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.

• Authors: 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
• Journal: Osteoarthritis and cartilage (Osteoarthritis Cartilage) Vol. 20 Issue 8 Pg. 854-62 (Aug 2012) ISSN: 1522-9653 [Electronic] England
• PMID: 22595227 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Antirheumatic Agents
• Atsttrin fusion protein
• Cartilage Oligomeric Matrix Protein
• Extracellular Matrix Proteins
• Glycoproteins
• Matn1 protein, mouse
• Matrilin Proteins
• Recombinant Fusion Proteins
• TSP5 protein, human
• Tumor Necrosis Factor-alpha
• Methotrexate

Topics

• Adolescent
• Adult
• Animals
• Antirheumatic Agents (pharmacology)
• Arthritis, Experimental (metabolism)
• Arthritis, Rheumatoid (metabolism)
• Cartilage Oligomeric Matrix Protein
• Case-Control Studies
• Enzyme-Linked Immunosorbent Assay (methods)
• Extracellular Matrix Proteins (drug effects, metabolism)
• Female
• Glycoproteins (drug effects, metabolism)
• Humans
• Male
• Matrilin Proteins
• Methotrexate (pharmacology)
• Mice
• Mice, Transgenic
• Middle Aged
• Osteoarthritis (metabolism)
• Recombinant Fusion Proteins (pharmacology)
• Synovial Fluid (metabolism)
• Tumor Necrosis Factor-alpha (pharmacology)
• Young Adult