Coexistent of muscle specific tyrosine kinase and acetylcholine receptor antibodies in a myasthenia gravis patient

Hamid Suhail¹, Subbiah Vivekanandhan², Sumit Singh¹, Madhuri Behari¹,  
¹ Department of Neurology, All India Institute of Medical Sciences, New Delhi, India
² Department of Neurobiochemistry, All India Institute of Medical Sciences, New Delhi, India

Correspondence Address:
Madhuri Behari
Department of Neurology, All India Institute of Medical Sciences, New Delhi
India

Full Text

Sir,

Myasthenia gravis (MG) is an autoimmune disorder with approximately 80-85% expressing antibodies against nicotinic acetylcholine receptors (nAChR-). [1] Of the seronegative MG patients, 40 -70% are positive for muscle specific tyrosine kinase antibodies (MuSK-Ab). [2] MuSK-Ab is usually positive in MG patients who are negative for AChR-Ab with progressive course, severe oculo-bulbar involvement, neck drop and respiratory muscle weakness. [3] Presence of both AChR-Ab and MuSK-Ab in the same MG patient is a very rare phenomenon.

A 31year-old female patient was first seen at another hospital in 2002, with 2 years history of intermittent bilateral ptosis, diplopia, proximal muscle weakness, easy fatigability, dysphagia, breathlessness, nasal regurgitation, slurred speech with nasal tone and neck muscle weakness. There was no family history of similar illness. The patient also had hypothyroidism and was on supplemental therapy. Repetitive nerve stimulation test (RNST) revealed decrement response but neostigmine test was negative. AChR and MuSK antibodies were not tested at that stage. Computerized tomographic scan of thorax showed evidence of thymic hyperplasia and thymectomy was done in 2002. The histopathology of thymus confirmed thymic hyperplasia. After thymectomy, the patient showed dramatic improvement in all the clinical symptoms except speech which continued to be slurred and nasal. She remained in remission for 6 years. In 2008, she presented to our neurology clinic facility with recurrence of symptoms, ptosis and diplopia. AChR and MuSK antibodies were tested on two separate occasions by radioimmunoassay method (RIA) using radio-receptor assay kit as per manufacturer's protocol, and she was detected positive for both the antibodies. [4] Her AChR-Ab titer was 2.47 and 1.45 nmol/L and MuSK-Ab titer was 2.23 and 1.75 nmol/L. She was treated with pyridostigmine 60 mg thrice daily with a satisfactory response.

This report presents a very rare patient of MG, who was positive for both AChR and MuSK antibodies. This is the only case in our records of more than 400 MG patients who tested positive for both AChR-Ab and MuSK-Ab. Literature survey revealed one such report who was positive for both AChR-Ab and MuSK-Ab, from UK by Al Saleh and Cariga in 2007. [5] Ohta et al. in 2004 reported MuSK-Abs in AChR-Ab seropositive MG patients, but later they withdrew the report because what they initially believed to be MuSK-Abs turned out to be antibodies to alkaline phosphatase. [6] Saulat et al. reported a case of MG, who was AChR-Ab positive and MuSK-Ab negative before thymectomy, but converted to MuSK-Ab positive and AChR-Ab negative after thymectomy. [7] The authors attributed this to "epitope spreading". Subsequent occurrence of both AChR-Ab and MuSK-Ab with disease relapse is considered to be due to epitope spreading, suggesting the spread of immunologic attack against AChR to include MuSK, with an altered pattern of autoimmune cross reactivity. [8] In experimental models of autoimmune diseases, the phenomenon of epitope spreading is well known. [9] However, in our case, it is difficult to say that this phenomenon of epitope spreading is applicable, since her earlier antibody status is not known. The first time we saw this patient was when she was almost 8 years into illness and after thymectomy with recurrence of symptoms. There is a small probability that relapse of disease may be due to reactivation and proliferation of lymphocytes in germinal hyperplasia after thymectomy. These autoreactive lymphocyte cells might have induced a distinct antibody response and the possibility of cross reacting epitopes happened. Coexistence of MuSK-Ab and AChR-Ab positivity in an MG patient suggests more severe and extensive range of clinical presentation. Additionally, AChR-Ab positive patients with MG should also be considered for MuSK antibody test for better prognosis and treatment.

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