Integration of known DNA, RNA and protein biomarkers provides prediction of anti-TNF response in rheumatoid arthritis: results from the COMBINE study
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Integration of known DNA, RNA and protein biomarkers provides prediction of anti-TNF response in rheumatoid arthritis : results from the COMBINE study. / Folkersen, Lasse; Brynedal, Boel; Diaz-Gallo, Lina Marcela; Ramsköld, Daniel; Shchetynsky, Klementy; Westerlind, Helga; Sundström, Yvonne; Schepis, Danika; Hensvold, Aase; Vivar, Nancy; Eloranta, Maija-Leena; Rönnblom, Lars; Brunak, Søren; Malmström, Vivianne; Catrina, Anca I; Mørch, Ulrik Gw; Klareskog, Lars; Padyukov, Leonid; Berg, Louise.
In: Molecular medicine (Cambridge, Mass.), Vol. 22, 2016, p. 3223328.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Integration of known DNA, RNA and protein biomarkers provides prediction of anti-TNF response in rheumatoid arthritis
T2 - results from the COMBINE study
AU - Folkersen, Lasse
AU - Brynedal, Boel
AU - Diaz-Gallo, Lina Marcela
AU - Ramsköld, Daniel
AU - Shchetynsky, Klementy
AU - Westerlind, Helga
AU - Sundström, Yvonne
AU - Schepis, Danika
AU - Hensvold, Aase
AU - Vivar, Nancy
AU - Eloranta, Maija-Leena
AU - Rönnblom, Lars
AU - Brunak, Søren
AU - Malmström, Vivianne
AU - Catrina, Anca I
AU - Mørch, Ulrik Gw
AU - Klareskog, Lars
AU - Padyukov, Leonid
AU - Berg, Louise
PY - 2016
Y1 - 2016
N2 - OBJECTIVE: In rheumatoid arthritis (RA) several recent efforts have sought to discover means of predicting which patients would benefit from treatment. However, results have been discrepant with few successful replications. Our objective was to build a biobank with DNA, RNA and protein measurements to test the claim that the current state-of-the-art precision medicine will benefit RA patients.METHODS: We collected 451 blood samples from 61 healthy individuals and 185 RA patients initiating treatment, before treatment initiation and at a 3 month follow-up time. All samples were subjected to high-throughput RNA sequencing, DNA genotyping, extensive proteomics and flow cytometry measurements, as well as comprehensive clinical phenotyping. Literature review identified 2 proteins, 52 single-nucleotide polymorphisms (SNPs) and 72 gene-expression biomarkers that had previously been proposed as predictors of TNF inhibitor response (∆DAS28-CRP).RESULTS: From these published TNFi biomarkers we found that 2 protein, 2 SNP and 8 mRNA biomarkers could be replicated in the 59 TNF initiating patients. Combining these replicated biomarkers into a single signature we found that we could explain 51% of the variation in ∆DAS28-CRP. This corresponds to a sensitivity of 0.73 and specificity of 0.78 for the prediction of three month ∆DAS28-CRP better than -1.2.CONCLUSIONS: The COMBINE biobank is currently the largest collection of multi-omics data from RA patients with high potential for discovery and replication. Taking advantage of this we surveyed the current state-of-the-art of drug-response stratification in RA, and identified a small set of previously published biomarkers available in peripheral blood which predicts clinical response to TNF blockade in this independent cohort.
AB - OBJECTIVE: In rheumatoid arthritis (RA) several recent efforts have sought to discover means of predicting which patients would benefit from treatment. However, results have been discrepant with few successful replications. Our objective was to build a biobank with DNA, RNA and protein measurements to test the claim that the current state-of-the-art precision medicine will benefit RA patients.METHODS: We collected 451 blood samples from 61 healthy individuals and 185 RA patients initiating treatment, before treatment initiation and at a 3 month follow-up time. All samples were subjected to high-throughput RNA sequencing, DNA genotyping, extensive proteomics and flow cytometry measurements, as well as comprehensive clinical phenotyping. Literature review identified 2 proteins, 52 single-nucleotide polymorphisms (SNPs) and 72 gene-expression biomarkers that had previously been proposed as predictors of TNF inhibitor response (∆DAS28-CRP).RESULTS: From these published TNFi biomarkers we found that 2 protein, 2 SNP and 8 mRNA biomarkers could be replicated in the 59 TNF initiating patients. Combining these replicated biomarkers into a single signature we found that we could explain 51% of the variation in ∆DAS28-CRP. This corresponds to a sensitivity of 0.73 and specificity of 0.78 for the prediction of three month ∆DAS28-CRP better than -1.2.CONCLUSIONS: The COMBINE biobank is currently the largest collection of multi-omics data from RA patients with high potential for discovery and replication. Taking advantage of this we surveyed the current state-of-the-art of drug-response stratification in RA, and identified a small set of previously published biomarkers available in peripheral blood which predicts clinical response to TNF blockade in this independent cohort.
KW - Journal Article
U2 - 10.2119/molmed.2016.00078
DO - 10.2119/molmed.2016.00078
M3 - Journal article
C2 - 27532898
VL - 22
SP - 3223328
JO - Molecular Medicine
JF - Molecular Medicine
SN - 1076-1551
ER -
ID: 177048389