Differences in the profiles of circulating levels of soluble tumor necrosis factor receptors and interleukin 1 receptor antagonist reflect the heterogeneity of the subgroups of juvenile rheumatoid arthritis.
OBJECTIVE
To determine whether levels of soluble tumor necrosis factor receptor 55 (sTNFR55), sTNFR75, and interleukin 1 receptor antagonist (IL-1Ra) can differentiate different subtypes of juvenile rheumatoid arthritis (JRA), and to determine if the levels of these proteins correlate with disease activity.


METHODS
Serum sTNFR (55 and 75) and IL-1Ra levels were measured by ELISA in 34 patients with JRA and these values were correlated with disease subtype and activity.


RESULTS
Serum sTNFR55 levels were significantly elevated in patients with systemic onset JRA (SoJRA) (mean +/- 2 SD, 2.9 +/- 1.8 ng/ml) (p < or = 0.05) compared to rheumatoid factor positive (RF+) polyarticular JRA (2.1 +/- 0.6), RF-polyarticular JRA (1.5 +/- 0.6), and pauciarticular JRA (1.4 +/- 0.4). There was a trend for elevation of sTNFR75 levels in patients with SoJRA compared to other subtypes (p = 0.08). More patients had elevated levels of sTNFR75 than sTNFR55 (15 vs 7). This was true for all subsets (SoJRA 7 vs 5; polyarticular JRA 4 vs 2; and pauciarticular JRA 4 vs 0). In contrast to sTNFR, IL-1Ra levels were significantly elevated in RF+ polyarticular JRA compared to the other subgroups (p < or = 0.001). We found statistically significant Pearson correlations between (1) sTNFR75 and hemoglobin concentration: and (2) IL-1Ra and number of active joints and number of joints with effusions.


CONCLUSIONS
The increased serum level of sTNF receptors in SoJRA suggests that TNF is likely more important than IL-1 in systemic inflammation and in particular in SoJRA. Conversely, IL-1 is likely more important in the inflammatory arthritis of JRA and in particular in the pathogenesis of RF+ polyarticular JRA. Our results suggest that cytokines have differing roles in JRA subtypes and likely reflect JRA subtype heterogeneity.
Muzaffer
Mohammed A
MA
Division of Rheumatology, Hospital for Sick Children, Toronto, Ontario, Canada.
Dayer
Jean-Michel
JM
Feldman
Brian M
BM
Pruzanski
Waldemar
W
Roux-Lombard
Pascale
P
Schneider
Rayfel
R
Laxer
Ronald M
RM
Silverman
Earl D
ED
D000328:Adult; D015703:Antigens, CD / Q000097:blood* / Q000276:immunology; D001171:Arthritis, Juvenile / Q000097:blood* / Q000175:diagnosis / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006454:Hemoglobins; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D008297:Male; D011237:Predictive Value of Tests; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood* / Q000276:immunology; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D012720:Severity of Illness Index; D012795:Sialoglycoproteins / Q000097:blood* / Q000276:immunology; D012995:Solubility
D015703:Antigens, CD; D006454:Hemoglobins; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D012795:Sialoglycoproteins