Type of test :  Blood

 Normal findings

 ACh receptor (muscle) binding antibodies: ≤ 0.02 nmol/L ACh receptor (muscle) modulating antibodies: 0%-20% (reported as % loss of AChR)

 Striational (striated muscle) antibodies: < 1:60

 Test explanation and related physiology

       These autoantibodies may cause blocks in neuromuscular transmission by interfering with the binding of acetylcholine (ACh) to ACh receptor (AChR) sites on the muscle membrane, thereby preventing muscle contraction. This phenomenon characterizes  myasthenia gravis (MG). Antibodies to AChR occur in more than 85% of patients with acquired MG. Lower levels are seen in patients with ocular MG only. The presence of these antibodies is virtually diagnostic of MG, but a negative test result does not exclude the disease. The measured titers do not correspond well with the severity of MG in different patients. In an individual patient, however, antibody levels are particularly useful in monitoring response to therapy. As the patient improves, anti body titers decrease. In adults with MG, there is at least a 20% occurrence of thymoma or other neoplasm. Neoplasms are an endogenous source of the antigens driving production of AChR autoantibodies.

 Several AChR antibodies can be associated with MG. The AChR-binding antibody can activate complement and lead to loss of AChR. Binding AChR antibodies are highly specific for myasthenia gravis. There are virtually no false-positive results. Binding antibody studies are sufficient in most circumstances to diagnose MG. The other antibodies may be helpful if a possible false-positive binding antibody result is suspected or if the binding antibody is negative but the disease is still strongly suspected clinicially.

 Lipoprotein receptor-related protein 4 (LRP4) is another autoantibody that activates MuSK, and AChR clustering and neuromuscular junction formation have been found in approximately 10% of patients who are seronegative. The AChR-modulating antibody causes receptor endocytosis, resulting in loss of AChR expression, which correlates most closely with clinical severity of disease. It is the most sensitive test. A positive modulating antibody test result may indicate subclinical MG, contraindicating the use of curare like drugs during surgery. The AChR-blocking antibody may impair binding of ACh to the receptor, leading to poor muscle contraction. It is the least sensitive test (positive in only 61% of patients with MG).

Antistriated muscle antibody (striated muscle antibody, IgG) titers greater than or equal to 1:80 are suggestive of myasthenia. This antibody is detectable in 30% to 40% of anti-AChR negative patients (particularly those with bulbar symptoms only). However, striated muscle antibody can be found in rheumatic fever, myocardial infarction, and a variety of postcardiotomy states. Muscle-specific tyrosine kinase (MuSK-Ab) is an antibody against a receptor-associated protein. This antibody is mostly positive in generalized MG.

Interfering factors

 • False-positive results may occur in patients with amyotrophic lateral sclerosis who have been treated with cobra venom.

 • False-positive results may be seen in patients with penicillamine induced or Lambert-Eaton myasthenic syndrome.

 • Patients with autoimmune liver disease may have elevated results.

* Drugs that may cause increased levels include muscle paralytic medicines (succinylcholine) and snake venom.

* Immunosuppressive drugs may suppress the formation of these antibodies in patients with subclinical MG.

 Procedure and patient care

 • See inside front cover for Routine Blood Testing.

 • Fasting: no

 • Blood tube commonly used: red

Abnormal findings

Increased titer levels

- Myasthenia gravis

- Ocular myasthenia gravis

- Thymoma