IL-18 Levels May Be Useful in Diagnosing, Predicting Disease Course in Juvenile Idiopathic Arthritis

Serum interleukin (IL)-18 levels greater than 4800 pg/mL may be useful in diagnosing systemic juvenile idiopathic arthritis (sJIA) and differentiating it from other diseases, according to study results published in Rheumatology (Oxford). Serum IL-18 levels may also be useful in predicting disease course and assessing remission in sJIA.

Researchers sought to explore the clinical significance of serum IL-18 levels for the diagnosis of sJIA and to predict its disease course.

A total of 116 patients with sJIA, 151 patients with other diseases, and 20 healthy, age-matched control participants were enrolled in the current study. Serum IL-18 levels were measured longitudinally in 41 patients with sJIA in the active phase, including disease onset and disease flare, through the inactive or remission phase. All serum IL-18 levels were quantified by the use of enzyme-linked immunosorbent assay (ELISA).

Criteria for sJIA in the active phase included active arthritis, rash, fever, generalized lymphadenopathy, splenomegaly, serositis, and elevated C-reactive protein (CRP) levels and/or erythrocyte sedimentation rate (ESR). Criteria for sJIA in the inactive phase included no arthritis, no rash, no fever, no generalized lymphadenopathy, no splenomegaly, no serositis, normal serum CRP levels and ESR, and Physician Global Assessment of disease activity that showed no disease activity.

Disease course of sJIA was defined as monocyclic course: no disease flare (n=20); chronic course: disease flare that occurred often after the withdrawal of steroids (n=11); and polycyclic pattern: disease flare that occurred repeatedly after achieving remission (n=10).

Serum IL-18 levels in patients with sJIA were significantly elevated compared with those in patients with Kawasaki disease (P <.0001), tumor necrosis factor receptor-associated periodic syndrome (P <.05), other subtypes of JIA (P <.0001), systemic lupus erythematosus (P <.01), juvenile dermatomyositis (P <.0001), leukemia (P <.05), and healthy control participants (P <.0001). On the other hand, serum levels in patients with sJIA were not significantly elevated compared with those in patients with familial Mediterranean fever.

Results of the study demonstrated that the serum IL-18 level cutoff value for the differentiation of sJIA from other diseases was 4800 pg/mL.

In patients with sJIA with a monocyclic disease course, serum IL-18 levels decreased steadily during the inactive phase, with low levels sustained during remission. However, in patients with a chronic disease course, elevated serum IL-18 levels were also sustained during the inactive phase. Further, among patients with a polycyclic disease course, serum IL-18 levels were elevated during flares of disease and then normalized during the inactive phase.

Serum IL-18 levels less than 595 pg/mL may be useful in the diagnosis of clinical remission in patients with sJIA.

One study limitation was the lack of inclusion of patients with sJIA who received IL-1 antagonists, such as anakinra and canakinumab.

However, the researchers concluded, “Monitoring of serum IL-18 levels might be useful for predicting the disease course and assessing remission in [sJIA].”

Reference

Mizuta M, Shimizu M, Inoue N, et al. Clinical significance of interleukin-18 for the diagnosis and prediction of disease course in systemic juvenile idiopathic arthritis. Rheumatology (Oxford). Published online November 17, 2020. doi:10.1093/rheumatology/ keaa634