Specific Tyrosine Kinase Antibodies Research Articles

Juvenile Generalized Myasthenia Gravis: Presented as Unilateral Blepharoptosis and Successfully Managed with Pulse Intravenous Methylprednisolone

Myasthenia Gravis is a rare autoimmune disorder of childhood and this is rarer in South Asia. We present a pre-pubertal 7 year old female child of seropositive Generalized Juvenile Myasthenia Gravis. She presented with unilateral blepharoptosis and later generalized symptoms appeared. Ice-pack test, Neostigmine challenge test and acetylcholine receptor antibody test were positive. Serum muscle specific tyrosine kinase antibody test was normal. She did not have thymic abnormalities. She did not respond to high dose (26 mg/kg/day) of Pyridostigmine and oral Prednisolone (2 mg/kg/day), but was successfully treated with a combination of pulse intravenous Methylprednisolone (30 mg/kg once a month for 6 months) and daily doses of oral Prednisolone (2 mg/kg/day) along with Pyridostigmine without significant side effects. This combination can be considered a potential inexpensive treatment for Juvenile Myasthenia Gravis in a resource limited area where other immunosuppressive treatments such as intravenous immunoglobulin is expensive and unaffordable.

Circulating miRNAs as Potential Biomarkers in Myasthenia Gravis: Tools for Personalized Medicine.

Myasthenia gravis (MG) is an autoimmune disease caused by antibodies which attack receptors at the neuromuscular junction. One of the main difficulties in predicting the clinical course of MG is the heterogeneity of the disease, where disease progression differs greatly depending on the subgroup that the patient is classified into. MG subgroups are classified according to: age of onset [early-onset MG (EOMG; onset ≤ 50 years) versus late-onset MG (LOMG; onset > 50 years]; the presence of a thymoma (thymoma-associated MG); antibody subtype [acetylcholine receptor antibody seropositive (AChR+) and muscle-specific tyrosine kinase antibody seropositive (MuSK+)]; as well as clinical subtypes (ocular versus generalized MG). The diagnostic tests for MG, such as antibody titers, neurophysiological tests, and objective clinical fatigue score, do not necessarily reflect disease progression. Hence, there is a great need for reliable objective biomarkers in MG to follow the disease course as well as the individualized response to therapy toward personalized medicine. In this regard, circulating microRNAs (miRNAs) have emerged as promising potential biomarkers due to their accessibility in body fluids and unique profiles in different diseases, including autoimmune disorders. Several studies on circulating miRNAs in MG subtypes have revealed specific miRNA profiles in patients’ sera. In generalized AChR+ EOMG, miR-150-5p and miR-21-5p are the most elevated miRNAs, with lower levels observed upon treatment with immunosuppression and thymectomy. In AChR+ generalized LOMG, the miR-150-5p, miR-21-5p, and miR-30e-5p levels are elevated and decrease in accordance with the clinical response after immunosuppression. In ocular MG, higher levels of miR-30e-5p discriminate patients who will later generalize from those remaining ocular. In contrast, in MuSK+ MG, the levels of the let-7 miRNA family members are elevated. Studies of circulating miRNA profiles in Lrp4 or agrin antibody-seropositive MG are still lacking. This review summarizes the present knowledge of circulating miRNAs in different subgroups of MG.

Simultaneous Presence of Acetylcholine Receptor and Muscle Specific Tyrosine Kinase Antibodies in Myasthenia Gravis

Myasthenia gravis (MG) is known as an autoimmune disorder which affects transmission in neuromuscular junction. The serologic tests used for diagnosis include acetylcholine receptor and muscle specific receptor tyrosine kinase antibodies. Studies often have reported that patients with formal antibody are negative for the latter one. However, very limited studies have reported positive anti-muscle specific receptor tyrosine kinase antibody in a small percentage of patients with acetylcholine receptor antibody. Here, we reported a young woman who was diagnosed with MG and had a rapid and progressive course of the disease. She was seropositive for both acetylcholine receptor and muscle-specific receptor tyrosine kinase antibodies simultaneously. However, she discharged from the hospital with good condition after treatment.

Tacrolimus inhibits Th1 and Th17 responses in MuSK-antibody positive myasthenia gravis patients

Muscle specific tyrosine kinase antibody positive myasthenia gravis (MuSK- MG) is characterized by autoantibodies against the MuSK protein of the neuromuscular junction resulting in weakness of bulbar and proximal muscles. We previously demonstrated that patients with MuSK-MG have increased pro-inflammatory Th1 and Th17 responses. Tacrolimus, an immunosuppressant used in AChR-MG and transplantation patients, inhibits T cell responses through interference with IL-2 transcription. The therapeutic efficacy and immunological effect of tacrolimus in MuSK-MG is unclear. In the current study we examined the proliferation, phenotype and cytokine production of CD4+ and CD8+ T cells in peripheral blood mononuclear cells of MuSK-MG following a 3-day in vitro culture with or without tacrolimus. We determined that tacrolimus profoundly suppressed CD4 and CD8 T cell proliferation and significantly suppressed Th1 and Th17 responses, as demonstrated by a reduced frequency of IFN-γ, IL-2, and IL-17 producing CD4 T cells and reduced frequencies of IFN-γ and IL-2 producing CD8 T cells. Tacrolimus also inhibits pathogenic Th17 cells coproducing IL-17 and IFN-γ. In addition, tacrolimus suppressed follicular T helper cell (Tfh) and regulatory T helper cell (Treg) subsets. These findings provide preliminary support for tacrolimus as a potential alternative immunosuppressive therapy for MuSK-MG.

English

Myasthenia gravis is a neuro-muscular junction disorder characterized by skeletal muscle weakness and fatiguability. It is due to a decrease in the number of available acetylcholine receptors at the neuromuscular junction as a result of antibody mediated autoimmune attack. Weakness of muscles may involve cranial and somatic musculatures. Weakness resembling myasthenia gravis may occur in other conditions as a result of drug, endocrine disease of thyroid, certain malignancies, bacterial toxins and also by non-autoimmune mechanisms involving the neuromuscular junction. The weakness may involve all the skeletal muscles of the body but the distribution of weakness has a characteristic pattern and there is a diurnal variation of symptoms. If the weakness of respiratory muscles becomes so severe as to require respiratory assistance, then it is called myasthenic crisis. The myasthenia may be generalized one involving all the groups of muscles or it may involve the extra ocular muscles and facial muscles. Sometimes the bulbar muscles alone may be involved and the condition is called bulbar myasthenia gravis. In some of the patients, (anti-AchR) Acetyl choline receptor antibodies may be positive and in some it will be negative. In some of the patients, anti-muscle specific tyrosine kinase antibodies will be positive and negative in some of the patients. CONCLUSION : 1. In our study, the commonest age group of presentation of myasthenic crisis is the fourth decade (36%). 2. Male predominance (56%) was noted in our study. 3. The most common predisposing factor is the respiratory infection (28%). 4. In three patients, the presenting symptoms of myasthenia gravis was crisis itself. 5. The mean duration of onset of myasthenia gravis to the onset of crisis was 439.36 days. 6. The duration of myasthenia gravis does not influence the occurrence of myasthenic crisis. 7. Our patients presented with predominant bulbar symptoms with respiratory distress. 8. Ventilator associated pneumonia and other respiratory complications influenced the outcome of treatment of myasthenic crisis. 9. 32% of thymectomised patients had myasthenic crisis. 10. Higher age is a risk factor and younger age is a favourable factor for good outcome. 11. Duration of myasthenia gravis have no role on the outcome of crisis. 12. The better survival rate in ventilated patients outweigh the preventable ventilator related complications.

Thymolipoma-associated Myasthenia Gravis with High Titer of Anti-MuSKAb: A Case Report.

Myasthenia gravis (MG) is a neuromuscular junction disorder caused by pathogenic autoantibodies to some parts of the post-synaptic muscle endplates. About 85% of generalized MG patients have autoantibodies against post-synaptic acetyl-choline receptors (AChR). From the 10-15% of the remaining patients, 45-50% are positive for Muscle Specific Tyrosine Kinase-Antibody (MuSK-Ab). It is believed that the thymus has a critical role in the pathogenesis of the disease with AChR-Ab, specially in patients with thymic abnormalities. In contrast, the role of thymus gland in MG with anti-MuSK-Ab is not clearly obvious. Patients with this antibody virtually have normal or only minimal follicular hyperplastic thymus. The presence of anti-MuSK Ab in a thymolipomatous (an uncommon tumor of thymus) MG is an atypical and new finding of MG because of not only thymolipoma but the presence of anti-MuSK antibodies which makes this case different from the previous reports of the antibodies-associated MG. Here, we present a young woman with thymolipoma and MG (a very uncommon kind of tumor-associated MG) and high level of anti-MuSK-Ab.

Myasthenia gravis in South Trinidad.

There is no previous research on Myasthenia Gravis (MG) in Trinidad and Tobago. This study sought to determine the prevalence and to characterize MG in South Trinidad. A cross-sectional study was performed over 30 months in South Trinidad to identify, interview and statistically analyse data on MG cases. Among 36 prevalent patients, female:male ratio was 1.6:1. Estimated MG point prevalence in South Trinidad on March 31, 2010 was 78 per million. Mean age of prevalent patients was 50.5 years. Mean age of onset was 35 years. A higher prevalence was detected in Africans than East Indians (178 vs 68 per million; p = 0.003). Ocular and extremity muscle weakness were the most common initial symptoms. Autoimmune conditions (mainly thyroid disease) co-existed in 25.7%. Treatment involved pyridostigmine and/or immunosuppressants for all except two that went into remission with just steroids. Generalized MG occurred in 60%; 42.9% expressed social and/or professional handicap. One case with suggestive clinical features tested positive for muscle specific tyrosine kinase antibody. While many features of MG in South Trinidad were similar to international data, the unique, statistically significant higher prevalence in Africans than East Indians warrants further research, given the paucity of reports from Africa and India. Patients with MG suffered a diminished quality of life, necessitating improved health planning.