Inclusion body myositis (IBM) is a common inflammatory myopathy of the elderly. It is characterized by slowly progressive weakness that leads to difficulty using the arms and legs, impaired ambulation and swallowing. None of the known immune therapies have proven to be effective for its treatment. In the absence of serum biomarkers for the disease, diagnosis relies on the performance of muscle biopsies. Despite this, IBM may still be misdiagnosed with other inflammatory myopathies, leading to months of unnecessary treatment with glucocorticoid drugs or immunosuppressive agents with significant side effects. While not common, it may also be misdiagnosed for amyotrophic lateral sclerosis (ALS), with major emotional and psychological consequences. While IBM is a slowly progressive muscle disease with normal life expectancy, ALS is a rapidly progressive motor neuron disorder that will lead to mechanical ventilation and carries a median survival time of 2-4 years. Developing a reliable serum biomarker for IBM will not only be extremely valuable in avoiding misdiagnosis and its occasional devastating consequences, but may circumvent the need for painful and invasive muscle biopsies. In pursuing a serum based diagnostic assay for IBM we have identified a circulating antibody in the blood of IBM patients that is 100% specific and 52% sensitive for this disease among a small number of samples studied. Based on this finding, we propose a project to further characterize the nature of this reactivity by (1) determining its sensitivity and specificity in a larger number of IBM and control subjects, in particular those that can be misdiagnosed with IBM, (2) describe whether or not these sera have specific staining patterns on muscle tissue biopsy slides and (3) whether the presence of reactivity or staining pattern signifies a particular subgroup of IBM patients with therapeutic and prognostic implications. We plan to pursue our goals by first identifying subjects with IBM, inflammatory and non-inflammatory myopathies as well as ALS, and collect their blood samples. We will then examine their sera for reactivity against this 43 kDa muscle protein, using western blots, and also determine tissue staining patterns for those that prove to be reactive. Finally, we will compare detailed demographic and clinical data between reactive and non-reactive IBM subjects to determine if we can identify disease subgroups.
Inclusion body myositis is the most common inflammatory myopathy of the elderly that may be clinically mistaken with other forms of muscle disease and even amyotrophic lateral sclerosis (ALS). Since differentiation requires performance of painful muscle biopsies, identification of serum markers and development of diagnostic bioassays for the disorder would be of great value. In addition, identifying disease subgroups based on these markers may have prognostic and therapeutic implications for IBM patients.
|Paganoni, Sabrina; Quinn, Colin; Salajegheh, Mohammad Kian (2014) Clinical reasoning: a 20-year-old woman with rapidly progressive weakness. Neurology 82:e200-4|