The cause of<unk>  is unknown.<unk>  likely results from the interaction of a number of genetic and environmental factors. There are two major theories about how sIBM is caused. One hypothesis suggests that the inflammation-immune reaction, caused by an unknown trigger – likely an undiscovered virus or an autoimmune disorder – is the primary cause of sIBM and that the degeneration of muscle fibers and protein abnormalities are secondary features. Despite the arguments "in favor of an adaptive immune response in sIBM, a purely autoimmune hypothesis for sIBM is untenable because of the disease's resistance to most immunotherapy." The second school of thought advocates the theory that sIBM is a degenerative disorder related to aging of the muscle fibers and that abnormal, potentially pathogenic protein accumulations in myofibrils play a key causative role in sIBM (apparently before the immune system comes into play). This hypothesis emphasizes the abnormal intracellular accumulation of many proteins, protein aggregation and misfolding, proteosome inhibition, and endoplasmic reticulum (ER) stress. One review discusses the "limitations in the beta-amyloid-mediated theory of<unk>  myofiber injury." Dalakas (2006) suggested that a chain of events causes<unk>  – some sort of virus, likely a retrovirus, triggers the cloning of T cells. These T cells appear to be driven by specific antigens to invade muscle fibers. In people with sIBM, the muscle cells display "flags" telling the immune system that they are infected or damaged (the muscles ubiquitously express MHC class I antigens) and this immune process leads to the death of muscle cells. The chronic stimulation of these antigens also causes stress inside the muscle cell in the endoplasmic reticulum (ER) and this ER stress may be enough to cause a self-sustaining T cell response (even after a virus has dissipated). In addition, this ER stress may cause the misfolding of protein. The ER is in charge of processing and folding molecules carrying antigens. In<unk> , muscle fibers are overloaded with these major histocompatibility complex (MHC) molecules that carry the antigen protein pieces, leading to more ER stress and more protein misfolding. A self-sustaining T cell response would make sIBM a type of autoimmune disorder. When studied carefully, it has not been possible to detect an ongoing viral infection in the muscles. One theory is that a chronic viral infection might be the initial triggering factor setting<unk>  in motion. There have been a handful of<unk>  cases – approximately 15 – that have shown clear evidence of a virus called HTLV-1. The HTLV-1 virus can cause leukemia, but in most cases lies dormant and most people end up being lifelong carriers of the virus. One review says that the best evidence points towards a connection with some type of retrovirus and that a retroviral infection combined with immune recognition of the retrovirus is enough to trigger the inflammation process. * amyloid protein * The hypothesis that beta amyloid protein is key to<unk>  has been supported in a mouse model using an Aβ vaccine that was found to be effective against<unk>  in mouse models. Although this vaccine is likely, not safe for human use, it still shows that attacking Aβ has efficacy in mice against<unk> . * Following up on earlier leads, the Greenberg group report finding that the protein TDP-43 is a very prominent and highly sensitive and specific feature of<unk> . This protein is normally found within the nucleus but in<unk>  is found in the cytoplasm of the cell. This important advance should help develop a new screening technique for<unk>  and may provide clues in terms of a therapeutic approach Genetics sIBM is not inherited and is not passed on to the children of<unk>  patients. There are genetic features that do not directly cause<unk>  but that appear to predispose a person to getting<unk>  – having this particular combination of genes increases one's susceptibility to getting<unk> . Some 67% of<unk>  patients have a particular combination of human leukocyte antigen genes in a section of the 8.1 ancestral haplotype in the center of the MHC class II region. sIBM is not passed on from generation to generation, although the susceptibility region of genes may be. There are also several rare forms of hereditary inclusion<unk>  myopathy that are linked to specific genetic defects and that are passed on from generation to generation. Since these forms do not show features of muscle inflammation, they are classified as myopathies rather than forms of myositis. Because they do not display inflammation as a primary symptom, they may in fact be similar, but different diseases to sporadic<unk> . There are several different types, each inherited in different ways. See hereditary inclusion<unk>  myopathy. A 2007 review concluded there is no indication that the genes responsible for the familial or hereditary conditions are involved in sIBM.
Inclusion body myositis
Dermatomyositis
Nemaline myopathy
Polymyositis
Dermatopolymyositis
Centronuclear myopathy
Hereditary inclusion body myopathy
Brody myopathy