Research

Elevated serum levels of soluble CD154 in children with juvenile idiopathic arthritis

Sampath Prahalad¹ , Thomas B Martins² , Anne E Tebo^2,3 , April Whiting¹ , Bronte Clifford¹ , Andrew S Zeft¹ , Bernadette McNally¹ , John F Bohnsack¹ and Harry R Hill^1,2,3,4

¹Department of Pediatrics, University of Utah, Salt Lake City, UT, USA

²The Associated Regional and University Pathologists Institute for Clinical and Experimental Pathology, Salt Lake City, UT, USA

³Department of Pathology, University of Utah, Salt Lake City, UT, USA

⁴Department of Medicine, University of Utah, Salt Lake City, UT, USA

author email corresponding author email

Pediatric Rheumatology 2008, 6:8doi:10.1186/1546-0096-6-8

Published:	28 May 2008

Abstract

Objective

Cytokines play important roles in mediating inflammation in autoimmunity. Several cytokines are elevated in serum and synovial fluid samples from children with Juvenile Idiopathic Arthritis (JIA). Soluble CD154 (sCD154) is elevated in other autoimmune disorders, but has not been characterized in JIA. Our objectives were to determine if sCD154 is elevated in JIA, and to examine correlations between sCD154 and other inflammatory cytokines.

Methods

Serum from 77 children with JIA and 81 pediatric controls was analyzed for interleukin (IL)1β, IL2, IL4, IL5, IL6, IL8, IL10, IL12, IL13, sCD154, interferon-γ (IFNγ), soluble IL2 receptor (sIL2R), and tumor necrosis factor-α (TNFα), using the Luminex Multi-Analyte Profiling system. Differences in levels of cytokines between cases and controls were analyzed. Logistic regression was also performed.

Results

sCD154 was significantly elevated in cases compared to controls (p < 0.0001). IL1β, IL5, IL6, IL8, IL13, IFNγ, sIL2R, and TNFα were also significantly elevated in JIA. Levels of sCD154 were highly correlated with IL1β, IL6, IL8, and TNFα (p < 0.0001). Logistic regression analysis suggested that IL6 (odds ratio (OR): 1.4, p < 0.0001), sCD154 (OR: 1.1, p < 0.0001), and TNFα (OR: 1.1, p < 0.005) were positively associated with JIA, while IL10 (OR: 0.5, p < 0.002) was protective. sCD154 was elevated in all JIA subtypes, with highest levels among more severe subtypes. IL1β, IL6, IL8, sIL2R and TNFα were also elevated in several JIA subtypes.

Conclusion

Serum levels of sCD154, IL1β, IL6, IL8, sIL2R and TNFα are elevated in most JIA subtypes, suggesting a major role for sCD154, and these cytokines and cytokine receptors in the pathogenesis of JIA.