T cell receptor profiling in muscle and blood lymphocytes in sporadic inclusion body myositis.

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) Vβ 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 Vβ subfamilies had a polyclonal or Gaussian distribution. In sIBM PBL, 5% of the Vβ subfamilies demonstrated a single and 16% up to three peaks. In contrast, in their corresponding muscles, 27% ( p = 0.0003) of the Vβ subfamilies demonstrated a single and 71% ( p Conclusion: In sporadic inclusion body myositis, the endomysial T cells are specifically recruited to the muscle or expand in situ. The restriction of multiple Vβ subfamilies and their change over time suggests recognition of various local antigens and epitope spreading. GLOSSARY: CDR3 = complementarity-determining-region 3; CK = creatine kinase (normal range 52 to 386 U/L); DAPI = 6-diamidino-2-phenylindole; MRC = Medical Research Council; PBL = peripheral blood lymphocytes; RT-PCR = reverse transcription PCR; sIBM = sporadic inclusion body myositis; TCR = T cell receptor.