H-ferritin and pro-inflammatory cytokines are increased in the bone marrow of patients affected by macrophage activation syndrome

Abstract

Macrophage activation syndrome (MAS) is hyper-inflammatory life-threatening syndrome, typically associated with high levels of serum ferritin. This is an iron storage protein including heavy (H) subunits and light (L) subunits, categorised on their molecular weight. The H-/L-subunits ratio may be different in tissues, depending on the specific tissue and pathophysiologic status.

In this work, we analysed the bone marrow (BM) biopsies of adult MAS patients to assess the presence of: i. H-ferritin and L-ferritin; ii. CD68+/H-ferritin+ and CD68+/L-ferritin+; iii. IL-1β, TNF, IFN-γ. We also explored possible correlations of these results with clinical data.

H-ferritin, IL-1β, TNF and IFN-γ resulted to be significantly increased in MAS. Furthermore, an increased number of CD68+/H-ferritin+ cells and an infiltrate of cells co-expressing H-ferritin and IL-12, suggesting an infiltrate of M1 macrophages, were observed. H-ferritin levels and CD68+/H-ferritin+ cells resulted to be correlated with haematological involvement of the disease, serum ferritin and C-reactive protein. L-ferritin and CD68+/L-ferritin+ cells did not correlate with these parameters.

In conclusion, during MAS, H-ferritin, CD68+/H-ferritin+ cells and pro-inflammatory cytokines resulted to be significantly increased in the BM inflammatory infiltrate, pointing out a possible vicious pathogenic loop. To date, H-ferritin and CD68+/H-ferritin+ were significantly associated with haematological involvement of the disease, suggesting bio-markers assessing severity of clinical picture. This article is protected by copyright. All rights reserved.