Elevated plasma complement components in facioscapulohumeral dystrophy

Human Molecular Genetics, vol. 31, pp. 1821–1829

Abstract

Advances in understanding the pathophysiology of facioscapulohumeral dystrophy (FSHD) have led to several therapeutic approaches entering clinical trials and an increased need to develop biomarkers of disease activity and progression. Multiple prior studies have shown early elevation of RNAs encoding components of the complement pathways and relatively widespread activated complement complexes by immunodetection in FSHD muscle. The current study tested plasma from two independent cohorts of FSHD and control subjects and found elevated complement components in both FSHD cohorts. Combining subjects from both cohorts identified complement factors that best distinguished FSHD and controls. Within the FSHD group, a subset of subjects showed elevation in multiple complement components. Together these findings suggest the need for future studies to determine whether measurements of complement activation can be used as a non-invasive measurement of FSHD disease activity, progression and/or response to therapies. In addition, with the ongoing expansion of complement therapeutic approaches, consideration for precision-based targeting of this pathway is appropriate.

Authors 8

1. Chao-Jen Wong

   Fred Hutch Cancer Center

   Affiliation as printed

   Division of Human Biology, Fred Hutchinson Cancer Research Center , Seattle, WA 98109 , USA

2. Leo L. Wang

   University of Washington

   Affiliation as printed

   Department of Neurology , , Seattle, WA 98105 , USA

   University of Washington , , Seattle, WA 98105 , USA

   Department of Neurology, University of Washington, Seattle, WA 98105, USA

3. V. Michael Holers

   University of Colorado Anschutz · University of Colorado Denver

   Affiliation as printed

   Division of Rheumatology , , Aurora, CO 80045 , USA

   University of Colorado School of Medicine , , Aurora, CO 80045 , USA

   Division of Rheumatology, University of Colorado School of Medicine, Aurora, CO 80045, USA

4. Ashley A. Frazer‐Abel

   University of Colorado Anschutz · University of Colorado Denver

   Affiliation as printed

   Exsera BioLabs , Division of Rheumatalogy, , Aurora, CO 80045 , USA

   University of Colorado School of Medicine , Division of Rheumatalogy, , Aurora, CO 80045 , USA

   Exsera BioLabs, Division of Rheumatalogy, University of Colorado School of Medicine, Aurora, CO 80045, USA

5. Silvère M. van der Maarel Aachen Department of Human Genetics Department of Human Genetics

   Leiden University · Leiden University Medical Center

   Affiliation as printed

   Department of Human Genetics , , Leiden 2333 , The Netherlands

   Leiden University Medical Center , , Leiden 2333 , The Netherlands

   Department of Human Genetics, Leiden University Medical Center, Leiden 2333, The Netherlands

6. Rabi Tawil corresponding

   University of Rochester Medicine

   Affiliation as printed

   Department of Neurology , , Rochester, NY 14642 , USA

   University of Rochester Medical Center , , Rochester, NY 14642 , USA

   Department of Neurology, University of Rochester Medical Center, Rochester, NY 14642, USA

7. Jeffrey M. Statland corresponding

   University of Kansas Medical Center

   Affiliation as printed

   Department of Neurology , , Kansas City, KA 66160 , USA

   University of Kansas Medical Center , , Kansas City, KA 66160 , USA

   Department of Neurology, University of Kansas Medical Center, Kansas City, KA 66160, USA

8. Stephen J. Tapscott corresponding

   University of Washington · Fred Hutch Cancer Center

   Affiliation as printed

   Department of Neurology , , Seattle, WA 98105 , USA

   Division of Human Biology, Fred Hutchinson Cancer Research Center , Seattle, WA 98109 , USA

   University of Washington , , Seattle, WA 98105 , USA

   Department of Neurology, University of Washington, Seattle, WA 98105, USA