High levels of interferon-gamma (IFNγ) in macrophage activation syndrome (MAS) and CXCL9 levels as a biomarker for IFNγ production in MAS

Serum levels of interleukin-18, CXCL9 and IFN-γ in Still’s disease complicated by macrophage activation syndrome

“…Self-perpetuating activation of T cells and macrophages with sustained production of pro-inflammatory cytokines including IL-18 and IFN-γ are key mediators of MAS [ 1 ]. IFN-γ has emerged as an important therapeutic target [ 3 ]. IFN-γ exerts its biologic activity predominantly in tissues, thus serum levels are overall a poor biomarker of disease activity [ 4 ].…”

“…IFN-γ exerts its biologic activity predominantly in tissues, thus serum levels are overall a poor biomarker of disease activity [ 4 ]. Serum CXCL9 level (downstream of IFN-γ) is a more promising surrogate biomarker for IFN-γ-driven systemic inflammation [ 3 ]. More recently, IL-18, an IFN-γ-inducing factor, is gaining attention, with higher levels reported in Still’s–MAS compared with pHLH, prompting some authors to suggest its potential to differentiate MAS from pHLH [ 5 ] or as a therapeutic target for MAS [ 6 , 7 ].…”

Case Report: Refractory macrophage activation syndrome requiring high-dose anakinra, emapalumab, and etoposide therapy in early-onset systemic juvenile idiopathic arthritis associated with adenoviremia

“…Emapalumab, an IFNγ-blocking monoclonal antibody, is effective in the treatment of pHLH, although its use in sHLH/MAS has yet to be approved and is under investigation (16)(17)(18). INFγ and IFNγrelated chemokines (CXCL9, CXCL10, CXLC11) levels are notably higher in patients with active sHLH/MAS and are tightly associated with laboratory markers of disease severity (18)(19)(20). These studies suggest that IFNγ is a potent driver of sHLH/MAS.…”

The novel use of emapalumab and ruxolitinib in acquired malignancy-associated hemophagocytic lymphohistiocytosis in pediatric patients

“…Her systemic inflammation worsened as evidenced by a rise in her ferritin, sIL-2 receptor, and CXCL9, a biomarker of IFNγ. [4] We held treatment for her lymphoma to reduce toxicities and better manage her HLH. With continued clinical deterioration, compassionate use of emapalumab, an IFNγ inhibitor indicated in primary HLH, led to dampening of her systemic inflammatory processes with resolution of fevers, decreased inflammatory markers, and signs of recovery of her hepatobiliary, renal, and gastrointestinal systems.…”