Myasthenia Gravis: Antibody Testing – Diagnosis

by Roy Strowd, MD

My Notes
  • Required.
Save Cancel
    Learning Material 2
    • PDF
      Slides Strowd Myasthenia Gravis.pdf
    • PDF
      Download Lecture Overview
    Report mistake

    00:01 So let's look a little bit more at the serologic testing for myasthenia gravis.

    00:05 We said that approximately 85 to 90% of myasthenics will be seropositive.

    00:09 They will have the presence of circulating antibodies.

    00:13 The most common antibody is the acetylcholine receptor antibody.

    00:17 And we can divide that antibody into three different types.

    00:20 There is a binding, blocking, and modulating acetylcholine receptor antibody.

    00:25 Let's look at what each of those antibodies does at the neuromuscular junction.

    00:30 The binding antibody activates complement.

    00:33 An activation of complement leads to loss of postsynaptic acetylcholine receptors.

    00:37 You don't have as many acetylcholine receptors, and so you can't drive as much end-plate potential.

    00:44 The blocking antibodies impair binding of acetylcholine.

    00:48 They get in the way.

    00:49 They obstruct the binding of acetylcholine to its postsynaptic receptor leading to poor muscle contraction.

    00:56 And the modulating antibodies result in what's called antigenic modulation.

    01:02 There's receptor endocytosis less receptors are available on the postsynaptic membrane.

    01:07 and this results in clinical symptoms.

    01:10 And the degree of antibody modulation correlates with the clinical severity of disease.

    01:16 So let's look at each of these specifically.

    01:19 What happens in the case of those binding antibodies? Acetylcholine receptor binding antibodies bind to the acetylcholine receptor.

    01:27 It sits on the postsynaptic terminus on the muscle and drives muscles to contract.

    01:34 When that binding antibody binds to acetylcholine or multiple acetylcholine receptors together, we see that complement is activated.

    01:43 As a result of complement activation, the postsynaptic acetylcholine receptors are moved into the cell and degraded.

    01:50 And so the end result is there are less acetylcholine receptors on the postsynaptic terminus on the muscle.

    01:56 And there is less potential to drive an end-plate potential.

    01:59 Less ability to activate that muscle.

    02:03 What about the blocking antibodies? How do those work? Well, blocking antibodies are competitive antagonist of the postsynaptic acetylcholine receptor.

    02:12 They find their way into the synaptic cleft, they bind to the acetylcholine receptor and prevent acetylcholine from binding to the acetylcholine receptor.

    02:21 And therefore, they prevent end-plate potential activation and prevent muscle contraction.

    02:27 And we can see that here auto antibodies to the acetylcholine receptor are binding and preventing muscle activation and contraction.

    02:36 What about the modulating antibodies? How did they work? What is antigenic modulation? Well, here we see that signal-induced down regulation of protein expression occurs.

    02:47 These antibodies bind to the acetylcholine receptor.

    02:50 As a result of that binding, we see cross-linking of the acetylcholine receptors on the muscle membrane.

    02:56 Those cross linked acetylcholine receptors are internalized by the cell they're recognized as abnormal and they're internalized and thus degraded.

    03:05 And so again, you see a downregulation of the number of acetylcholine receptors that are on the muscle membrane.

    03:12 And it takes much, much more activation of the nerve and the neuromuscular junction to drive muscle contraction.

    About the Lecture

    The lecture Myasthenia Gravis: Antibody Testing – Diagnosis by Roy Strowd, MD is from the course Disorders of the Neuromuscular Junctions.

    Included Quiz Questions

    1. Attachment of anti-AChR antibodies to the AChR leads to complement activation and ultimate endocytosis and degradation of AChR.
    2. Antibodies act as competitive antagonists to the post-synaptic AChR.
    3. Antibodies lead to signal-induced down-regulation of protein expression.
    4. Cross-linking of AChR after antibody binding leads to internalization of the AChR in a complement independent manner.
    5. Binding AChR antibodies enter the synaptic cleft and act as competitive agonists to the post-synaptic AChR.
    1. Impairs binding of ACh, leading to poor muscle contraction
    2. Cross-linking of AChR leading to complement activation and degradation of receptors
    3. Antigenic modulation occurs, leading to receptor endocytosis.
    4. Acetylcholinesterase is inhibited.
    5. The anti-AChR blocking Ab acts an indirect agonist on the AChR.

    Author of lecture Myasthenia Gravis: Antibody Testing – Diagnosis

     Roy Strowd, MD

    Roy Strowd, MD

    Customer reviews

    5,0 of 5 stars
    5 Stars
    4 Stars
    3 Stars
    2 Stars
    1  Star