Abstract #8

Presenter

I earned my undergraduate degree from the University of Cambridge, my medical degree from the University of Vienna and a
PhD in Pathology and Laboratory Medicine from the University of British Columbia. After two years in medical genetics at the
University of Innsbruck, Austria, I returned to UBC and completed specialist training in Neuropathology, followed by a fellowship
in Neuromuscular Pathology at the UCL Institute of Neurology, Queen Square, London UK. I am a staff neuropathologist at VGH
with special interest in myopathology and a lead role for the VGH Muscle Lab. My research has focussed on inflammatory
myopathies and I see considerable potential to pursue this further at UBC. Outside work I spend most of my time with my family
of four. I enjoy skiing, good music, and a good book.

Authors

Peter W. Schutz¹, Simon Cheung¹, Lin Yi², Fabio M.V. Rossi²

¹Department of Pathology, University of British Columbia and Vancouver General Hospital, Vancouver, BC, V6T 2B5, Canada.

²Biomedical Research Centre, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada.

CanMEDS:
Medical Expert (the integrating role),  Scholar

Cellular activation patterns of CD10+ fibro-adipogenic progenitors across acquired disease states in human skeletal muscle biopsies. 

Background 

Fibro-adipogenic progenitors (FAP) are resident mesenchymal stem cells of skeletal muscle with defined roles in muscle fiber repair and fibrosis. Experimental studies have shown their involvement in fibrofatty degeneration, denervation atrophy, and their susceptibility for pharmacological intervention. FAP reaction patterns in human muscle biopsies are largely unknown, but have potential to inform translational approaches. 

Method

32 muscle biopsies from the archives of Vancouver General Hospital were selected from 8 groups (normal, dermatomyositis, IBM, anti-synthetase syndrome, IMNM, denervation, type 2 atrophy, rhabdomyolysis). FAP reaction patterns were analysed on routine CD10 immunohistochemical staining and compared between groups. Double staining with MxA was performed on a subset. Groups were compared histologically and by semi-quantitative scoring. 

Results 

Activated endomysial CD10+ FAPs showed thickening and expansion of their normally delicate cell processes surrounding muscle fibers, and endomysial cell clusters evidencing proliferation. Comparison across groups confirms FAP activation in association with fiber degeneration/regeneration, foci of inflammation, and denervation, in keeping with experimental results. Unexpectedly, dermatomyositis and anti-synthetase biopsies show diffuse activation. FAP activation in dermatomyositis coincided with sarcoplasmic MxA expression.   

Conclusion 

Assessment of CD10+ FAP activation is routinely possible using CD10 immunohistochemistry and demonstrates cellular FAP reaction patterns often in keeping with preclinical results. Prominent expansion of FAP processes surrounding myofibers suggests enhanced interaction between myofiber/basement membranes and FAPs during activation. The presence of diffuse FAP activation in dermatomyositis and anti-synthetase biopsies raises the possibility of FAP activation as part of the autoimmune process. Future diagnostic applications, clinical significance and therapeutic potential remain open questions.