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Background <p>Juvenile Idiopathic Arthritis (JIA) includes a subset of oligoarticular patients who later extend to a polyarticular course (extended-to-be, ETB), resulting in worse outcomes. Predictors of extension remain poorly defined. We investigated whether interleukin-6 (IL-6) and fibroblast-like synoviocytes (FLS) contribute to this progression.</p> Methods <p>Synovial fluid samples from persistent oligoarticular patients who remained persistent (<i>≤</i> 4 joints involved) throughout their disease course and ETB patients were analyzed using protein antibody arrays and ELISA. Importantly, ETB samples were collected prior to clinical extension, and persistent samples were from patients who never extended during the course of their disease. FLS were isolated from synovial fluid and cultured to assess IL-6 secretion. Conditioned media experiments were performed to evaluate whether factors secreted by ETB FLS could influence IL-6 expression in persistent FLS.</p> Results <p>MANOVA revealed that (Wilks’ λ = 0.5446, F(9, 31) = 2.88, <i>p</i> = 0.0136) IL-6 and multiple IL-6–related cytokines were significantly elevated in synovial fluid from ETB patients compared to persistent patients. Quantitative ELISA confirmed higher IL-6 concentrations in ETB samples (1.46-fold increase, <i>p</i> = 0.047). FLS isolated from ETB patients prior to extension secreted significantly more IL-6 than persistent FLS (1.6-fold increase, <i>p</i> = 0.0239). Conditioned media from ETB FLS induced IL-6 production in persistent FLS to levels comparable to ETB FLS, demonstrating that soluble factors secreted early by ETB FLS can reprogram persistent FLS toward an inflammatory phenotype, even though these persistent FLS came from patients who remained clinically persistent throughout their disease course.</p> Conclusions <p>Our findings suggest factors secreted by ETB FLS including IL-6 protein may contribute to disease extension. These data highlight the potential role of early synovial signaling in shaping disease trajectory and support further investigation into IL-6 and FLS as possible therapeutic targets to prevent progression.</p>

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Soluble factors released from fibroblast-like synoviocytes of JIA patients with future extended course can condition persistent JIA synovial fibroblasts for increased IL-6 production

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月7日

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  • Megan M. Simonds,
  • Lina Al-Jaberi,
  • Hermine I. Brunner,
  • AnneMarie C. Brescia

摘要

Background

Juvenile Idiopathic Arthritis (JIA) includes a subset of oligoarticular patients who later extend to a polyarticular course (extended-to-be, ETB), resulting in worse outcomes. Predictors of extension remain poorly defined. We investigated whether interleukin-6 (IL-6) and fibroblast-like synoviocytes (FLS) contribute to this progression.

Methods

Synovial fluid samples from persistent oligoarticular patients who remained persistent (≤ 4 joints involved) throughout their disease course and ETB patients were analyzed using protein antibody arrays and ELISA. Importantly, ETB samples were collected prior to clinical extension, and persistent samples were from patients who never extended during the course of their disease. FLS were isolated from synovial fluid and cultured to assess IL-6 secretion. Conditioned media experiments were performed to evaluate whether factors secreted by ETB FLS could influence IL-6 expression in persistent FLS.

Results

MANOVA revealed that (Wilks’ λ = 0.5446, F(9, 31) = 2.88, p = 0.0136) IL-6 and multiple IL-6–related cytokines were significantly elevated in synovial fluid from ETB patients compared to persistent patients. Quantitative ELISA confirmed higher IL-6 concentrations in ETB samples (1.46-fold increase, p = 0.047). FLS isolated from ETB patients prior to extension secreted significantly more IL-6 than persistent FLS (1.6-fold increase, p = 0.0239). Conditioned media from ETB FLS induced IL-6 production in persistent FLS to levels comparable to ETB FLS, demonstrating that soluble factors secreted early by ETB FLS can reprogram persistent FLS toward an inflammatory phenotype, even though these persistent FLS came from patients who remained clinically persistent throughout their disease course.

Conclusions

Our findings suggest factors secreted by ETB FLS including IL-6 protein may contribute to disease extension. These data highlight the potential role of early synovial signaling in shaping disease trajectory and support further investigation into IL-6 and FLS as possible therapeutic targets to prevent progression.