Affinity proteomics within rare diseases: a BIO-NMD study for blood biomarkers of muscular dystrophies.
Bottom Line: We addressed this challenge by combining samples collected within the BIO-NMD consortium from four geographically dispersed clinical sites to identify protein markers associated with muscular dystrophy using an antibody bead array platform with 384 antibodies.Based on concordance in statistical significance and confirmatory results obtained from analysis of both serum and plasma, we identified eleven proteins associated with muscular dystrophy, among which four proteins were elevated in blood from muscular dystrophy patients: carbonic anhydrase III (CA3) and myosin light chain 3 (MYL3), both specifically expressed in slow-twitch muscle fibers and mitochondrial malate dehydrogenase 2 (MDH2) and electron transfer flavoprotein A (ETFA).Using age-matched sub-cohorts, 9 protein profiles correlating with disease progression and severity were identified, which hold promise for the development of new clinical tools for management of dystrophinopathies.
Affiliation: Affinity Proteomics, SciLifeLab, School of Biotechnology KTH-Royal Institute of Technology, Stockholm, Sweden.Show MeSH
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Mentions: The comparison across DMD, BMD, and control groups revealed three more potentially interesting proteins, TNNT3, CK, and ETFB (also summarized in Table 2). Interestingly, the profile for ETFB showed an opposite trend (Fig 4) compared to other proteins including ETFA, which belongs to the same heterodimeric protein complex as ETFB. A negative correlation was revealed between the signal intensities for antibodies targeting these two proteins in DMD and BMD groups as compared to controls (Supplementary Table S2). The relationship between ETFA and ETFB was further analyzed by calculation of the ETFB/ETFA MFI value ratios for all the different sample groups and blood preparation types. Both in serum and in plasma, the ratios were highest in the control groups followed by the BMD patients and even lower in DMD (Supplementary Fig S6). Fitting a linear model revealed a statistically significant association between the change of ETFB/ETFA ratio and severity of the phenotype, in both serum and plasma (Fig 5).
Affiliation: Affinity Proteomics, SciLifeLab, School of Biotechnology KTH-Royal Institute of Technology, Stockholm, Sweden.