Affinity proteomics within rare diseases: a <scp>BIO</scp>‐<scp>NMD</scp> study for blood biomarkers of muscular dystrophies

Ayoglu, Burcu; Chaouch, Amina; Lochmüller, Hanns; Politano, Luisa; Bertini, Enrico; Spitali, Pietro; Hiller, Monika; Niks, Erik H.; Gualandi, Francesca; Pontén, Fredrik; Bushby, Kate; Aartsma‐Rus, Annemieke; Schwartz, Elena; Priol, Yannick Le; Straub, Volker; Uhlén, Mathias; Çırak, Sebahattin; Hoen, Peter A.C. ‘t; Muntoni, F.; Ferlini, Alessandra; Schwenk, Jochen M.; Nilsson, Peter; Szigyarto, Cristina Al‐Khalili

doi:10.15252/emmm.201303724

Cited by 101 publications

(145 citation statements)

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“…Decreased levels of AMFR found in plasma from osteoporosis patients may reflect a lower level of physical activity in osteoporotic patients, when considering that transcripts were abundant in skeletal muscle and mirroring a reduced turnaround in muscle proteins. In other recent studies on neuromuscular dystrophy 31 and childhood malaria 32, other muscle proteins have been detected in plasma as indicators of disease.…”

Section: Discussionmentioning

confidence: 99%

Affinity proteomics discovers decreased levels of AMFR in plasma from Osteoporosis patients

Qundos

Drobin

Mattsson

et al. 2015

Proteomics Clinical Apps

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PurposeAffinity proteomic approaches by antibody bead arrays enable multiplexed analysis of proteins in body fluids. In the presented study, we investigated blood plasma within osteoporosis to discovery differential protein profiles and to propose novel biomarkers candidates for subsequent studies.Experimental designStarting with 4608 antibodies and plasma samples from 22 women for an untargeted screening, a set of 72 proteins were suggested for further analysis. Complementing these with targets from literature and other studies, a targeted bead array of 180 antibodies was built to profile for 92 proteins in plasma samples of 180 women from two independent population‐based studies.ResultsDifferential profiles between osteoporosis patients and matched controls were discovered for 12 proteins in at least one of the two study sets. Among these targets, the levels of autocrine motility factor receptor (AMFR) were concordantly lower in plasma of female osteoporosis patients. Subsequently, verification of anti‐AMFR antibody selectivity was conducted using high‐density peptide and protein arrays, and Western blotting.Conclusions and clinical relevanceFurther validation in additional study sets will be needed to determine the clinical value of the observed decrease in AMFR plasma levels in osteoporosis patients, but AMFR may aid our understanding of disease mechanisms and could support existing tools for diagnosis and monitoring of patient mobility within osteoporosis.

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Section: Discussionmentioning

confidence: 99%

Affinity proteomics discovers decreased levels of AMFR in plasma from Osteoporosis patients

Qundos

Drobin

Mattsson

et al. 2015

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“…CK leak from muscle into serum is a general phenomenon; recent studies suggest that a number of muscle proteins leak into serum, including titin, malate dehydrogenase 2, carbonic anhydrase III, and myosin heavy chain 1. 47,48 The absence of dystrophin renders the sarcolemma fragile and susceptible to injury, whereas the loss of dysferlin impairs membrane trafficking, including that associated with resealing of sarcolemmal disruptions. The observation of increased FM dye leak in Dysf B6 compared to Dysf 129 fibers is consistent with the elevated serum CK and also is consistent with the molecular signature of delayed resealing observed in the wounding assay.…”

Section: Annexin A6 Translocation To Sites Of Sarcolemmal Disruption mentioning

confidence: 99%

Enhanced Muscular Dystrophy from Loss of Dysferlin Is Accompanied by Impaired Annexin A6 Translocation after Sarcolemmal Disruption

Demonbreun

Allen

Warner

et al. 2016

The American Journal of Pathology

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Dysferlin is a membrane-associated protein implicated in membrane resealing; loss of dysferlin leads to muscular dystrophy. We examined the same loss-of-function Dysf mutation in two different mouse strains, 129T2/SvEmsJ (Dysf 129 ) and C57BL/6J (Dysf B6 ). Although there are many genetic differences between these two strains, we focused on polymorphisms in Anxa6 because these variants were previously associated with modifying a pathologically distinct form of muscular dystrophy and increased the production of a truncated annexin A6 protein. Dysferlin deficiency in the C57BL/6J background was associated with increased Evan's Blue dye uptake into muscle and increased serum creatine kinase compared to the 129T2/SvEmsJ background. In the C57BL/6J background, dysferlin loss was associated with enhanced pathologic severity, characterized by decreased mean fiber cross-sectional area, increased internalized nuclei, and increased fibrosis, compared to that in Dysf 129 mice. Macrophage infiltrate was also increased in Dysf B6 muscle. High-resolution imaging of live myofibers demonstrated that fibers from Dysf B6 mice displayed reduced translocation of full-length annexin A6 to the site of laser-induced sarcolemmal disruption compared to Dysf 129 myofibers, and impaired translocation of annexin A6 associated with impaired resealing of the sarcolemma. These results provide one mechanism by which the C57BL/6J background intensifies dysferlinopathy, giving rise to a more severe form of muscular dystrophy in the Dysf B6 mouse model through increased membrane leak and inflammation. (Am J Pathol 2016 http://dx

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“…35, 36, 37, 38, 39, 40, 41, 42 Serum and plasma samples were used in biomarker discovery and validation, in particular by the EC-funded BIO-NMD project. 43 …”

Section: Achievements and Recognitionmentioning

confidence: 99%

The EuroBioBank Network: 10 years of hands-on experience of collaborative, transnational biobanking for rare diseases

et al. 2014

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The EuroBioBank (EBB) network (www.eurobiobank.org) is the first operating network of biobanks in Europe to provide human DNA, cell and tissue samples as a service to the scientific community conducting research on rare diseases (RDs). The EBB was established in 2001 to facilitate access to RD biospecimens and associated data; it obtained funding from the European Commission in 2002 (5th framework programme) and started operation in 2003. The set-up phase, during the EC funding period 2003–2006, established the basis for running the network; the following consolidation phase has seen the growth of the network through the joining of new partners, better network cohesion, improved coordination of activities, and the development of a quality-control system. During this phase the network participated in the EC-funded TREAT-NMD programme and was involved in planning of the European Biobanking and Biomolecular Resources Research Infrastructure. Recently, EBB became a partner of RD-Connect, an FP7 EU programme aimed at linking RD biobanks, registries, and bioinformatics data. Within RD-Connect, EBB contributes expertise, promotes high professional standards, and best practices in RD biobanking, is implementing integration with RD patient registries and ‘omics' data, thus challenging the fragmentation of international cooperation on the field.

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Affinity proteomics within rare diseases: a BIO‐NMD study for blood biomarkers of muscular dystrophies

Cited by 101 publications

References 74 publications

Affinity proteomics discovers decreased levels of AMFR in plasma from Osteoporosis patients

Affinity proteomics discovers decreased levels of AMFR in plasma from Osteoporosis patients

Enhanced Muscular Dystrophy from Loss of Dysferlin Is Accompanied by Impaired Annexin A6 Translocation after Sarcolemmal Disruption

The EuroBioBank Network: 10 years of hands-on experience of collaborative, transnational biobanking for rare diseases

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