Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 201, Issue 4, Pages 591-601Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20041367
Keywords
-
Categories
Funding
- NCI NIH HHS [P50CA088843, P50CA058184, P50 CA058184, P50 CA088843] Funding Source: Medline
- NIAMS NIH HHS [R01 AR044684, AR-44684] Funding Source: Medline
- NIDCR NIH HHS [R01 DE012354, R37 DE012354, DE-12354] Funding Source: Medline
Ask authors/readers for more resources
Unique autoantibody specificities are strongly associated with distinct clinical phenotypes, making autoantibodies useful for diagnosis and prognosis. To investigate the mechanisms underlying this striking association, we examined autoantigen expression in normal muscle and in muscle from patients with autoimmune myositis. Although myositis autoantigens are expressed at very low levels in control muscle, they are found at high levels in myositis muscle. Furthermore, increased autoantigen expression correlates with differentiation state, such that myositis autoantigen expression is increased in cells that have features of regenerating muscle cells. Consistent with this, we found that cultured myoblasts express high levels of autoantigens, which are strikingly down-regulated as cells differentiate into myotubes in vitro. These data strongly implicate regenerating muscle cells rather than mature myotubes as the source of ongoing antigen supply in autoimmune myositis. Myositis autoantigen expression is also markedly increased in several cancers known to be associated with autoimmune myositis, but not in their related normal tissues, demonstrating that tumor cells and undifferentiated myoblasts are antigenically similar. We propose that in cancer-associated myositis, an autoimmune response directed against cancer cross-reacts with regenerating muscle cells, enabling a feed-forward loop of tissue damage and antigen selection. Regulating pathways of antigen expression may provide unrecognized therapeutic opportunities in autoimmune diseases.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available