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Acetylcholine receptor (AChR) antibodies are autoantibodies that target the acetylcholine receptors at the neuromuscular junction. These antibodies are primarily associated with Myasthenia Gravis (MG), an autoimmune neuromuscular disorder characterized by fluctuating muscle weakness and fatigue. The presence of AChR antibodies disrupts normal neuromuscular transmission, leading to the characteristic symptoms of MG.

Pathophysiology of Myasthenia Gravis and antibodies

• Blocking: AChR antibodies bind to the acetylcholine receptors on the postsynaptic membrane, preventing acetylcholine from binding and activating the receptors.
• Internalization and Degradation: The binding of AChR antibodies leads to the internalization and degradation of acetylcholine receptors, reducing their availability on the muscle cell surface.
• Complement Activation: AChR antibodies can activate the complement system, leading to the destruction of the postsynaptic membrane and further loss of acetylcholine receptors.

Clinical Significance

• Ocular Symptoms: Ptosis (drooping of the eyelids), diplopia (double vision).
• Bulbar Symptoms: Dysphagia (difficulty swallowing), dysarthria (slurred speech).
• Generalized Muscle Weakness: Fatigue, weakness which may worsen with activity and improve with rest.
• Respiratory Symptoms: myasthenic crisis with respiratory failure.

Types of Acetylcholine Receptor Antibodies

• Binding Antibodies: most common type in about 85% of patients with generalized MG. They bind directly to the acetylcholine receptors and disrupt their function.
• Blocking Antibodies: block the binding of acetylcholine to its receptor, further inhibiting neuromuscular transmission.
• Modulating Antibodies: cause the Ach receptors to be internalized and degraded, reducing their number on the muscle cell surface.

Investigations

• Serological Testing: Blood tests to detect AChR antibodies, including binding, blocking, and modulating antibodies. The presence of these antibodies supports the diagnosis of MG.
• Electrophysiological Studies: Repetitive nerve stimulation and single-fiber electromyography (EMG) can assess neuromuscular transmission and help confirm the diagnosis.
• Imaging Studies: A chest CT or MRI may be performed to check for a thymoma, a tumour of the thymus gland that is often associated with MG.
• Clinical Examination: Assessment of muscle strength, particularly in the eyes, face, and limbs, can provide clues to the presence of MG.

Management

• Anticholinesterase Medications: e.g. pyridostigmine increases Ach at the neuromuscular junction, improving muscle strength.
• Immunosuppressive Therapy: Corticosteroids, azathioprine, mycophenolate help reduce the production of autoantibodies.
• Plasmapheresis and Intravenous Immunoglobulin (IVIG): reduce the levels of circulating antibodies, particularly during a myasthenic crisis.
• Thymectomy: may be beneficial, especially in patients with a thymoma or generalized MG, as it can lead to long-term improvement or remission.

Sample

• Sample Requirements: Adult 5ml Gold-top SST tube or 3.5ml Rust-top gel tube