Myasthenia Gravis: Antibody Testing – Diagnosis

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.