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

M. Salajegheh, G. Rakocevic, Raghavan Pillai Raju, A. Shatunov, L. G. Goldfarb, M. C. Dalakas

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

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 < 0.0001) up to three peaks. Among the amplified subfamilies, Vβ 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 Vβ subfamilies and their change over time suggests recognition of various local antigens and epitope spreading.

Original languageEnglish (US)
Pages (from-to)1672-1679
Number of pages8
JournalNeurology
Volume69
Issue number17
DOIs
StatePublished - Jan 1 2007
Externally publishedYes

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Inclusion Body Myositis
T-Cell Antigen Receptor
Lymphocytes
Muscles
T-Lymphocytes
Epitopes
Immunohistochemistry
Biopsy
Normal Distribution
Clone Cells
Antigens

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Salajegheh, M., Rakocevic, G., Raju, R. P., Shatunov, A., Goldfarb, L. G., & Dalakas, M. C. (2007). T cell receptor profiling in muscle and blood lymphocytes in sporadic inclusion body myositis. Neurology, 69(17), 1672-1679. https://doi.org/10.1212/01.wnl.0000265398.77681.09

T cell receptor profiling in muscle and blood lymphocytes in sporadic inclusion body myositis. / Salajegheh, M.; Rakocevic, G.; Raju, Raghavan Pillai; Shatunov, A.; Goldfarb, L. G.; Dalakas, M. C.

In: Neurology, Vol. 69, No. 17, 01.01.2007, p. 1672-1679.

Research output: Contribution to journalArticle

Salajegheh, M, Rakocevic, G, Raju, RP, Shatunov, A, Goldfarb, LG & Dalakas, MC 2007, 'T cell receptor profiling in muscle and blood lymphocytes in sporadic inclusion body myositis', Neurology, vol. 69, no. 17, pp. 1672-1679. https://doi.org/10.1212/01.wnl.0000265398.77681.09
Salajegheh, M. ; Rakocevic, G. ; Raju, Raghavan Pillai ; Shatunov, A. ; Goldfarb, L. G. ; Dalakas, M. C. / T cell receptor profiling in muscle and blood lymphocytes in sporadic inclusion body myositis. In: Neurology. 2007 ; Vol. 69, No. 17. pp. 1672-1679.
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AU - Goldfarb, L. G.

AU - Dalakas, M. C.

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N2 - 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 < 0.0001) up to three peaks. Among the amplified subfamilies, Vβ 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 Vβ subfamilies and their change over time suggests recognition of various local antigens and epitope spreading.

AB - 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 < 0.0001) up to three peaks. Among the amplified subfamilies, Vβ 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 Vβ subfamilies and their change over time suggests recognition of various local antigens and epitope spreading.

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