Enhanced COMP catabolism detected in serum of patients with arthritis and animal disease models through a novel capture ELISA

Y. Lai, X. P. Yu, Y. Zhang, Q. Tian, H. Song, M. T. Mucignat, R. Perris, J. Samuels, S. Krasnokutsky, M. Attur, J. D. Greenberg, S. B. Abramson, P. E. Di Cesare, C. J. Liu

Research output: Contribution to journalArticle

Abstract

Objective: The study aimed determining whether assessment of cartilage oligomeric matrix protein (COMP) degradation products could serve as a serological disease course and therapeutic response predictor in arthritis. Methods: We generated a panel of monoclonal antibodies against COMP fragments and developed a novel capture enzyme-linked immunosorbent assay (ELISA) for detecting COMP fragments in patients with osteoarthritis (OA) and rheumatoid arthritis (RA). This test was also used to monitor COMP fragments in surgically-induced OA, collagen-induced arthritis (CIA), and tumor necrosis factor (TNF) transgenic animal models. Results: Compared with a commercial COMP ELISA kit that detected no significant difference in COMP levels between OA and control groups, a significant increase of the COMP fragments were noted in the serum of OA patients assayed by this newly established ELISA. In addition, serum COMP fragment levels were well correlated with severity in OA patients and the progression of surgically-induced OA in murine models. Furthermore, the serum levels of COMP fragments in RA patients, mice with CIA, and TNF transgenic mice were significantly higher when compared with their controls. Interestingly, treatment with TNFα inhibitors and methotrexate led to a significant decrease of serum COMP fragments in RA patients. Additionally, administration of Atsttrin [Tang, et al., Science 2011;332(6028):478] also resulted in a significant reduction in COMP fragments in arthritis mice models. Conclusion: A novel sandwich ELISA is capable of reproducibly measuring serum COMP fragments in both arthritic patients and rodent arthritis models. This test also provides a valuable means to utilize serum COMP fragments for monitoring the effects of interventions in arthritis.

Original languageEnglish
Pages (from-to)854-862
Number of pages9
JournalOsteoarthritis and Cartilage
Volume20
Issue number8
DOIs
Publication statusPublished - Aug 2012

Fingerprint

Cartilage Oligomeric Matrix Protein
Animal Disease Models
Cartilage
Arthritis
Assays
Animals
Enzymes
Enzyme-Linked Immunosorbent Assay
Proteins
Serum
Osteoarthritis
Blood Proteins
Rheumatoid Arthritis
Experimental Arthritis
Tumor Necrosis Factor-alpha
Collagen
Immunosorbents
Genetically Modified Animals
Monoclonal antibodies

Keywords

  • Arthritis
  • COMP
  • Degradative fragments
  • ECM1
  • ELISA

ASJC Scopus subject areas

  • Biomedical Engineering
  • Orthopedics and Sports Medicine
  • Rheumatology

Cite this

Enhanced COMP catabolism detected in serum of patients with arthritis and animal disease models through a novel capture ELISA. / Lai, Y.; Yu, X. P.; Zhang, Y.; Tian, Q.; Song, H.; Mucignat, M. T.; Perris, R.; Samuels, J.; Krasnokutsky, S.; Attur, M.; Greenberg, J. D.; Abramson, S. B.; Di Cesare, P. E.; Liu, C. J.

In: Osteoarthritis and Cartilage, Vol. 20, No. 8, 08.2012, p. 854-862.

Research output: Contribution to journalArticle

Lai, Y, Yu, XP, Zhang, Y, Tian, Q, Song, H, Mucignat, MT, Perris, R, Samuels, J, Krasnokutsky, S, Attur, M, Greenberg, JD, Abramson, SB, Di Cesare, PE & Liu, CJ 2012, 'Enhanced COMP catabolism detected in serum of patients with arthritis and animal disease models through a novel capture ELISA', Osteoarthritis and Cartilage, vol. 20, no. 8, pp. 854-862. https://doi.org/10.1016/j.joca.2012.05.003
Lai, Y. ; Yu, X. P. ; Zhang, Y. ; Tian, Q. ; Song, H. ; Mucignat, M. T. ; Perris, R. ; Samuels, J. ; Krasnokutsky, S. ; Attur, M. ; Greenberg, J. D. ; Abramson, S. B. ; Di Cesare, P. E. ; Liu, C. J. / Enhanced COMP catabolism detected in serum of patients with arthritis and animal disease models through a novel capture ELISA. In: Osteoarthritis and Cartilage. 2012 ; Vol. 20, No. 8. pp. 854-862.
@article{3439f8411b064628bf3ce53588975b58,
title = "Enhanced COMP catabolism detected in serum of patients with arthritis and animal disease models through a novel capture ELISA",
abstract = "Objective: The study aimed determining whether assessment of cartilage oligomeric matrix protein (COMP) degradation products could serve as a serological disease course and therapeutic response predictor in arthritis. Methods: We generated a panel of monoclonal antibodies against COMP fragments and developed a novel capture enzyme-linked immunosorbent assay (ELISA) for detecting COMP fragments in patients with osteoarthritis (OA) and rheumatoid arthritis (RA). This test was also used to monitor COMP fragments in surgically-induced OA, collagen-induced arthritis (CIA), and tumor necrosis factor (TNF) transgenic animal models. Results: Compared with a commercial COMP ELISA kit that detected no significant difference in COMP levels between OA and control groups, a significant increase of the COMP fragments were noted in the serum of OA patients assayed by this newly established ELISA. In addition, serum COMP fragment levels were well correlated with severity in OA patients and the progression of surgically-induced OA in murine models. Furthermore, the serum levels of COMP fragments in RA patients, mice with CIA, and TNF transgenic mice were significantly higher when compared with their controls. Interestingly, treatment with TNFα inhibitors and methotrexate led to a significant decrease of serum COMP fragments in RA patients. Additionally, administration of Atsttrin [Tang, et al., Science 2011;332(6028):478] also resulted in a significant reduction in COMP fragments in arthritis mice models. Conclusion: A novel sandwich ELISA is capable of reproducibly measuring serum COMP fragments in both arthritic patients and rodent arthritis models. This test also provides a valuable means to utilize serum COMP fragments for monitoring the effects of interventions in arthritis.",
keywords = "Arthritis, COMP, Degradative fragments, ECM1, ELISA",
author = "Y. Lai and Yu, {X. P.} and Y. Zhang and Q. Tian and H. Song and Mucignat, {M. T.} and R. Perris and J. Samuels and S. Krasnokutsky and M. Attur and Greenberg, {J. D.} and Abramson, {S. B.} and {Di Cesare}, {P. E.} and Liu, {C. J.}",
year = "2012",
month = "8",
doi = "10.1016/j.joca.2012.05.003",
language = "English",
volume = "20",
pages = "854--862",
journal = "Osteoarthritis and Cartilage",
issn = "1063-4584",
publisher = "W.B. Saunders Ltd",
number = "8",

}

TY - JOUR

T1 - Enhanced COMP catabolism detected in serum of patients with arthritis and animal disease models through a novel capture ELISA

AU - Lai, Y.

AU - Yu, X. P.

AU - Zhang, Y.

AU - Tian, Q.

AU - Song, H.

AU - Mucignat, M. T.

AU - Perris, R.

AU - Samuels, J.

AU - Krasnokutsky, S.

AU - Attur, M.

AU - Greenberg, J. D.

AU - Abramson, S. B.

AU - Di Cesare, P. E.

AU - Liu, C. J.

PY - 2012/8

Y1 - 2012/8

N2 - Objective: The study aimed determining whether assessment of cartilage oligomeric matrix protein (COMP) degradation products could serve as a serological disease course and therapeutic response predictor in arthritis. Methods: We generated a panel of monoclonal antibodies against COMP fragments and developed a novel capture enzyme-linked immunosorbent assay (ELISA) for detecting COMP fragments in patients with osteoarthritis (OA) and rheumatoid arthritis (RA). This test was also used to monitor COMP fragments in surgically-induced OA, collagen-induced arthritis (CIA), and tumor necrosis factor (TNF) transgenic animal models. Results: Compared with a commercial COMP ELISA kit that detected no significant difference in COMP levels between OA and control groups, a significant increase of the COMP fragments were noted in the serum of OA patients assayed by this newly established ELISA. In addition, serum COMP fragment levels were well correlated with severity in OA patients and the progression of surgically-induced OA in murine models. Furthermore, the serum levels of COMP fragments in RA patients, mice with CIA, and TNF transgenic mice were significantly higher when compared with their controls. Interestingly, treatment with TNFα inhibitors and methotrexate led to a significant decrease of serum COMP fragments in RA patients. Additionally, administration of Atsttrin [Tang, et al., Science 2011;332(6028):478] also resulted in a significant reduction in COMP fragments in arthritis mice models. Conclusion: A novel sandwich ELISA is capable of reproducibly measuring serum COMP fragments in both arthritic patients and rodent arthritis models. This test also provides a valuable means to utilize serum COMP fragments for monitoring the effects of interventions in arthritis.

AB - Objective: The study aimed determining whether assessment of cartilage oligomeric matrix protein (COMP) degradation products could serve as a serological disease course and therapeutic response predictor in arthritis. Methods: We generated a panel of monoclonal antibodies against COMP fragments and developed a novel capture enzyme-linked immunosorbent assay (ELISA) for detecting COMP fragments in patients with osteoarthritis (OA) and rheumatoid arthritis (RA). This test was also used to monitor COMP fragments in surgically-induced OA, collagen-induced arthritis (CIA), and tumor necrosis factor (TNF) transgenic animal models. Results: Compared with a commercial COMP ELISA kit that detected no significant difference in COMP levels between OA and control groups, a significant increase of the COMP fragments were noted in the serum of OA patients assayed by this newly established ELISA. In addition, serum COMP fragment levels were well correlated with severity in OA patients and the progression of surgically-induced OA in murine models. Furthermore, the serum levels of COMP fragments in RA patients, mice with CIA, and TNF transgenic mice were significantly higher when compared with their controls. Interestingly, treatment with TNFα inhibitors and methotrexate led to a significant decrease of serum COMP fragments in RA patients. Additionally, administration of Atsttrin [Tang, et al., Science 2011;332(6028):478] also resulted in a significant reduction in COMP fragments in arthritis mice models. Conclusion: A novel sandwich ELISA is capable of reproducibly measuring serum COMP fragments in both arthritic patients and rodent arthritis models. This test also provides a valuable means to utilize serum COMP fragments for monitoring the effects of interventions in arthritis.

KW - Arthritis

KW - COMP

KW - Degradative fragments

KW - ECM1

KW - ELISA

UR - http://www.scopus.com/inward/record.url?scp=84862986533&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84862986533&partnerID=8YFLogxK

U2 - 10.1016/j.joca.2012.05.003

DO - 10.1016/j.joca.2012.05.003

M3 - Article

C2 - 22595227

AN - SCOPUS:84862986533

VL - 20

SP - 854

EP - 862

JO - Osteoarthritis and Cartilage

JF - Osteoarthritis and Cartilage

SN - 1063-4584

IS - 8

ER -