Summary of Dermatomyositis
Transcript for Dermatomyositis
Content Reviewers:Rishi Desai, MD, MPH, Yifan Xiao, MD, Justin Ling, MD, MS, Tanner Marshall, MS, Marisa Pedron
In dermatomyositis, “-itis” refers to inflammation, “myos-“ to the muscles and “dermato-“ to the skin, so dermatomyositis is an inflammatory disorder which involves both the skin and the muscles.
Dermatomyositis is considered to be an autoimmune disease, meaning that the immune system has gone rogue and started attacking its own muscles and skin.
Okay, normally, the cells of the immune system are always hanging around, ready and excited to spot and fight against anything foreign that could cause harm inside the body.
B- lymphocytes produce antibodies against a specific part of these foreign pathogens, called antigen.
The tips of these antibodies strongly binds to this antigen, while the base of the antibody, called the constant region, gets recognized by complement proteins.
These complement proteins are a group of small proteins made by the liver that work together.
One complement protein cuts or cleaves the next one, activating it and creating an enzymatic cascade.
This process gets started with C1, the first of the complement proteins, which binds to the Fc, or the constant region of two antibody attached to the pathogen.
C1 then cleaves C2 and C4.
Portions of the C2 and C4 binds to the antigen and form an enzymatic complex that cleaves C3 into two portions, C3a and C3b.
C3b joins the enzymatic complex and then the complex is able to cleave C5 into two portions, C5a and C5b portion.
C5a and C3a float off into the blood where they attract other cells of the immune system to the affected area.
Meanwhile, C5b, C6, C7, C8 and multiple C9 proteins, come together on the surface of the pathogen to form the membrane attack complex or MAC.
The MAC attacks pathogenic cells, such as bacteria, by creating a channel in the cell membrane.
Because cells have more solutes in them than the outside environment, water flows into the cell by the process of osmosis, and that causes the cell to swell up and burst, which is called cell lysis.
In dermatomyositis, immune cells confuse normal muscle and skin proteins with foreign antigens.
This process is called molecular mimicry because from the perspective of the immune cells, a host protein is mimicking a foreign or tumor protein.
When normal proteins in our body trigger an immune response, that protein is called an autoantigen.
These autoantigens get picked up by B- lymphocytes, which begin producing antibodies against them.
In dermatomyositis, the autoantigens are usually found in various spots, like the endothelial cells lining the capillaries in muscle and skin cells, as well as soluble antigens coming from the nucleus or cytoplasm of destroyed muscle cells and skin cells.
So, in the first case, autoantibodies attach to the endothelial cells lining the capillaries near the perimysium, which is a sheath of connective tissue around bundles of muscle fibers.
Upon binding, these antibodies activate the complement cascade, leading to formation of the membrane attack complex which causes the endothelial cells to lyse.
The complement proteins also attract more inflammatory cells, like macrophages, to the area.