Human leukocyte antigen class I in polymyositis: leukocyte infiltrates, regeneration, and impulse block.
In polymyositis (PM), T-cell mediated myocytotoxicity is directed against strongly human leukocyte antigen class I positive (HLA-I+) muscle fibers. Fiber regeneration probably is partly responsible for this HLA-I up-regulation. We have evaluated regeneration, denervation/impulse blockade, and focal leukocyte infiltrates as possible HLA-I inducing factors in PM. Distinctive patterns of HLA-I, nerve cell adhesion molecule (NCAM), and vimentin expression accompany denervation and regeneration. Regenerating fibers also have centralized nuclei. Using semiquantitative methods, we examined strongly HLA-I+ fibers in PM muscle biopsies for these markers. Sarcoplasmic HLA-I levels were related to the presence of leukocyte infiltrates and invasion of fibers. Strongly HLA-I+ fibers were frequently invaded, and regeneration-associated changes were usually observed at sites of fiber damage. Sarcoplasmic HLA-I levels were stable along intact fibers, also adjacent to leukocyte infiltrates. A majority of the strongly HLA-I+ fibers were nonregenerating (NCAM+ only). Though other mechanisms cannot be excluded, this suggests that impulse blockade or denervation may contribute to extra HLA-I up-regulation in these fibers.
Fladby
T
T
Department of Neurology, University Hospital of Tromsø, Norway.
Kampman
M T
MT
Løseth
S
S
Lindal
S
S
Mellgren
S I
SI
D000368:Aged; D015395:Histocompatibility Antigens Class I / Q000032:analysis*; D006801:Humans; D007158:Immunologic Techniques; D007962:Leukocytes / Q000276:immunology*; D008875:Middle Aged; D009121:Muscle Denervation; D018485:Muscle Fibers, Skeletal / Q000145:classification / Q000502:physiology; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism; D017285:Polymyositis / Q000276:immunology*; D012038:Regeneration / Q000502:physiology; D012508:Sarcolemma / Q000276:immunology; D012519:Sarcoplasmic Reticulum / Q000276:immunology; D013194:Staining and Labeling
D015395:Histocompatibility Antigens Class I; D019006:Neural Cell Adhesion Molecules