Antineutrophil Cytoplasmic Antibodies and Cell-mediated Vasculitis – Vasculitis

by Richard Mitchell, MD

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    00:01 So, immune complex mediated arteritis include things like polyarteritis nodosa.

    00:08 That's in the medium to large size vessels all the way over on the left-hand side.

    00:13 Small vessel vasculitis that has a similar pathogenesis, etiology, include things like a lupus vasculitis, systemic lupus erythematous, SLE vasculitis, or IGA associated vasculitis that is Henoch-Schonlein purpura, or other sorts of vasculitides due to antibodies binding.

    00:35 In that case, Goodpasture's disease where the antibodies are actually directed against a component of the basement membrane.

    00:43 Okay, so those are examples.

    00:44 We'll spend more time talking about the specifics at the back end of this talk.

    00:49 All right, a third kind of pathogenic mechanism to think about.

    00:54 So, we've had antiendothelial cell antibody, we had immune complex deposition.

    00:58 There's an entity called antineutrophil cytoplasmic antibodies, so called ANCA, antineutrophil cytoplasmic antibodies.

    01:08 These ANCA antibodies can be elaborated after a variety of infections or other triggers.

    01:14 And what they do is bind to cytoplasmic components of neutrophils.

    01:20 In particular, proteinase 3, PR3, and myeloperoxidase.

    01:25 And you're thinking, okay, now, these are normally cytoplasmic antigens.

    01:29 How are they getting on the surface? Well, when a neutrophil gets activated, it can actually have translocation of a number of proteins to the cell surface.

    01:38 Now, we have an antibody against PR3 or antibody against myeloperoxidase that's on the surface of a neutrophil, and it come along with an antibody and bind to it, wow.

    01:48 Now, I'm going to really turn on that neutrophil.

    01:52 We're going to activate complement, but we're also going to have Fc receptor interactions even on the same cell.

    01:59 And so, that's going to drive a pretty profound inflammatory response.

    02:04 So, again, we have some sort of trigger.

    02:07 We develop antibodies against PR3 or myeloperoxidase.

    02:10 Those bind to neutrophils. The neutrophils also - as they translocate these contents to the surface, can also deposit them on various other surfaces such as the endothelium.

    02:23 So, we can have now antibodies bound to the endothelium as well, because of the PR3 or myeloperoxidase that have glommed onto the endothelium.

    02:32 In any event, we're going to get activation of the neutrophils.

    02:34 We're going to get activation and injury of the endothelial cells as a result of the antibody binding.

    02:40 And then, we're off and running. Same process.

    02:43 Complement fragments, Fc receptor bearing cells, et cetera, giving rise to a vasculitis.

    02:49 So, examples of the ANCA associated vasculitides include now vasculitis without asthma or granulomas.

    02:59 That's microscopic polyangiitis, kind of in the middle top of your screen.

    03:03 There are granulomas without asthma or Wegener's granulomatosis.

    03:08 And then, there's vasculitis associated with eosinophils, asthma, and granulomas, otherwise known as Chrug-Strauss syndrome.

    03:16 So, that's an example of ANCA associated vasculitides.

    03:21 Okay, we built up our repertoire. There's one more.

    03:24 So, we've had antiendothelial cell antibodies, immune complex antibodies, ANCA antibodies.

    03:31 What about just a typical cell mediated vasculitis? Well, indeed, there are cell mediated injury of vessel walls just like everything else.

    03:40 So, lymphocytes can be targeted to antigens that are expressed in various parts of the vessel wall from endothelium to smooth muscle cells and even adventitial cells.

    03:50 When those lymphocytes identify their particular antigen, so they get activated, will recruit and activate additional mononuclear cells, monocytes, and macrophages.

    04:01 And then, we're off and running.

    04:03 They will elaborate mediators that will cause the formation of granulomas.

    04:08 Activated nodules epithelioid macrophages, but also profoundly activate the lymphocytes and macrophages that are there.

    04:16 Elaborating cytokines, reactive oxygen species, proteases, et cetera, that cause damage to the vessel wall. Boom.

    04:23 Vessel wall is damaged, and now we have the same process. We have a vasculitis.

    04:28 Now, due to T cells, T lymphocytes that are directed against antigens of the vessel wall, an example of this, over on the left-hand side at the bottom, are granulomatous diseases such as Takayasu's arteritis and giant cell arteritis, and we'll talk a little bit more in specifics later.

    About the Lecture

    The lecture Antineutrophil Cytoplasmic Antibodies and Cell-mediated Vasculitis – Vasculitis by Richard Mitchell, MD is from the course Vasculitis.

    Included Quiz Questions

    1. Myeloperoxidase
    2. Cathepsin K
    3. Proteinase 13
    4. Elastin
    5. Lactoferrin 13
    1. Multinucleated giant cells
    2. Contraction band necrosis
    3. Rosette
    4. Pseudorosette
    5. Platelet-fibrin emboli

    Author of lecture Antineutrophil Cytoplasmic Antibodies and Cell-mediated Vasculitis – Vasculitis

     Richard Mitchell, MD

    Richard Mitchell, MD

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