Up regulation of monocyte chemoattractant protein-1 expression in anti-citrulline antibody and immunoglobulin M rheumatoid factor positive subjects precedes onset of inflammatory response and development of overt rheumatoid arthritis.
OBJECTIVE
To analyse the inflammatory mediators, including monocyte chemoattractant protein-1 (MCP-1), in blood samples donated years before onset of rheumatoid arthritis. Previously, it has been shown in these individuals that antibodies against cyclic citrullinated peptide (anti-CCP) detectable years before the onset of symptoms have a high predictive value for development of rheumatoid arthritis.


METHODS
A nested case-control study was performed: patients with rheumatoid arthritis were identified from among blood donors antedating onset by a median of three years (pre-patients, n = 92); four matched controls were selected randomly for each pre-patient. Plasma were analysed for secretory phospholipase A2 (sPLA2) and MCP-1 using ELISA, for high-sensitivity C reactive protein (hsCRP) using the chemiluminescence method and for interleukin-6 using a sensitive bioassay.


RESULTS
When the results were stratified for the presence of anti-CCP antibodies and immunoglobulin M-rheumatoid factor (IgM-RF), only MCP-1 levels were found to be significantly raised in patients with anti-CCP and IgM-RF compared with controls.


CONCLUSIONS
Levels of MCP-1 were significantly increased in the plasma of patients having anti-CCP antibodies or IgM-RF and who later developed rheumatoid arthritis. These findings indicate up regulation of chemotactic activity for leucocytes before the development of rheumatoid arthritis.
Rantapää-Dahlqvist
S
S
Department of Rheumatology, University Hospital, SE-901 85 Umeå, Sweden. Solbritt.Rantapaa.Dahlqvist@medicin.umu.se
Boman
K
K
Tarkowski
A
A
Hallmans
G
G
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood*; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D001782:Blood Donors; D002097:C-Reactive Protein / Q000032:analysis; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000097:blood*; D016009:Chi-Square Distribution; D002956:Citrulline / Q000276:immunology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood; D008297:Male; D008875:Middle Aged; D012217:Rheumatoid Factor / Q000097:blood; D012720:Severity of Illness Index; D013997:Time Factors; D015854:Up-Regulation
D001323:Autoantibodies; D015415:Biomarkers; D018932:Chemokine CCL2; D007075:Immunoglobulin M; D002956:Citrulline; D002097:C-Reactive Protein; D012217:Rheumatoid Factor