Elevated Plasma Complement Components in Facioscapulohumeral Dystrophy

Overview

Journal Hum Mol Genet

Specialties Genetics
Molecular Biology

Date 2021 Dec 17

PMID 34919696

Citations 5

Authors

Chao-Jen Wong

Leo Wang

V Michael Holers

Ashley Frazer-Abel

Silvere M van der Maarel

Rabi Tawil

Jeffrey M Statland

Stephen J Tapscott

Affiliations

Soon will be listed here.

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.

Citing Articles

Facioscapulohumeral Dystrophy: Molecular Basis and Therapeutic Opportunities.

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Campbell A, Arjomand J, King O, Tawil R, Jagannathan S J Neuromuscul Dis. 2023; 10(6):1031-1040.

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The FSHD muscle-blood biomarker: a circulating transcriptomic biomarker for clinical severity in facioscapulohumeral muscular dystrophy.

Banerji C, Greco A, Joosten L, van Engelen B, Zammit P Brain Commun. 2023; 5(5):fcad221.

PMID: 37731904 PMC: 10507741. DOI: 10.1093/braincomms/fcad221.

References

Statland J, Shah B, Henderson D, van der Maarel S, Tapscott S, Tawil R . Muscle pathology grade for facioscapulohumeral muscular dystrophy biopsies. Muscle Nerve. 2015; 52(4):521-6. PMC: 4546927. DOI: 10.1002/mus.24621. View

Frisullo G, Frusciante R, Nociti V, Tasca G, Renna R, Iorio R . CD8(+) T cells in facioscapulohumeral muscular dystrophy patients with inflammatory features at muscle MRI. J Clin Immunol. 2010; 31(2):155-66. DOI: 10.1007/s10875-010-9474-6. View

Tortajada A, Yebenes H, Abarrategui-Garrido C, Anter J, Garcia-Fernandez J, Martinez-Barricarte R . C3 glomerulopathy-associated CFHR1 mutation alters FHR oligomerization and complement regulation. J Clin Invest. 2013; 123(6):2434-46. PMC: 3668852. DOI: 10.1172/JCI68280. View

Liszewski M, Farries T, Lublin D, Rooney I, Atkinson J . Control of the complement system. Adv Immunol. 1996; 61:201-83. DOI: 10.1016/s0065-2776(08)60868-8. View

Statland J, Donlin-Smith C, Tapscott S, van der Maarel S, Tawil R . Multiplex Screen of Serum Biomarkers in Facioscapulohumeral Muscular Dystrophy. J Neuromuscul Dis. 2015; 1(2):181-190. PMC: 4332410. DOI: 10.3233/JND-140034. View

Greco A, Straasheijm K, Mul K, van den Heuvel A, van der Maarel S, Joosten L . Profiling Serum Antibodies Against Muscle Antigens in Facioscapulohumeral Muscular Dystrophy Finds No Disease-Specific Autoantibodies. J Neuromuscul Dis. 2021; 8(5):801-814. PMC: 9789485. DOI: 10.3233/JND-210653. View

Rahimov F, King O, Leung D, Bibat G, Emerson Jr C, Kunkel L . Transcriptional profiling in facioscapulohumeral muscular dystrophy to identify candidate biomarkers. Proc Natl Acad Sci U S A. 2012; 109(40):16234-9. PMC: 3479603. DOI: 10.1073/pnas.1209508109. View

Halkjaer L, Troldborg A, Pedersen H, Jensen L, Hansen A, Hansen T . Complement Receptor 2 Based Immunoassay Measuring Activation of the Complement System at C3-Level in Plasma Samples From Mice and Humans. Front Immunol. 2020; 11:774. PMC: 7214740. DOI: 10.3389/fimmu.2020.00774. View

Wang L, Tawil R . Current Therapeutic Approaches in FSHD. J Neuromuscul Dis. 2021; 8(3):441-451. PMC: 8203219. DOI: 10.3233/JND-200554. View

10.

Tawil R, van der Maarel S, Tapscott S . Facioscapulohumeral dystrophy: the path to consensus on pathophysiology. Skelet Muscle. 2014; 4:12. PMC: 4060068. DOI: 10.1186/2044-5040-4-12. View

11.

Foss C, Kulik L, Ordonez A, Jain S, Holers V, Thurman J . SPECT/CT Imaging of Mycobacterium tuberculosis Infection with [I]anti-C3d mAb. Mol Imaging Biol. 2018; 21(3):473-481. PMC: 6329677. DOI: 10.1007/s11307-018-1228-5. View

12.

Schatzl T, Kaiser L, Deigner H . Facioscapulohumeral muscular dystrophy: genetics, gene activation and downstream signalling with regard to recent therapeutic approaches: an update. Orphanet J Rare Dis. 2021; 16(1):129. PMC: 7953708. DOI: 10.1186/s13023-021-01760-1. View

13.

Lassche S, Kusters B, Heerschap A, Schyns M, Ottenheijm C, Voermans N . Correlation Between Quantitative MRI and Muscle Histopathology in Muscle Biopsies from Healthy Controls and Patients with IBM, FSHD and OPMD. J Neuromuscul Dis. 2020; 7(4):495-504. PMC: 7739972. DOI: 10.3233/JND-200543. View

14.

Dahlqvist J, Andersen G, Khawajazada T, Vissing C, Thomsen C, Vissing J . Relationship between muscle inflammation and fat replacement assessed by MRI in facioscapulohumeral muscular dystrophy. J Neurol. 2019; 266(5):1127-1135. DOI: 10.1007/s00415-019-09242-y. View

15.

Dahlqvist J, Poulsen N, Ostergaard S, Fornander F, Borch J, Danielsen E . Evaluation of inflammatory lesions over 2 years in facioscapulohumeral muscular dystrophy. Neurology. 2020; 95(9):e1211-e1221. DOI: 10.1212/WNL.0000000000010155. View

16.

Carregari V, Monforte M, di Maio G, Pieroni L, Urbani A, Ricci E . Proteomics of Muscle Microdialysates Identifies Potential Circulating Biomarkers in Facioscapulohumeral Muscular Dystrophy. Int J Mol Sci. 2021; 22(1). PMC: 7795508. DOI: 10.3390/ijms22010290. View

17.

Skattum L . Clinical Complement Analysis-An Overview. Transfus Med Rev. 2019; 33(4):207-216. DOI: 10.1016/j.tmrv.2019.09.001. View

18.

Ferguson M, Poliachik S, Budech C, Gove N, Carter G, Wang L . MRI change metrics of facioscapulohumeral muscular dystrophy: Stir and T1. Muscle Nerve. 2017; 57(6):905-912. DOI: 10.1002/mus.26038. View

19.

Mastellos D, Ricklin D, Sfyroera G, Sahu A . From discovery to approval: A brief history of the compstatin family of complement C3 inhibitors. Clin Immunol. 2021; 235:108785. DOI: 10.1016/j.clim.2021.108785. View

20.

Fujita T, Matsushita M, Endo Y . The lectin-complement pathway--its role in innate immunity and evolution. Immunol Rev. 2004; 198:185-202. DOI: 10.1111/j.0105-2896.2004.0123.x. View