Ex vivo interleukin 1 receptor antagonist production on lipopolysaccharide stimulation is associated with rheumatoid arthritis and with joint damage.
OBJECTIVE
(1) To assess innate ex vivo production of interleukin 1beta (IL1beta) and interleukin 1 receptor antagonist (IL1Ra) in patients with recent-onset rheumatoid arthritis (RA) as compared with healthy controls; (2) to assess the association of ex vivo IL1beta and IL1Ra production with progression of joint damage in RA; (3) to determine whether differences in ex vivo IL1beta production are explained by distribution of the IL1beta single nucleotide polymorphism C-511T.


METHODS
Levels of IL1beta and IL1Ra (measured by ELISA after whole-blood stimulation with lipopolysaccharide) and distribution of IL1beta C-511T were compared in 76 patients with recent-onset RA who had received no disease-modifying antirheumatic drugs (DMARDs), and 63 healthy controls. ORs for RA based on ex vivo IL1beta and IL1Ra production were calculated. Association of ex vivo IL1beta and IL1Ra production with progression of joint damage (Sharp-van der Heijde score over 2 years) was determined by linear regression with correction for baseline characteristics.


RESULTS
Patients with recent-onset RA showed lower ex vivo IL1beta and higher ex vivo IL1Ra production than healthy controls (p<0.001), with ORs for RA of 2.4 (95% CI 1.2 to 4.9) for low IL1beta-producers and 7.6 (95% CI 3.2 to 18.0) for high IL1Ra-producers. High ex vivo IL1Ra production was associated with progression of joint damage (p = 0.01). The IL1beta C-511T genotype distribution was not significantly different between patients and controls.


CONCLUSIONS
Patients with recent-onset RA had decreased ex vivo IL1beta production and increased ex vivo IL1Ra production compared with controls. Ex vivo IL1Ra production is an independent predictor of progression of joint damage in recent-onset RA.
de Vries-Bouwstra
J K
JK
Department of Rheumatology, VU University Medical Center, Amsterdam, The Netherlands. jkdevriesbouwstra@lumc.nl
Goekoop-Ruiterman
Y P M
YP
Wesoly
J
J
Hulsmans
H J
HJ
de Craen
A J M
AJ
Breedveld
F C
FC
Dijkmans
B A C
BA
Allaart
C F
CF
Huizinga
T W J
TW
D000208:Acute Disease; D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000000981:diagnostic imaging / Q000276:immunology; D001175:Arthrography; D015415:Biomarkers / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D004812:Epidemiologic Methods; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000096:biosynthesis* / Q000097:blood; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D013268:Stimulation, Chemical
D015415:Biomarkers; D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D008070:Lipopolysaccharides