Isolated elevation of aldolase in the serum of myositis patients: a potential biomarker of damaged early regenerating muscle cells.
OBJECTIVE
Elevated serum aldolase A levels occur in the absence of elevated creatine kinase M (CK) levels in a subset of myositis patients. This study was undertaken to investigate the cell biology of this unexplained clinical observation.


METHODS
Cultured human myoblasts were differentiated in vitro. RNA and protein lysates were prepared and used to determine aldolase and CK gene and protein expression by QPCR and immunoblotting. Cardiotoxin was used to induce muscle injury and repair in an experimental mouse model, and aldolase A and CK were immunoblotted in the muscle lysates. Immunohistochemical staining was performed on myositis patient muscle paraffin sections to assess aldolase A and CK staining in vivo.


RESULTS
Aldolase A mRNA and protein expression is highest in differentiating myoblasts, and remains robust throughout differentiation. In contrast, CK mRNA and protein levels are low in undifferentiated myoblasts and become strikingly upregulated as differentiation progresses. Aldolase A protein expression is high in regenerating muscle in the mouse model of injury/repair, while CK expression was low. Immunohistochemical staining of human myositis biopsies showed that muscle cells with the highest levels of aldolase and no CK staining have features of regeneration.


CONCLUSIONS
In undifferentiated muscle cells, and those early in the differentiation process, aldolase A is expressed in the absence of CK. Thereafter, both are expressed. We propose that isolated serum aldolase A elevation in myositis patients (i) reflects preferential immune-mediated damage of early regenerative cells, and (ii) is a biomarker of damaged early regenerating muscle cells.
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. lcr@jhmi.edu
Livia
L
Casciola-Rosen
John C
JC
Hall
Andrew L
AL
Mammen
Lisa
L
Christopher-Stine
Antony
A
Rosen
D000818:Animals; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D003402:Creatine Kinase / Q000097:blood; D004195:Disease Models, Animal; D005634:Fructose-Bisphosphate Aldolase / Q000097:blood*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000201:enzymology*; D018482:Muscle, Skeletal / Q000473:pathology / Q000502:physiology; D009220:Myositis / Q000175:diagnosis* / Q000201:enzymology*; D012038:Regeneration / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology
D015415:Biomarkers; D003402:Creatine Kinase; D005634:Fructose-Bisphosphate Aldolase