Plasma cells in muscle in inclusion body myositis and polymyositis.
BACKGROUND
Previous immunohistochemical studies of muscle from patients with inclusion body myositis and polymyositis found many more T cells than B cells, suggesting a role for intramuscular cell-mediated immune mechanisms rather than humoral mechanisms.


METHODS
Microarray studies were performed on muscle biopsy specimens from 40 patients with inclusion body myositis (IBM; n = 23), polymyositis (PM; n = 6), and without neuromuscular disease (n = 11). Reverse transcription PCR of selected immunoglobulin gene transcripts was performed on two patient samples. Qualitative immunohistochemical studies for B-cell lineage cell surface markers were performed on 28 muscle specimens and quantitative studies performed on a subset of 19 untreated patients with IBM or PM. CD138+ cells were isolated from muscle using laser capture microdissection, and immunoglobulin transcripts were PCR amplified to determine the presence or absence of immunoglobulin gene rearrangements unique to the B-cell lineage.


RESULTS
Immunoglobulin gene transcripts accounted for 59% in IBM and 33% in PM of the most stringently defined highest differentially expressed muscle transcripts compared with normal. Plasma cells, terminally differentiated B cells expressing CD138 but not CD19 or CD20, are present in IBM and PM muscle in numbers several times higher than B cells.


CONCLUSIONS
There are differentiated B cells in the form of CD138+ plasma cells within the muscle of patients with inclusion body myositis and polymyositis. The principle of linked recognition of B-cell activation predicts several strategies for autoantigen discovery that could not otherwise be pursued through the study of the infiltrating T-cell population alone.
Greenberg
S A
SA
Division of Neuromuscular Disease, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. sagreenberg@partners.org
Bradshaw
E M
EM
Pinkus
J L
JL
Pinkus
G S
GS
Burleson
T
T
Due
B
B
Bregoli
L
L
Bregoli
L S
LS
O'Connor
K C
KC
Amato
A A
AA
D000954:Antigens, Surface / Q000235:genetics / Q000276:immunology; D001324:Autoantigens / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics / Q000276:immunology; D007150:Immunohistochemistry; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology; D018482:Muscle, Skeletal / Q000276:immunology* / Q000473:pathology* / Q000503:physiopathology; D018979:Myositis, Inclusion Body / Q000175:diagnosis* / Q000276:immunology* / Q000503:physiopathology; D010950:Plasma Cells / Q000276:immunology* / Q000473:pathology; D017285:Polymyositis / Q000175:diagnosis* / Q000276:immunology* / Q000503:physiopathology; D011509:Proteoglycans / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D053668:Syndecan-1; D053667:Syndecans; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology
D000954:Antigens, Surface; D001324:Autoantigens; D015415:Biomarkers; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D011509:Proteoglycans; D012333:RNA, Messenger; C508241:SDC1 protein, human; D053668:Syndecan-1; D053667:Syndecans