Apoptosis in polymyositis

Polymyositis is traditionally seen as an inflammatory myopathy mediated by cytotoxic T cells (Hengstman December 2004). [1]

Interestingly, this destruction by t-cells is not as a normal part of cell apoptosis. "In the inflammatory myopathies, T cell inflammation is not cleared by apoptosis and affected muscle fibers do not die by apoptosis." (Schneider, Gold 1996). [2]

I take this to mean that cells do not die by normal programmed cell death, nor does the body deliberately kill them as a way of stopping the disease. Nor, apparently does the death of a diseased muscle fiber relieve the process.

T cells may have direct and indirect toxic effects on muscle fibres, causing muscle fiber necrosis and muscle weakness, but the target of the immune reaction is not known. A newly identified T cell subset, CD28^null T cells, may have cytotoxic effects in the CD4⁺ and CD8⁺ T cell phenotype. These cells are apoptosis resistant and may contribute to treatment resistance. (3) Such information will be important for the development of new therapies.(3)

 

Non-immune pathway

 Degeneration and necrosis are characteristic histopathologic features of myositis, classic apoptosis features are often not detected. Several studies have suggested that autophagy may be responsible for muscle fiber death. TNF-α-related apoptosis-inducing ligand (TRAIL) protein, an inducer of autophagic cell death, is overexpressed particularly in atrophic and regenerating areas of the muscle in both PM and DM muscle. (4) 

 Recent literature indicates that tumor necrosis factor-alpha-related apoptosis inducing ligand (TRAIL) may induce both NFκB (nuclear factor kappa-light chain enhancer of activated B cells) activation and autophagic cell death in other systems. Several studies demonstrate that TRAIL is expressed in myositis muscle and may mediate both activation of NFκB and autophagic cell death in myositis. Thus, this non-immune pathway may be an attractive target for therapeutic intervention in myositis. (5)

Article contributed by Dr. JOSE PEREIRA, MD

Footnotes:

1.  Hengstman G, van Engelen B. Polymyositis, invasion of non-necrotic muscle fibres, and the art of repetition. BMJ, 329.7480.1464, 2004 as found at VIEW

2.  Schneider C, Gold R. MHC class 1-midiated cytotoxicity does not induce apoptosiss in muscle fibres nor in inflammatory Tcells: studies in patients with polymyositis, dermatomyocitis, and inclusion body myositis. J Neuropathol Exp Neurol , 55(12): 1205-9, 1996 as found at VIEW

3. Paulius V. B-cell survival factors in autoimmune rheumatic disordersTherapeutic Advances in Musculoskeletal Disease (2015) 7 (4): 122-151. http://rheumatology.oxfordjournals.org/content/early/2013/08/22/rheumatology.ket279.short

4. Arash H L. Polymyositis and Dermatomyositis: Novel Insights into the Pathogenesis and Potential Therapeutic Targets. Division of Rheumatology, Johns Hopkins University School of Medicine. Published on june 26, 2015.http://www.discoverymedicine.com/Arash-H-Lahouti/2015/06/polymyositis-and-dermatomyositis-novel-insights-into-the-pathogenesis-and-potential-therapeutic-targets/

5. Alger HM, . The role of tumor necrosis factor-α-related apoptosis-inducing ligand (TRAIL) in mediating autophagy in myositis skeletal muscle: A potential non-immune mechanism of muscle damage. Arthritis and rheumatism. 2011;63(11):3448-3457. doi:10.1002/art.30530. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3203318/

 

 

Footnotes:

1. Hengstman G, van Engelen B. Polymyositis, invasion of non-necrotic muscle fibres, and the art of repetition. BMJ, 329.7480.1464, 2004 as found at VIEW

2. Schneider C, Gold R. MHC class 1-midiated cytotoxicity does not induce apoptosiss in muscle fibres nor in inflammatory Tcells: studies in patients with polymyositis, dermatomyocitis, and inclusion body myositis. J Neuropathol Exp Neurol , 55(12): 1205-9, 1996 as found at VIEW

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