Interleukin-1alpha expression in capillaries and major histocompatibility complex class I expression in type II muscle fibers from polymyositis and dermatomyositis patients: important pathogenic features independent of inflammatory cell clusters in muscle tissue.
OBJECTIVE
To address the hypothesis that endothelial cells and/or muscle fibers are primary targets in the disease process by analysis of muscle tissue from patients with polymyositis (PM) and dermatomyositis (DM).


METHODS
We included patients with laboratory signs and clinical symptoms typical of myositis, but without detectable infiltration of clusters of inflammatory cells in their muscle biopsy samples. An immunohistochemical technique was applied to identify CD3, CD68, lymphocyte function-associated antigen 1alpha, CD11b, very late activation antigen 4, endothelium 4, interleukin-1alpha (IL-1alpha), intercellular adhesion molecule 1, vascular cell adhesion molecule 1, IgG, IgM, IgA, and HLA-A/B/C in muscle tissue. Fiber type was defined by ATPase staining.


RESULTS
IL-1alpha expression was detected in endothelial cells of capillaries to a greater extent in patients than in controls, and class I major histocompatibility complex (MHC) expression was significantly increased in muscle fibers. We also observed that class I MHC expression was mainly confined to type II muscle fibers.


CONCLUSIONS
Our findings imply that defined molecular changes of blood vessels and muscle fibers are both independent of adjacent inflammatory infiltrates and could thus be primary events in the development of myositis. Moreover, both IL-1alpha and class I MHC molecules might be important for the development of clinical symptoms in PM and DM patients.
Englund
Pernilla
P
Karolinska Institutet, Stockholm, Sweden. pernilla.englund@cmm.ki.se
Nennesmo
Inger
I
Klareskog
Lars
L
Lundberg
Ingrid E
IE
D000328:Adult; D001706:Biopsy; D002196:Capillaries / Q000737:chemistry / Q000378:metabolism; D003882:Dermatomyositis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000032:analysis* / Q000096:biosynthesis; D006650:Histocompatibility Testing; D006801:Humans; D016130:Immunophenotyping; D007375:Interleukin-1 / Q000032:analysis* / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D018656:Muscle Fibers, Fast-Twitch / Q000737:chemistry* / Q000378:metabolism / Q000473:pathology; D018482:Muscle, Skeletal / Q000098:blood supply / Q000276:immunology / Q000473:pathology
D015395:Histocompatibility Antigens Class I; D007375:Interleukin-1