Synovial fluid RANKL and matrix metalloproteinase levels in enthesitis related arthritis subtype of juvenile idiopathic arthritis.
In chronic arthritis cartilage and bone destruction occur as a consequence of synovial inflammation. It is mainly mediated by matrix metalloproteinases and RANKL-OPG pathways. Data on synovial fluid levels of these mediators in enthesitis related arthritis subtype (ERA) of JIA are not available. MMP-1, MMP-3, TIMP, sRANKL and OPG levels were measured in synovial fluid from patients with ERA and compared with other arthritides, polyarticular (Poly) JIA, RA and osteoarthritis (OA). sRANKL was detectable in 25/41 of ERA patients, 4/16 of Poly JIA patients. Median SF sRANKL level in patients with ERA was higher as compared to OA (p < 0.001) and poly JIA (p < 0.05) but were comparable to RA. The median OPG level in ERA was lower as compared to OA (p < 0.001), comparable to RA but was higher than poly JIA (p < 0.001). sRANKL/OPG ratio was significantly higher in ERA and Poly JIA compared to OA (p < 0.0001, p < 0.0001 respectively). The median MMP3 levels in ERA (74 microg/ml) was lower as compared to poly JIA (410 microg/ml; p < 0.0001) and RA (340 ug/ml; p < 0.0001) but was comparable to OA (107 microg/ml). The median level of ProMMP1 in ERA (0.70 microg/ml) was lower as compared to RA (2.9 microg/ml; p < 0.0001) and poly JIA but was elevated as compared to OA patients (0.1 microg/ml; p < 0.0001). TIMP1 levels in ERA were higher than poly JIA and RA patients. MMP3/TIMP1 ratio was lower in ERA compared to polyarticular JIA patients (p < 0.05). Ours is the first study reporting elevated sRANKL and reduced OPG levels and elevated sRANKL/OPG ratio in SF of children with JIA resulting in a mileu associated with bone loss. In addition, ERA patients had lower MMP level as well as MMP/TIMP ratio as compared to poly JIA which may partly explain lesser degree of joint damage seen in ERA as compared to poly JIA.
Agarwal
Shilpi
S
Department of Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
Misra
Ramnath
R
Aggarwal
Amita
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D001171:Arthritis, Juvenile / Q000145:classification* / Q000378:metabolism*; D001172:Arthritis, Rheumatoid / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008875:Middle Aged; D010003:Osteoarthritis / Q000378:metabolism; D053244:Osteoprotegerin / Q000378:metabolism; D053245:RANK Ligand / Q000378:metabolism*; D013582:Synovial Fluid / Q000378:metabolism*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism
D053244:Osteoprotegerin; D053245:RANK Ligand; D019715:Tissue Inhibitor of Metalloproteinase-1; D020782:Matrix Metalloproteinases