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Plasma cells in muscle in inclusion body myositis and polymyositis

From the Department of Neurology, Division of Neuromuscular Disease (Drs. Greenberg, Bradshaw, and Amato), Center for Neurologic Disease (Drs. Bradshaw, Bregoli, and O’Connor) and Department of Pathology (Drs. J.L. Pinkus and G.S. Pinkus, B. Due), Brigham and Women’s Hospital and Harvard Medical School, Children’s Hospital Informatics Program (Drs. Greenberg and Bradshaw) and Program in Genomics (T. Burleson), Children’s Hospital, and Affiliated Faculty of the Harvard–MIT Division of Health Sciences and Technology (Dr. Greenberg), Boston, MA.

Address correspondence and reprint requests to Dr Greenberg, Department of Neurology, Brigham and Women’s Hospital, 75 Francis St., Boston, MA 02115; e-mail: sagreenberg{at}partners.org

Background: Previous immunohistochemical studies of muscle from patients with inclusion body myositis and polymyositis found many more T cells than B cells, suggesting a role for intramuscular cell-mediated immune mechanisms rather than humoral mechanisms.

Methods: Microarray studies were performed on muscle biopsy specimens from 40 patients with inclusion body myositis (IBM; n = 23), polymyositis (PM; n = 6), and without neuromuscular disease (n = 11). Reverse transcription PCR of selected immunoglobulin gene transcripts was performed on two patient samples. Qualitative immunohistochemical studies for B-cell lineage cell surface markers were performed on 28 muscle specimens and quantitative studies performed on a subset of 19 untreated patients with IBM or PM. CD138⁺ cells were isolated from muscle using laser capture microdissection, and immunoglobulin transcripts were PCR amplified to determine the presence or absence of immunoglobulin gene rearrangements unique to the B-cell lineage.

Results: Immunoglobulin gene transcripts accounted for 59% in IBM and 33% in PM of the most stringently defined highest differentially expressed muscle transcripts compared with normal. Plasma cells, terminally differentiated B cells expressing CD138 but not CD19 or CD20, are present in IBM and PM muscle in numbers several times higher than B cells.

Conclusions: There are differentiated B cells in the form of CD138⁺ plasma cells within the muscle of patients with inclusion body myositis and polymyositis. The principle of linked recognition of B-cell activation predicts several strategies for autoantigen discovery that could not otherwise be pursued through the study of the infiltrating T-cell population alone.

Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of Contents for the December 13 issue to find the title link for this article.

Supported by grants to S.A.G. from the Muscular Dystrophy Association and the National Institute of Neurological Disorders and Stroke of the NIH. Microarray data were generated by the Children’s Hospital Gene Expression Core (NS40828). K.C.O. is a Career Transition Fellow of the National Multiple Sclerosis Society. L.B is an advanced postdoctoral fellow of the National Multiple Sclerosis Society.

Disclosure: The authors report no conflicts of interest.

Received April 13, 2005. Accepted in final form August 18, 2005.

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