Messenger ribonucleic acid expression profile in peripheral blood cells from RA patients following treatment with an anti-TNF-α monoclonal antibody, infliximab

N. Sekiguchi, S. Kawauchi, T. Furuya, N. Inaba, K. Matsuda, S. Ando, M. Ogasawara, H. Aburatani, H. Kameda, K. Amano, T. Abe, S. Ito, Tsutomu Takeuchi

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

Objectives. We monitored the mRNA expression profiles of peripheral blood cells during treatment with a TNF-α inhibitor, infliximab, in patients with RA. Using a DNA microarray analysis, we demonstrated a unique set of genes, with distinct baseline and post-treatment changes in expression between responders and non-responders to infliximab treatment. Methods. Using a customized low-density cDNA microarray with 747 genes and a reliable data collection system, we monitored the mRNA expression profiles of whole blood cells from 18 RA patients before and after the infusion of infliximab for up to 22 weeks. The clinical response to treatment with infliximab was determined using the ACR response criteria, the disease activity score of 28 joints (DAS28), and individual clinical parameters. The patients were classified as responders or non-responders based on their ACR50% response at 22 weeks. Results. Approximately 15% of the total genes were found to exhibit a >1.5-fold change, compared with their reference values, at one or more time points during the 22 weeks of infliximab therapy. The expression of inflammatory genes, such as IFN-related genes, was strongly correlated with the serum level of CRP and the DAS28. The increased expression of inflammatory genes in responders was normalized within 2 weeks and then remained at a normal level during the treatment period. In contrast, in the non-responders, the elevated expression at baseline, although it was significantly decreased at 2 weeks, returned to the baseline level after 14 weeks. In addition to inflammatory genes, we identified several groups of genes with distinct differences in expression between the responders and non-responders. Conclusions. Our results suggest that a customized low-density microarray is useful for monitoring mRNA expression profiles in peripheral blood cells, enabling us to identify a unique set of genes with differentially regulated expressions in responders and non-responders to a TNF inhibitor among patients with RA.

Original languageEnglish
Pages (from-to)780-788
Number of pages9
JournalRheumatology
Volume47
Issue number6
DOIs
Publication statusPublished - 2008 Jun
Externally publishedYes

Fingerprint

Blood Cells
Monoclonal Antibodies
RNA
Genes
Oligonucleotide Array Sequence Analysis
Messenger RNA
Therapeutics
Joints
Gene Expression
Microarray Analysis
Infliximab
Information Systems
Reference Values
Serum

Keywords

  • Biological products
  • Infliximab
  • Interferons
  • Messenger ribonucleic acid
  • Oligonucleotide array sequence analysis
  • Reverse transcriptase-polymerase chain reaction
  • Rheumatoid arthritis
  • Tumour necrosis factor

ASJC Scopus subject areas

  • Neuroscience(all)
  • Rheumatology

Cite this

Messenger ribonucleic acid expression profile in peripheral blood cells from RA patients following treatment with an anti-TNF-α monoclonal antibody, infliximab. / Sekiguchi, N.; Kawauchi, S.; Furuya, T.; Inaba, N.; Matsuda, K.; Ando, S.; Ogasawara, M.; Aburatani, H.; Kameda, H.; Amano, K.; Abe, T.; Ito, S.; Takeuchi, Tsutomu.

In: Rheumatology, Vol. 47, No. 6, 06.2008, p. 780-788.

Research output: Contribution to journalArticle

Sekiguchi, N, Kawauchi, S, Furuya, T, Inaba, N, Matsuda, K, Ando, S, Ogasawara, M, Aburatani, H, Kameda, H, Amano, K, Abe, T, Ito, S & Takeuchi, T 2008, 'Messenger ribonucleic acid expression profile in peripheral blood cells from RA patients following treatment with an anti-TNF-α monoclonal antibody, infliximab', Rheumatology, vol. 47, no. 6, pp. 780-788. https://doi.org/10.1093/rheumatology/ken083
Sekiguchi, N. ; Kawauchi, S. ; Furuya, T. ; Inaba, N. ; Matsuda, K. ; Ando, S. ; Ogasawara, M. ; Aburatani, H. ; Kameda, H. ; Amano, K. ; Abe, T. ; Ito, S. ; Takeuchi, Tsutomu. / Messenger ribonucleic acid expression profile in peripheral blood cells from RA patients following treatment with an anti-TNF-α monoclonal antibody, infliximab. In: Rheumatology. 2008 ; Vol. 47, No. 6. pp. 780-788.
@article{08840756f73e45d48b5cb59f1100c2a9,
title = "Messenger ribonucleic acid expression profile in peripheral blood cells from RA patients following treatment with an anti-TNF-α monoclonal antibody, infliximab",
abstract = "Objectives. We monitored the mRNA expression profiles of peripheral blood cells during treatment with a TNF-α inhibitor, infliximab, in patients with RA. Using a DNA microarray analysis, we demonstrated a unique set of genes, with distinct baseline and post-treatment changes in expression between responders and non-responders to infliximab treatment. Methods. Using a customized low-density cDNA microarray with 747 genes and a reliable data collection system, we monitored the mRNA expression profiles of whole blood cells from 18 RA patients before and after the infusion of infliximab for up to 22 weeks. The clinical response to treatment with infliximab was determined using the ACR response criteria, the disease activity score of 28 joints (DAS28), and individual clinical parameters. The patients were classified as responders or non-responders based on their ACR50{\%} response at 22 weeks. Results. Approximately 15{\%} of the total genes were found to exhibit a >1.5-fold change, compared with their reference values, at one or more time points during the 22 weeks of infliximab therapy. The expression of inflammatory genes, such as IFN-related genes, was strongly correlated with the serum level of CRP and the DAS28. The increased expression of inflammatory genes in responders was normalized within 2 weeks and then remained at a normal level during the treatment period. In contrast, in the non-responders, the elevated expression at baseline, although it was significantly decreased at 2 weeks, returned to the baseline level after 14 weeks. In addition to inflammatory genes, we identified several groups of genes with distinct differences in expression between the responders and non-responders. Conclusions. Our results suggest that a customized low-density microarray is useful for monitoring mRNA expression profiles in peripheral blood cells, enabling us to identify a unique set of genes with differentially regulated expressions in responders and non-responders to a TNF inhibitor among patients with RA.",
keywords = "Biological products, Infliximab, Interferons, Messenger ribonucleic acid, Oligonucleotide array sequence analysis, Reverse transcriptase-polymerase chain reaction, Rheumatoid arthritis, Tumour necrosis factor",
author = "N. Sekiguchi and S. Kawauchi and T. Furuya and N. Inaba and K. Matsuda and S. Ando and M. Ogasawara and H. Aburatani and H. Kameda and K. Amano and T. Abe and S. Ito and Tsutomu Takeuchi",
year = "2008",
month = "6",
doi = "10.1093/rheumatology/ken083",
language = "English",
volume = "47",
pages = "780--788",
journal = "Rheumatology (United Kingdom)",
issn = "1462-0324",
publisher = "Oxford University Press",
number = "6",

}

TY - JOUR

T1 - Messenger ribonucleic acid expression profile in peripheral blood cells from RA patients following treatment with an anti-TNF-α monoclonal antibody, infliximab

AU - Sekiguchi, N.

AU - Kawauchi, S.

AU - Furuya, T.

AU - Inaba, N.

AU - Matsuda, K.

AU - Ando, S.

AU - Ogasawara, M.

AU - Aburatani, H.

AU - Kameda, H.

AU - Amano, K.

AU - Abe, T.

AU - Ito, S.

AU - Takeuchi, Tsutomu

PY - 2008/6

Y1 - 2008/6

N2 - Objectives. We monitored the mRNA expression profiles of peripheral blood cells during treatment with a TNF-α inhibitor, infliximab, in patients with RA. Using a DNA microarray analysis, we demonstrated a unique set of genes, with distinct baseline and post-treatment changes in expression between responders and non-responders to infliximab treatment. Methods. Using a customized low-density cDNA microarray with 747 genes and a reliable data collection system, we monitored the mRNA expression profiles of whole blood cells from 18 RA patients before and after the infusion of infliximab for up to 22 weeks. The clinical response to treatment with infliximab was determined using the ACR response criteria, the disease activity score of 28 joints (DAS28), and individual clinical parameters. The patients were classified as responders or non-responders based on their ACR50% response at 22 weeks. Results. Approximately 15% of the total genes were found to exhibit a >1.5-fold change, compared with their reference values, at one or more time points during the 22 weeks of infliximab therapy. The expression of inflammatory genes, such as IFN-related genes, was strongly correlated with the serum level of CRP and the DAS28. The increased expression of inflammatory genes in responders was normalized within 2 weeks and then remained at a normal level during the treatment period. In contrast, in the non-responders, the elevated expression at baseline, although it was significantly decreased at 2 weeks, returned to the baseline level after 14 weeks. In addition to inflammatory genes, we identified several groups of genes with distinct differences in expression between the responders and non-responders. Conclusions. Our results suggest that a customized low-density microarray is useful for monitoring mRNA expression profiles in peripheral blood cells, enabling us to identify a unique set of genes with differentially regulated expressions in responders and non-responders to a TNF inhibitor among patients with RA.

AB - Objectives. We monitored the mRNA expression profiles of peripheral blood cells during treatment with a TNF-α inhibitor, infliximab, in patients with RA. Using a DNA microarray analysis, we demonstrated a unique set of genes, with distinct baseline and post-treatment changes in expression between responders and non-responders to infliximab treatment. Methods. Using a customized low-density cDNA microarray with 747 genes and a reliable data collection system, we monitored the mRNA expression profiles of whole blood cells from 18 RA patients before and after the infusion of infliximab for up to 22 weeks. The clinical response to treatment with infliximab was determined using the ACR response criteria, the disease activity score of 28 joints (DAS28), and individual clinical parameters. The patients were classified as responders or non-responders based on their ACR50% response at 22 weeks. Results. Approximately 15% of the total genes were found to exhibit a >1.5-fold change, compared with their reference values, at one or more time points during the 22 weeks of infliximab therapy. The expression of inflammatory genes, such as IFN-related genes, was strongly correlated with the serum level of CRP and the DAS28. The increased expression of inflammatory genes in responders was normalized within 2 weeks and then remained at a normal level during the treatment period. In contrast, in the non-responders, the elevated expression at baseline, although it was significantly decreased at 2 weeks, returned to the baseline level after 14 weeks. In addition to inflammatory genes, we identified several groups of genes with distinct differences in expression between the responders and non-responders. Conclusions. Our results suggest that a customized low-density microarray is useful for monitoring mRNA expression profiles in peripheral blood cells, enabling us to identify a unique set of genes with differentially regulated expressions in responders and non-responders to a TNF inhibitor among patients with RA.

KW - Biological products

KW - Infliximab

KW - Interferons

KW - Messenger ribonucleic acid

KW - Oligonucleotide array sequence analysis

KW - Reverse transcriptase-polymerase chain reaction

KW - Rheumatoid arthritis

KW - Tumour necrosis factor

UR - http://www.scopus.com/inward/record.url?scp=44849130695&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=44849130695&partnerID=8YFLogxK

U2 - 10.1093/rheumatology/ken083

DO - 10.1093/rheumatology/ken083

M3 - Article

VL - 47

SP - 780

EP - 788

JO - Rheumatology (United Kingdom)

JF - Rheumatology (United Kingdom)

SN - 1462-0324

IS - 6

ER -