S100A12 as diagnostic tool in the differential diagnosis of sJIA associated MAS vs. hereditary or acquired HLH

Question Macrophage activation syndrome is a severe complication of autoimmune and autoinflammatory disease. MAS is most strongly associated with systemic juvenile idiopathic arthritis (sJIA) but can also be seen in Kawasaki disease, SLE or IBD. Clinically, MAS is strikingly similar to hemophagocytic lymphohistiocytosis (HLH) and the initial differentiation between sJIA-associated MAS and hereditary HLH or acquired HLH is very difficult. Due to recent advances in the description of HLH-related gene defects, most patients with hereditary HLH can be identified through genetic or functional analysis (intracellular perforin, SLAM-associated protein analysis, x-linked inhibitor of apoptosis, CD107 degranulation assay). Unfortunately these investigations are not always easily available. Since viral infections such as EBV and CMV can trigger both hereditary and acquired forms of HLH, the presence of a viral trigger in a patient with HLH does not necessarily allow classification of the disease as acquired HLH. S100A12 is an endogenous TLR4 ligand that induces monocyte activation, thereby acting as an amplifier of innate immunity during early inflammation. S100A12 is highly overexpressed in sJIA, and the assessment of S100A12 serum levels helps distinguish sJIA from other febrile illnesses. The main goal of this study was to determine whether S100A12 might help distinguish sJIA-associated MAS from HLH.