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Proteomic technologies have ushered in a new era in biomarker discovery that may revolutionize the diagnosis and treatment of rheumatic diseases.
Technological innovations in the past decade have transformed the understanding and treatment of rheumatic diseases, according to a review published in the new issue of Nature Reviews Rheumatology. The authors, led by William H. Robinson of Stanford University, anticipate that “high-throughput approaches, especially those allowing for single-cell resolution, will move to the mainstream of rheumatology research and form the basis for next-generation diag¬nostics.” Innovations in proteomics, which include advances in mass spectrometry and the emergence of protein-array technologies, have revolu¬tionized the identification of proteins and post-translational modifications associated with rheumatic diseases. “Several of the proteomic profiles gleaned with these technologies have potential for use as actionable biomarkers in predictive medicine,” they stated.
They believe that proteomic technologies have ushered in a new era in biomarker discovery that may revolutionize the diagnosis and treatment of rheumatic diseases.
Another “technological tour de force” that has trans¬formed rheumatology is large-scale sequencing. “The advent of high-throughput DNA sequencing has made possible sequencing of the genome to iden¬tify both common and rare genetic variants associated with rheumatic diseases. This method can also be applied to sequenc¬ing the expressed genome, which includes thousands of gene transcripts that reflect activation and repression of pathways involved in rheumatic diseases,” they stated. Large-scale DNA sequencing can now digitally define the functional antibodies and T cell receptors in autoimmune rheumatic diseases, and epigenetic technologies can probe disease-associated changes in DNA methylation and histone modification. In addition, the development of mass cytometry and considerable advances in flow cytom¬etry have enhanced the ability to analyze cellular markers and signaling pathways in rheumatic diseases. Recently, magnetic resonance imagining (MRI) and ultrasonography have been incorporated into routine practice in rheumatology. They allow for better assessment of soft-tissue abnormali¬ties and detecting bone erosions than conventional radiology. Clinicians have also begun to use them as noninvasive tools to detect subclinical inflammation and progression of joint damage. “By enabling serial assessment of synovitis, interval imaging via MRI or ultrasonography yields dynamic biomarkers that are useful for monitoring the progression of disease or its response to therapy,” they stated. Also, advances in stem-cell technologies now offer new opportuni¬ties in tissue engineering and regenerative rheumatology. They cited recent work on the small molecule kartogenin, which has been shown to direct differentiation of mesenchymal stem cells into chondrocytes and repair damaged carti¬lage. “Given the heterogeneity of most rheumatic diseases, the diverse molecular pathways mediating their pathogenesis and the multifaceted roles that these pathways have in normal and pathological states, advances in treatment are likely to require approaches that inte¬grate genomic, transcriptomic, proteomic, metabolomic and autoantibody profiles, such as the recently described integrative personal omics profile,” they concluded.
Robinson WH et al. “Decade in review-technology: Technological advances transforming rheumatology.” Nature Reviews Rheumatology 2015 Nov;11(11):626-8. doi: 10.1038/nrrheum.2015.137. Epub 2015 Oct 6.