Immune Abnormalities in Sporadic Inclusion Body Myositis
Condition: Sporadic; Inclusion Body; Myositis
MeSH terms: Myositis; Myositis, Inclusion Body
Study type: Observational

Summary: 
      This study will examine the abnormal immune response in patients with sporadic inclusion body
      myositis (s-IBM)-the most common inflammatory muscle disease in people over the age of 50.
      s-IBM progresses steadily and may lead to severe weakness and wasting of arm and leg muscles.
      Patients may become unable to perform daily living activities and be confined to wheelchairs.
      s-IBM is thought to be an autoimmune disease, in which the body's own immune system attacks
      healthy muscles. This study will explore the causes of the muscle tissue inflammation that is
      responsible for destruction of muscle fibers and weakness in this disease. Information from
      the study may help in the development of an effective treatment for this disease.

      Patients with s-IBM may be eligible for this study. Those who are unable to travel or who
      have severe cardiovascular, renal or other end-stage organ disease will be excluded.
      Candidates will be screened for eligibility with a medical history and physical and
      neurological examinations.

      Participants will be seen at the NIH Clinical Center every six months over a 12-month period
      (visits at enrollment, 6 months and 12 months) either on an inpatient or outpatient basis,
      depending on their disease severity. Each 2- to 3-day visit will involve the following tests
      and evaluations:

        -  Blood samples for routine laboratory tests are collected at every visit. Additional
           blood for research studies is collected at 12 months.

        -  Quantitative muscle strength testing is done at every visit. The patient pulls against
           straps connected to dynamometers (devices that measure muscle power) to evaluate
           strength of the main muscle groups in the arms and legs.

        -  Lymphapheresis is done at enrollment and at 12 months. This is a procedure for
           collecting quantities of lymphocytes (white blood cells that are an important part of
           the immune system). Blood is collected through a needle placed in an arm vein and
           circulated through a machine that spins it, separating it into its components. The
           lymphocytes are removed and the rest of the blood (red cells, platelets and plasma) is
           returned to the body through the same needle or another needle placed in the other arm.

        -  Electrophysiologic studies (electromyography and nerve conduction testing) are done at
           enrollment and 12 months. Electromyography evaluates the electrical activity of muscles.
           A small needle is inserted into the muscle and the patient is asked to relax or to
           contract the muscle. For nerve conduction testing, nerves are stimulated by electrodes
           (small wires taped to the skin over the muscle).

        -  Muscle biopsy is done at enrollment and 12 months. A sample of muscle tissue (about the
           size of a lima bean) from an arm or leg is surgically removed to confirm the diagnosis
           of s-IBM and for analysis of proteins involved in the muscle inflammation process. A
           local anesthetic is used to numb the area before the surgery and the wound is closed
           with stitches.
    

Detailed description: 
      Sporadic Inclusion Body Myositis (s-IBM) is the most common acquired myopathy above the age
      of 50 years. It is a disabling disease that leads to wheelchair confinement. The cause is
      unknown but autoimmune mechanisms have been implicated. The primary goal of the study is to
      search for candidate autoantigen(s) that drive the autoimmune response and identify candidate
      pathogenic T-cell epitopes among the endomysial T-cells extracted from the patients' muscle
      biopsies. It is anticipated that the search for the antigens implicated in the clonal
      expansion of endomysial T-cells over time will elucidate the autoimmune pathogenesis of the
      disease and lead to the development of antigen-specific immunomodulatory therapeutic
      strategies. This is an investigative study intended to better define the pathogenesis of
      s-IBM. No new therapy will be provided except of standard care.
    

Keywords: T Cell; IBM; Inflammatory Myopathies; Antigenic Epitopes; Endomysial T Lymphocytes; Myositis; Inclusion Body Myositis; Inflammatory Myopathy