The report with those findings, “The use of S100 proteins testing in juvenile idiopathic arthritis and autoinflammatory diseases in a pediatric clinical setting: a retrospective analysis,” was published in the journal Pediatric Rheumatology.
S100A8, S100A9, and S100A12 proteins have been proposed as sensitive biomarkers of inflammation and disease activity in patients with rheumatoid arthritis and JIA. S100A12 also has been linked to autoimmune diseases, where it is strongly produced in inflamed tissues from chronic arthritis patients.
This group of proteins plays an important role in setting up inflammatory responses in the body. They are highly produced and secreted by activated cells called neutrophils and macrophages, which contribute to the body’s first line of defense — known as the innate immune system.
In this study, researchers at Cincinnati Children’s Hospital Medical Center wanted to evaluate if testing for S100 proteins in the blood could aid doctors in making a diagnosis and determining disease activity in children with auto-inflammatory conditions, including JIA.
They studied 136 pediatric patients seen at the hospital’s rheumatology clinic, whose blood levels of S100A8/9 and S100A12 had been measured as part of their routine care.
Ninety-two patients had active disease — defined as one or more joints with symptoms — and 44 had inactive disease, defined as no symptomatic joints.
Among those with active disease, 21 had sJIA, 49 had non-systemic JIA, eight had other defined auto-inflammatory syndromes (AID), and 14 had systemic undifferentiated recurring fever syndromes (SURFS).
Within this group of patients (active disease), those with sJIA had the highest levels of S100A8/9 (31,465 ng/ml) and S100A12 (2075 ng/ml). Levels of C-reactive protein also were higher in the sJIA group.
By comparing patients with active and inactive disease, researchers saw that S100A8/9 and S100A12 values were not associated with disease activity in any group, except for patients with sJIA.
The three S100 proteins were significantly elevated in children with sJIA with active disease (22 patients) compared to those whose disease was inactive (12 patients).
Again, C-reactive protein levels followed a similar trend and were highest in children with active sJIA.
Regarding diagnostic utility, testing for S100 proteins slightly outperformed C-reactive protein tests for differentiating sJIA from other auto-inflammatory diseases or SURFS.
At a cut-off value of 5,630 ng/ml, S100A8/9 was 74% sensitive and 91% specific for separating patients with sJIA from those with other auto-inflammatory disorders. For S100A12, a cut-off of 363 ng/ml was 71% sensitive and 89% specific when doing the same distinction.
Notably, sensitivity refers to the ability to correctly identify children with sJIA, while specificity is the accurate identification of patients without this disorder.
“The S100 proteins are useful in distinguishing sJIA from other autoinflammatory and fever syndromes with high sensitivity and specificity. Levels of S100A8/9 and S100A12 are indicators of disease activity in sJIA but not in other autoinflammatory syndromes or nsJIA [non-systemic JIA],” the researchers wrote.
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