Hepcidin: a promising marker for differential diagnosis of anemia and macrophage activation syndrome in children with juvenile idiopathic arthritis

Hepcidin is a 25-amino acid peptide, which is a key systemic regulator of iron metabolism. As considered, overproduction of hepcidin in the liver is controlled by high levels of proinflammatory cytokines. Is it known that interleukin-6 play a key role in the development of anemia in patients with juvenile idiopathic arthritis (JIA). However, IL-6 blockers itself may provoke the onset of Macrophage Activation Syndrome (MAS), manifesting, particularly, also with anemia. In view of the fact that macrophages involved in MAS express CD163 - a scavenger receptor that binds hemoglobin-haptoglobin complexes - and activate the pathways which are important for adaptation to oxidative stress induced by free iron, we can consider hepcidin as a welcome challenge to predict the development of MAS early in the course of the disease. During the study of 35 patients with JIA treated with biological disease-modifying drugs (tocilizumab and golimumab), direct relations between the level of hemoglobin and hepcidin were not found. However, it was found that the mean corpuscular hemoglobin level is associated with hepcidin concentration in patients with JIA. It was found that concentration of serum hepcidin may be used for early differential diagnosis of anemia and MAS in patients with JIA. High probability of evolution of anemia to MAS was found when concentration of hepcidin was 160 g/L. The following combinations were associated with high probability of evolution of slight anemia to a severe form, but not to MAS: 1. hepcidin >200 ng/mL and ferritin 140 ng/mL and soluble transferrin receptor 140 ng/mL and total iron binding capacity >46 mcmol/L. Misclassification should be assessed during further studies.