JOURNAL ARTICLE
RESEARCH SUPPORT, N.I.H., INTRAMURAL
RESEARCH SUPPORT, NON-U.S. GOV'T
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T cell receptor profiling in muscle and blood lymphocytes in sporadic inclusion body myositis.

Neurology 2007 October 24
BACKGROUND: Sporadic IBM (sIBM) is characterized by invasion of non-necrotic MHC-I class-expressing muscle fibers by clonally expanded CD8+ cells. Whether the endomysial cells expand in situ or are recruited from the circulation is unclear.

METHODS: We used CDR3 spectratyping of the T cell receptor (TCR) V beta chains to determine clonal expansion of T cells in simultaneously obtained muscle and peripheral blood lymphocytes (PBL) from 12 patients with sIBM, and compared the difference between the two compartments. To determine whether the identified clones belonged to autoinvasive T cells, we performed immunohistochemistry on the same muscle specimens. Spectratyping was repeated in four muscle biopsies 1 year after the first.

RESULTS: In control PBL, all 24 TCR V beta subfamilies had a polyclonal or Gaussian distribution. In sIBM PBL, 5% of the V beta subfamilies demonstrated a single and 16% up to three peaks. In contrast, in their corresponding muscles, 27% (p = 0.0003) of the V beta subfamilies demonstrated a single and 71% (p < 0.0001) up to three peaks. Among the amplified subfamilies, V beta 9, 10, 11, 16, 18, 23, and 24 showed the highest degree of restriction within muscle. Immunohistochemistry demonstrated that the clonally expanded CD8+ cells were autoinvasive. In follow-up biopsies the clonality persisted with an unchanged degree of restriction, but not always of the same subfamilies, suggesting epitope spreading.

CONCLUSION: In sporadic inclusion body myositis, the endomysial T cells are specifically recruited to the muscle or expand in situ. The restriction of multiple V beta subfamilies and their change over time suggests recognition of various local antigens and epitope spreading.

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