Traditional laboratory parameters and IFNγ-related biomarkers in the diagnosis and management of MAS

To evaluate diagnostic and prognostic significance of traditional laboratory parameters of hyperinflammation and of the IFNγ-related biomarkers interleukin-18 (IL-18), CXCL9 and neopterin in macrophage activation syndrome (MAS) secondary to Still's disease (SD).

Forty-one patients with MAS and 24 patients with active pediatric SD from six Italian centers were enrolled. Samples were obtained at baseline (at initiation or within 48 hours of initiation of specific treatments) for MAS or active SD and at T1 (5-15 days from baseline) only from MAS. CXCL9, IL-18 and neopterin were measured by ELISA. The MAS clinical severity score (MCSS) was developed to define MAS severity (mild: score 0-4; severe: score 5-8).

In addition to the parameters included in the 2016 MAS criteria, lymphopenia and increased LDH reliably discriminated MAS from active SD. Levels of CXCL9, IL-18 and neopterin effectively discriminated MAS from active SD. Higher levels of the three IFNγ-related biomarkers at baseline were associated with a severe course MAS (MCSS>4). Combining levels at baseline of CXCL9 with those of ferritin, platelet count, fibrinogen and LDH, led to a prognostic score with sensitivity of 100 % and specificity of 74 % for severe MAS. Contingency analysis showed that CXCL9 >830 pg/ml and IL-18 >83,000 pg/ml at T1 had a significant risk of failing to achieve MAS remission in ≤2 months (odds ratio 9.3 and 5.4, respectively).

These findings highlight the potential role of CXCL9 measurement in supporting the diagnosis and guiding the therapeutic management of patients with MAS in clinical practice.