Inflammatory biomarkers in MAS
Inflammatory biomarkers may help identify MAS
Understanding which biomarkers to measure helps offer the best chance of optimizing patient outcomes.1
Some inflammatory biomarkers can be measured to evaluate key disease pathways, and their specificity may be helpful for identifying MAS.
These include:
Biomarker | Context |
CXCL9 | High serum levels of CXCL9, a chemokine selectively induced by IFNγ, can be observed with MAS onset and severity. Elevated CXCL9 levels may be helpful for differentiating MAS from an underlying rheumatic disease flare.2 |
CRP | CRP, ESR, and LDH are commonly available tests that may help assess the extent of hyperinflammation in patients with suspected MAS.3 Persistently high CRP levels and increasing D-dimers, in combination with a fall in ESR, and platelet count may suggest early stages of MAS development in febrile patients with underlying rheumatic disease. LDH is a general marker of cellular death or injury that is commonly elevated in patients with MAS.1,3,4 |
sCD25/sIL-2Rα | sCD25, also known as sIL-2Rα, is an inflammatory marker of T-cell activation that can be helpful for MAS diagnosis and as an indicator of treatment response.1,4 |
IL-18 | IL-18 testing can help measure inflammasome activation, which can lead to the development of MAS in certain contexts. Elevated IL-18 can be observed in patients with Still’s disease, but significant elevations above a patient’s baseline may suggest development of MAS.5,6 |
Neopterin | Neopterin and CD163 testing can indicate the activation and inflammatory status of macrophages, which are essential for MAS pathology.4,5,7 |
CRP=C-reactive protein; ESR=erythrocyte sedimentation rate; LDH=lactate dehydrogenase; sIL-2Rα=soluble interleukin 2 receptor alpha.
Some patients may experience recurrent MAS episodes. However, there is limited information about biomarkers or clinical factors that can predict this in patients.8

Monitoring trending lab values over time can provide important insights for diagnosing and managing MAS.7
References: 1. Shakoory B, Geerlinks A, Wilejto M, et al. The 2022 EULAR/ACR points to consider at the early stages of diagnosis and management of suspected haemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS). Arthritis Rheumatol. 2023;75(10):1714-1732. doi:10.1002/art.42636 2. Bracaglia C, de Graaf K, Pires Marafon D, et al. Elevated circulating levels of interferon-γ and interferon-γ-induced chemokines characterise patients with macrophage activation syndrome complicating systemic juvenile idiopathic arthritis. Ann Rheum Dis. 2017;76(1):166-172. doi:10.1136/annrheumdis-2015-209020 3. Minoia F, Davì S, Horne A, et al. Clinical features, treatment, and outcome of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis: a multinational, multicenter study of 362 patients. Arthritis Rheumatol. 2014;66(11):3160-3169. doi:10.1002/art.38802 4. Grom AA, Horne A, De Benedetti F. Macrophage activation syndrome in the era of biologic therapy. Nat Rev Rheumatol. 2016;12(5):259-268. doi:10.1038/nrrheum.2015.179 5. Schulert GS, Grom AA. Macrophage activation syndrome and cytokine-directed therapies. Best Pract Res Clin Rheumatol. 2014;28(2):277-292. doi:10.1016/j.berh.2014.03.002 6. Crayne C, Cron RQ. Pediatric macrophage activation syndrome, recognizing the tip of the iceberg. Eur J Rheumatol. 2020;7(Suppl1):S13-S20. doi:10.5152/eurjrheum.2019.19150 7. Lerkvaleekul B, Vilaiyuk S. Macrophage activation syndrome: early diagnosis is key. Open Access Rheumatol. 2018;10:117-128. doi:10.2147/OARRR.S151013 8. Erkens R, Esteban Y, Towe C, Schulert G, Vastert S. Pathogenesis and treatment of refractory disease courses in systemic juvenile idiopathic arthritis: refractory arthritis, recurrent macrophage activation syndrome and chronic lung disease. Rheum Dis Clin North Am. 2021;47(4):585-606. doi:10.1016/j.rdc.2021.06.003