There have been a handful of IBM 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 IBM has been supported in a mouse model using an Aβ vaccine that was found to be effective against inclusion body myositis in mouse models. Although this vaccine is likely, not safe for human use, it still shows that attacking Aβ has efficacy in mice against IBM. 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 IBM. This protein is normally found within the nucleus but in IBM is found in the cytoplasm of the cell. This important advance should help develop a new screening technique for IBM and may provide clues in terms of a therapeutic approach

Genetics
sIBM is not inherited and is not passed on to the children of IBM patients. There are genetic features that do not directly cause IBM but that appear to predispose a person to getting IBM – having this particular combination of genes increases ones susceptibility to getting IBM.
sIBM is a challenge to the pathologist and even with a biopsy, diagnosis can be ambiguous.A diagnosis of inclusion body myositis was historically dependent on muscle biopsy results. Antibodies to cytoplasmic 5-nucleotidase (cN1A; NT5C1A) have been strongly associated with the condition. However, other inflammatory conditions, such as lupus, can have a positive anti-NT5C1A. As of 2019, it remains to be established whether a positive anti-NT5C1A antibody test can make muscle biopsy unneeded. Muscle imaging can help establish the pattern of muscle involvement and selection of a biopsy site. Differential diagnosis
IBM is often initially misdiagnosed as polymyositis. A course of prednisone is typically completed with no improvement and eventually, sIBM is confirmed. sIBM weakness comes on over months or years and progresses steadily, whereas polymyositis has an onset of weeks or months. Muscular dystrophy (e.g. limb girdle muscular dystrophy) must be considered as well. sIBM can be mistaken for physical deconditioning.Hereditary myopathies can mimic sIBM, both in signs and symptoms and in the appearance of muscle biopsies. A small percentage of those initially diagnosed with sIBM are later found to have pathogenic mutations in the genes VCP and SQSTM1, which are known to cause hIBM.IBM has a distinctive pattern of muscle involvement that distinguishes it among inflammatory myopathies. Characteristic of IBM is weakness of finger flexion, knee extension, and ankle dorsiflexion. Other inflammatory myopathies cause a proximal muscle weakness pattern, such as weakness of hip flexion, abduction, and extension, as well as shoulder abduction. IBM and other inflammatory myopathies both cause bicep/tricep weakness.