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Identifying Reliable Diagnostic/Predictive Biomarkers for Rheumatoid Arthritis

INTRODUCTION AND OBJECTIVE: Elevated C-reactive protein is usually a good indicator of rheumatoid arthritis (RA); however, there are limitations that compromise its specificity and therefore there is an urgent need to identify more reliable diagnostic biomarkers to detect early stages of RA. In addi...

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Autores principales: Shervington, Leroy, Darekar, Ashish, Shaikh, Murassa, Mathews, Roshini, Shervington, Amal
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6153528/
https://www.ncbi.nlm.nih.gov/pubmed/30262983
http://dx.doi.org/10.1177/1177271918801005
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author Shervington, Leroy
Darekar, Ashish
Shaikh, Murassa
Mathews, Roshini
Shervington, Amal
author_facet Shervington, Leroy
Darekar, Ashish
Shaikh, Murassa
Mathews, Roshini
Shervington, Amal
author_sort Shervington, Leroy
collection PubMed
description INTRODUCTION AND OBJECTIVE: Elevated C-reactive protein is usually a good indicator of rheumatoid arthritis (RA); however, there are limitations that compromise its specificity and therefore there is an urgent need to identify more reliable diagnostic biomarkers to detect early stages of RA. In addition, identifying the correct therapeutic biomarker for the treatment of RA using methotrexate (MTX) would greatly increase the benefits experienced by the patients. MATERIALS AND METHODS: Primary normal synoviocytes human fibroblast-like synoviocytes (HFLS) and its phenotype rheumatic HFLS-RA cells were chosen for this study. The HFLS-RA–untreated and MTX-treated cells were subjected to microarray analysis. RESULTS: Microarray data identified 74 differentially expressed genes. These genes were mapped against an RA inflammatory pathway, shortlisting 10 candidate genes. Gene expression profiling of the 10 genes were studied. Fold change (FC) was calculated to determine the differential expression of the samples. DISCUSSION: The transcription profiles of the 10 candidate genes were highly induced in HFLS-RA cells compared with HFLS cells. However, on treating the HFLS-RA cells with MTX, the transcription profiles of these genes were highly downregulated. The most significant expression FC difference between HFLS and HFLS-RA (treated and untreated) was observed with HSPA6, MMP1, MMP13, and TNFSF10 genes. CONCLUSIONS: The data from this study suggest the use of HSPA6, MMP1, MMP13, and TNFSF10 gene expression profiles as potential diagnostic biomarkers. In addition, these gene profiles can help in predicting the therapeutic efficacy of MTX.
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spelling pubmed-61535282018-09-27 Identifying Reliable Diagnostic/Predictive Biomarkers for Rheumatoid Arthritis Shervington, Leroy Darekar, Ashish Shaikh, Murassa Mathews, Roshini Shervington, Amal Biomark Insights Original Research INTRODUCTION AND OBJECTIVE: Elevated C-reactive protein is usually a good indicator of rheumatoid arthritis (RA); however, there are limitations that compromise its specificity and therefore there is an urgent need to identify more reliable diagnostic biomarkers to detect early stages of RA. In addition, identifying the correct therapeutic biomarker for the treatment of RA using methotrexate (MTX) would greatly increase the benefits experienced by the patients. MATERIALS AND METHODS: Primary normal synoviocytes human fibroblast-like synoviocytes (HFLS) and its phenotype rheumatic HFLS-RA cells were chosen for this study. The HFLS-RA–untreated and MTX-treated cells were subjected to microarray analysis. RESULTS: Microarray data identified 74 differentially expressed genes. These genes were mapped against an RA inflammatory pathway, shortlisting 10 candidate genes. Gene expression profiling of the 10 genes were studied. Fold change (FC) was calculated to determine the differential expression of the samples. DISCUSSION: The transcription profiles of the 10 candidate genes were highly induced in HFLS-RA cells compared with HFLS cells. However, on treating the HFLS-RA cells with MTX, the transcription profiles of these genes were highly downregulated. The most significant expression FC difference between HFLS and HFLS-RA (treated and untreated) was observed with HSPA6, MMP1, MMP13, and TNFSF10 genes. CONCLUSIONS: The data from this study suggest the use of HSPA6, MMP1, MMP13, and TNFSF10 gene expression profiles as potential diagnostic biomarkers. In addition, these gene profiles can help in predicting the therapeutic efficacy of MTX. SAGE Publications 2018-09-24 /pmc/articles/PMC6153528/ /pubmed/30262983 http://dx.doi.org/10.1177/1177271918801005 Text en © The Author(s) 2018 http://www.creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Original Research
Shervington, Leroy
Darekar, Ashish
Shaikh, Murassa
Mathews, Roshini
Shervington, Amal
Identifying Reliable Diagnostic/Predictive Biomarkers for Rheumatoid Arthritis
title Identifying Reliable Diagnostic/Predictive Biomarkers for Rheumatoid Arthritis
title_full Identifying Reliable Diagnostic/Predictive Biomarkers for Rheumatoid Arthritis
title_fullStr Identifying Reliable Diagnostic/Predictive Biomarkers for Rheumatoid Arthritis
title_full_unstemmed Identifying Reliable Diagnostic/Predictive Biomarkers for Rheumatoid Arthritis
title_short Identifying Reliable Diagnostic/Predictive Biomarkers for Rheumatoid Arthritis
title_sort identifying reliable diagnostic/predictive biomarkers for rheumatoid arthritis
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6153528/
https://www.ncbi.nlm.nih.gov/pubmed/30262983
http://dx.doi.org/10.1177/1177271918801005
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