difference in anti-AChR antibodies in their ability to produce muscle weakness. On the other hand, the titer does associate with the disease severity, and a reduction in titer means a preferable response to the treatment in an individual patient.
A strong association between a change in clinical condition and the anti-AchR concentration was notified throughout treatment with immunosuppression or prednisone after thymectomy. However, no differences were found in anti-AchR concentrations by the influence of anticholinesterases of deterioration caused by the emotion of infection. Anti-AchR antibodies detected through radioimmunoassay were not identified among 20% of patients with MG. It has been suggested that these patients potentially had antibodies alongside constituents of the neuromuscular junction that were not identified by the existing anti-AchR radioimmunoassay, such as MUSK antibody.,
Trinational antibodies can be utilized as prognostic determinants in MG as higher titers with more severe diseases. These antibodies might be beneficial to predict the course of the disease in patients with MG and for treatment regimens. T-cells have also been significant in the disease pathogenesis even though MG is widely anti-bodily mediated. It is suggested that these T-cells offer assistance to the B-cells through cytokines and surface molecules, which result in B-cell advancement and the secretion of AchR particular antibody.
In this study, patients found with double seropositivity were more likely to have worse disease in terms of recurrence of crisis and more ICU admissions. Both cases of double seropositivity have thymoma. The study results reported that most of the patients (87.5%) were positive for AChR antibodies, whereas others (12.5%) were positive for Anti-MUSK and Anti-AChR. Those patients with single seropositivity have had Thymoma in 21% of the cases, whereas dual seropositivity was reported in 100% of patients. Thymus hyperplasia was reported only in 7% of the single seropositivity cases. The crisis was reported at 21% in single seropositivity patients, whereas 100% in patients with dual seropositivity. About the line of treatment, 100% of those patients with single positivity have been on pyridostigmine, 71.4% taking steroids, and 61.4% receiving other immunosuppressant agents. Patients with dual seropositivity received pyridostigmine and other immunosuppressant agents in 100% of the cases but steroids in 50% of them.
A total of 24 cases of double seropositivity to anti-AChR and anti-MUSK have been reported in the literature. Most of those cases were naturally occurring MG with no relation to thymoma. However, nine patients developed double seropositivity after thymectomy. Around 85% of double seropositivity was associated with generalized MG, similar to the results. Only one case of double seropositivity to anti-AChR and anti-LRP4 was associated with invasive thymoma. The patient had severe MG in that report, similar to the study cases.
These findings raise the interesting possibility that the neuromuscular junction does not target the immune attack in seronegative MG. The myasthenic symptoms in seronegative patients for seropositive and seronegative patients are contributed by similar clinical severity. The explanation is provided about a myasthenic-like syndrome with elevated serum anti-ryanodine receptor antibodies regardless of abnormality in neuromuscular synaptic transmission.
There are several limitations in the present study. Being a retrospective study, the sample size of this study is limited, and it lacks comprehensive details concerning the comorbidities. Future studies need to survey a larger cohort of younger MG patients. A larger sample size would help clear recognition of the impact on their overall health status or quality of life.
| Conclusion|| |
The study reported no correlation between serum concentration of anti-AChR antibodies and MG severity, considering the variety of etiopathogenesis of MG. Moreover, an aggressive course of MG and association with thymoma are likely found among patients with dual seropositivity. It is recommended to consider sending for Anti-MUSK and Anti-AChR antibodies while working up patients to MG, even if they were only positive for AChR antibodies. Future studies should examine neuromuscular transmission to identify the pathophysiology of seronegative MG subtypes in different muscle groups. In addition, clinical observations may complement experimental studies improving the understanding of functions performed by the neuromuscular junction. Moreover, the differences among patients in response to clinical presentation and therapies can be understood by classifying MG specificities.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2]