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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

Baseline synovial expression of PGE2 pathway enzymes of early arthritis patients classified as RA, UA and SpA at 2 years follow-up.Representative immunohistochemical staining (A), Expression of mPGES-1 (B) and COX-1 (C) is increased in SpA patients. D) A trend towards increased expression of COX-2 is observed in SpA patients; values expressed as median (IQR) on a logaritmic scale; RA: rheumatoid arthritis; UA: unclassified arthritis; SpA: spondyloarthritis; mPGES-1: microsomal prostaglandin E synthase-1; COX: cyclooxygenase; IOD: integrated optical density.
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pone.0133669.g002: Baseline synovial expression of PGE2 pathway enzymes of early arthritis patients classified as RA, UA and SpA at 2 years follow-up.Representative immunohistochemical staining (A), Expression of mPGES-1 (B) and COX-1 (C) is increased in SpA patients. D) A trend towards increased expression of COX-2 is observed in SpA patients; values expressed as median (IQR) on a logaritmic scale; RA: rheumatoid arthritis; UA: unclassified arthritis; SpA: spondyloarthritis; mPGES-1: microsomal prostaglandin E synthase-1; COX: cyclooxygenase; IOD: integrated optical density.

Mentions: Expression of mPGES-1,COX-1 and COX-2 was significantly different between the three diagnostic groups (p = 0.005, p = 0.021 and p = 0.044, respectively) (Fig 2). Tukey’s post-hoc test revealed that expression of mPGES-1 and COX-1 was increased in SpA compared to RA patients (p = 0.005 and p = 0.025, respectively) and that COX-2 expression was higher in SpA than RA patients although not statistically significant (p = 0.102).


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)

Baseline synovial expression of PGE2 pathway enzymes of early arthritis patients classified as RA, UA and SpA at 2 years follow-up.Representative immunohistochemical staining (A), Expression of mPGES-1 (B) and COX-1 (C) is increased in SpA patients. D) A trend towards increased expression of COX-2 is observed in SpA patients; values expressed as median (IQR) on a logaritmic scale; RA: rheumatoid arthritis; UA: unclassified arthritis; SpA: spondyloarthritis; mPGES-1: microsomal prostaglandin E synthase-1; COX: cyclooxygenase; IOD: integrated optical density.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0133669.g002: Baseline synovial expression of PGE2 pathway enzymes of early arthritis patients classified as RA, UA and SpA at 2 years follow-up.Representative immunohistochemical staining (A), Expression of mPGES-1 (B) and COX-1 (C) is increased in SpA patients. D) A trend towards increased expression of COX-2 is observed in SpA patients; values expressed as median (IQR) on a logaritmic scale; RA: rheumatoid arthritis; UA: unclassified arthritis; SpA: spondyloarthritis; mPGES-1: microsomal prostaglandin E synthase-1; COX: cyclooxygenase; IOD: integrated optical density.
Mentions: Expression of mPGES-1,COX-1 and COX-2 was significantly different between the three diagnostic groups (p = 0.005, p = 0.021 and p = 0.044, respectively) (Fig 2). Tukey’s post-hoc test revealed that expression of mPGES-1 and COX-1 was increased in SpA compared to RA patients (p = 0.005 and p = 0.025, respectively) and that COX-2 expression was higher in SpA than RA patients although not statistically significant (p = 0.102).

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