Limits...
Expression of Prostaglandin E2 Enzymes in the Synovium of Arthralgia Patients at Risk of Developing Rheumatoid Arthritis and in Early Arthritis Patients.

de Hair MJ, Leclerc P, Newsum EC, Maijer KI, van de Sande MG, Ramwadhdoebe TH, van Schaardenburg D, van Baarsen LG, Korotkova M, Gerlag DM, Tak PP, Jakobsson PJ - PLoS ONE (2015)

Bottom Line: Expression levels at baseline were not associated with the development of arthritis after follow up (6 out of 19 autoantibody-positive individuals).However, in early SpA patients the expression levels of mPGES-1 and COX-1 were significantly increased compared to RA and UA patients.In contrast, in SpA, the PGE2 pathway may be inherently linked to the pathophysiology/etiology of the disease.

View Article: PubMed Central - PubMed

Affiliation: Division of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Amsterdam, the Netherlands.

ABSTRACT

Objective: Arthralgia may precede the development of synovial inflammation in autoantibody-positive individuals at risk of developing rheumatoid arthritis (RA). A major pathway involved in pain is the prostaglandin (PG) E2 pathway. We investigated this pathway in the synovium of individuals with RA-specific autoantibodies and in early arthritis patients.

Methods: Nineteen autoantibody-positive individuals (IgM-rheumatoid factor and/or anti-cyclic citrullinated peptide antibodies) with arthralgia (n=15) and/or a positive family history of RA (n=8), who had been prospectively followed for at least 2 years, were included. In addition, we included early arthritis patients (disease-modifying antirheumatic drug naïve) who after 2 years follow up fulfilled classification criteria for RA (n=63), spondyloarthritis (SpA; n=14), or had unclassified arthritis (UA; n=27). In all subjects we assessed pain and performed synovial biopsy sampling by mini-arthroscopy at baseline. Tissue sections were examined by immunohistochemistry to detect and quantify PGE2 pathway enzymes expression levels (mPGES-1; COX-1 and -2; 15-PGDH).

Results: In both study groups synovial expression of PGE2 enzymes was not clearly related to pain sensation. Expression levels at baseline were not associated with the development of arthritis after follow up (6 out of 19 autoantibody-positive individuals). However, in early SpA patients the expression levels of mPGES-1 and COX-1 were significantly increased compared to RA and UA patients.

Conclusion: Pain in autoantibody-positive individuals without synovial inflammation who are at risk of developing RA and in early arthritis patients may be regulated by pathways other than the PGE2 pathway or originate at sites other than the synovium. In contrast, in SpA, the PGE2 pathway may be inherently linked to the pathophysiology/etiology of the disease.

No MeSH data available.


Related in: MedlinePlus

Synovial expression of mPGES-1, COX-1, COX-2 and 15-PGDH in autoantibody-positive individuals at risk of developing RA.Panel (A): comparison of individuals with or without arthralgia in general. Panel (B): comparison of individuals with or without arthralgia in the biopsied joint, within the group of individuals with arthralgia only; values expressed as median (IQR). mPGES-1: microsomal prostaglandin E synthase-1; COX: cyclooxygenase, 15-PGDH: 15-hydroxy prostaglandin dehydrogenase.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4520525&req=5

pone.0133669.g001: Synovial expression of mPGES-1, COX-1, COX-2 and 15-PGDH in autoantibody-positive individuals at risk of developing RA.Panel (A): comparison of individuals with or without arthralgia in general. Panel (B): comparison of individuals with or without arthralgia in the biopsied joint, within the group of individuals with arthralgia only; values expressed as median (IQR). mPGES-1: microsomal prostaglandin E synthase-1; COX: cyclooxygenase, 15-PGDH: 15-hydroxy prostaglandin dehydrogenase.

Mentions: In 15 individuals with arthralgia compared to 4 individuals without arthralgia a trend towards higher expression of COX-1 was observed (p = 0.078) as well as COX-2 (p = 0.470) and 15-PGDH (p = 0.352) (Fig 1, panel A), which failed to reach statistical significance. Expression of PGE2 pathway enzymes did not correlate with pain scores (Table 2).


Expression of Prostaglandin E2 Enzymes in the Synovium of Arthralgia Patients at Risk of Developing Rheumatoid Arthritis and in Early Arthritis Patients.

de Hair MJ, Leclerc P, Newsum EC, Maijer KI, van de Sande MG, Ramwadhdoebe TH, van Schaardenburg D, van Baarsen LG, Korotkova M, Gerlag DM, Tak PP, Jakobsson PJ - PLoS ONE (2015)

Synovial expression of mPGES-1, COX-1, COX-2 and 15-PGDH in autoantibody-positive individuals at risk of developing RA.Panel (A): comparison of individuals with or without arthralgia in general. Panel (B): comparison of individuals with or without arthralgia in the biopsied joint, within the group of individuals with arthralgia only; values expressed as median (IQR). mPGES-1: microsomal prostaglandin E synthase-1; COX: cyclooxygenase, 15-PGDH: 15-hydroxy prostaglandin dehydrogenase.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4520525&req=5

pone.0133669.g001: Synovial expression of mPGES-1, COX-1, COX-2 and 15-PGDH in autoantibody-positive individuals at risk of developing RA.Panel (A): comparison of individuals with or without arthralgia in general. Panel (B): comparison of individuals with or without arthralgia in the biopsied joint, within the group of individuals with arthralgia only; values expressed as median (IQR). mPGES-1: microsomal prostaglandin E synthase-1; COX: cyclooxygenase, 15-PGDH: 15-hydroxy prostaglandin dehydrogenase.
Mentions: In 15 individuals with arthralgia compared to 4 individuals without arthralgia a trend towards higher expression of COX-1 was observed (p = 0.078) as well as COX-2 (p = 0.470) and 15-PGDH (p = 0.352) (Fig 1, panel A), which failed to reach statistical significance. Expression of PGE2 pathway enzymes did not correlate with pain scores (Table 2).

Bottom Line: Expression levels at baseline were not associated with the development of arthritis after follow up (6 out of 19 autoantibody-positive individuals).However, in early SpA patients the expression levels of mPGES-1 and COX-1 were significantly increased compared to RA and UA patients.In contrast, in SpA, the PGE2 pathway may be inherently linked to the pathophysiology/etiology of the disease.

View Article: PubMed Central - PubMed

Affiliation: Division of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Amsterdam, the Netherlands.

ABSTRACT

Objective: Arthralgia may precede the development of synovial inflammation in autoantibody-positive individuals at risk of developing rheumatoid arthritis (RA). A major pathway involved in pain is the prostaglandin (PG) E2 pathway. We investigated this pathway in the synovium of individuals with RA-specific autoantibodies and in early arthritis patients.

Methods: Nineteen autoantibody-positive individuals (IgM-rheumatoid factor and/or anti-cyclic citrullinated peptide antibodies) with arthralgia (n=15) and/or a positive family history of RA (n=8), who had been prospectively followed for at least 2 years, were included. In addition, we included early arthritis patients (disease-modifying antirheumatic drug naïve) who after 2 years follow up fulfilled classification criteria for RA (n=63), spondyloarthritis (SpA; n=14), or had unclassified arthritis (UA; n=27). In all subjects we assessed pain and performed synovial biopsy sampling by mini-arthroscopy at baseline. Tissue sections were examined by immunohistochemistry to detect and quantify PGE2 pathway enzymes expression levels (mPGES-1; COX-1 and -2; 15-PGDH).

Results: In both study groups synovial expression of PGE2 enzymes was not clearly related to pain sensation. Expression levels at baseline were not associated with the development of arthritis after follow up (6 out of 19 autoantibody-positive individuals). However, in early SpA patients the expression levels of mPGES-1 and COX-1 were significantly increased compared to RA and UA patients.

Conclusion: Pain in autoantibody-positive individuals without synovial inflammation who are at risk of developing RA and in early arthritis patients may be regulated by pathways other than the PGE2 pathway or originate at sites other than the synovium. In contrast, in SpA, the PGE2 pathway may be inherently linked to the pathophysiology/etiology of the disease.

No MeSH data available.


Related in: MedlinePlus