Inclusion body myositis with human immunodeficiency virus infection

Four cases with clonal expansion of viral-specific T cells

Marinos C. Dalakas, Goran Rakocevic, Alexey Shatunov, Lev Goldfarb, Raghavan Pillai Raju, Mohammad Salajegheh

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Objective: Sporadic inclusion body myositis (sIBM), a common adult-onset myositis, is characterized by an antigen-driven inflammatory tesponse and vacuolar degeneration. The cause is unknown. We report the association of sIBM with human immunodeficiency virus (HIV) infection and explore the clonality and viral specificity of the autoinvasive T cells. Methods: Clinicopathological studies in four HIV-infected patients with IBM were performed. The clonal restriction of endomysial T cells, compared with peripheral blood, was examined by spectratyping. Immunohistochemical studies using human leukocyte antigen-A* 0201-gag tetramers and the most dominant Vb families were performed in serial muscle biopsy sections to examine whether clonally expanded autoinvasive T cells are viral specific and invade muscle fibers expressing the allele-specific monomorphic major histocompatibility complex class I antigen. Results: Prominent clonal restriction of certain Vb families was noted among the endomysial T cells with evidence of in situ expansion. Approximately 10% of the autoinvasive CD8+ cells were human leukocyte antigen-A* 0201-HIV-gag specific and invaded muscle fibers expressing the specific human leukocyte antigen-A* 0201 allele. These cells belonged to restricted Vb families. The HIV gag antigen was present on several endomysial macrophages but not within the muscle fibers. Interpretation: sIBM develops in patients who harbor HIV. In HIV-IBM, a subset of CD8+ T cells surrounding muscle fibers are viral specific and may play a role in the disease mechanism by cross-reacting with antigens on the surface of muscle fibers. This study provides a paradigm that a chronic viral infection in genetically susceptible individuals can trigger viral specific T cell clones that persist within the muscle and lead to development of sIBM.

Original languageEnglish (US)
Pages (from-to)466-475
Number of pages10
JournalAnnals of Neurology
Volume61
Issue number5
DOIs
StatePublished - May 1 2007
Externally publishedYes

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Inclusion Body Myositis
Virus Diseases
HIV
T-Lymphocytes
Muscles
HLA Antigens
Alleles
T-Cell Antigen Receptor Specificity
gag Gene Products
Histocompatibility Antigens Class I
Myositis
T-Lymphocyte Subsets
Surface Antigens
Major Histocompatibility Complex
Clone Cells
Macrophages
Biopsy
Antigens

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Inclusion body myositis with human immunodeficiency virus infection : Four cases with clonal expansion of viral-specific T cells. / Dalakas, Marinos C.; Rakocevic, Goran; Shatunov, Alexey; Goldfarb, Lev; Raju, Raghavan Pillai; Salajegheh, Mohammad.

In: Annals of Neurology, Vol. 61, No. 5, 01.05.2007, p. 466-475.

Research output: Contribution to journalArticle

Dalakas, Marinos C. ; Rakocevic, Goran ; Shatunov, Alexey ; Goldfarb, Lev ; Raju, Raghavan Pillai ; Salajegheh, Mohammad. / Inclusion body myositis with human immunodeficiency virus infection : Four cases with clonal expansion of viral-specific T cells. In: Annals of Neurology. 2007 ; Vol. 61, No. 5. pp. 466-475.
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