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

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 au...

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Published in:PloS one 2015-07, Vol.10 (7), p.e0133669-e0133669
Main Authors: de Hair, Maria J H, Leclerc, Patrick, Newsum, Elize C, Maijer, Karen I, van de Sande, Marleen G H, Ramwadhdoebe, Tamara H, van Schaardenburg, Dirkjan, van Baarsen, Lisa G M, Korotkova, Marina, Gerlag, Danielle M, Tak, Paul-Peter, Jakobsson, Per-Johan
Format: Article
Language:English
Subjects:
Adult
Antibodies
Arthralgia
Arthralgia - metabolism
Arthralgia - pathology
Arthritis
Arthritis, Rheumatoid - metabolism
Arthritis, Rheumatoid - pathology
Arthroscopy
Autoantibodies
Autoantibodies - metabolism
Biopsy
Citrulline
Cyclooxygenase 1 - metabolism
Cyclooxygenase 2 - metabolism
Cyclooxygenase-1
Dinoprostone - metabolism
Disease Progression
Enzymes
Etiology
Female
Genetics
Humans
Hydroxyprostaglandin Dehydrogenases - metabolism
Immunoglobulin M
Immunohistochemistry
Immunology
Inflammation - metabolism
Inflammation - pathology
Inflammatory diseases
Intramolecular Oxidoreductases - metabolism
Male
Medicin och hälsovetenskap
Middle Aged
Nonsteroidal anti-inflammatory drugs
Pain
Pain perception
Patients
Peptides, Cyclic - metabolism
Prospective Studies
Prostaglandin E2
Prostaglandin-E synthase
Prostaglandin-E Synthases
Rheumatic diseases
Rheumatoid arthritis
Rheumatoid factor
Rheumatoid Factor - metabolism
Rheumatology
Risk
Spondylarthritis - metabolism
Spondylarthritis - pathology
Synovial Membrane - metabolism
Synovial Membrane - pathology
Synovium
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Summary: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. 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). 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. 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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0133669