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* = Presenting author

P410 Anti-TNF improves iron availability in Inflammatory Bowel Diseases, modulating Pro-hepcidin in an Erythroferrone-independent fashion

F. Cavallaro*1, L. Pastorelli1, 2, L.F. Pisani1, L. Duca3, 4, R. Rigolini5, L. Spina1, G.E. Tontini1, N. Munizio1, E. Costa5, M.D. Cappellini3, 4, M. Vecchi1, 2

1IRCCS Policlinico San Donato, Gastroenterology and Gastrointestinal Endoscopy Unit, San Donato Milanese, Italy, 2University of Milan, Department of Biomedical Sciences for Health, Milan, Italy, 3University of Milan, Department of Clinical Sciences and Community, Milan, Italy, 4IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Department of Internal Medicine, Milan, Italy, 5IRCCS Policlinico San Donato, Operative Unit of Laboratory Medicine, San Donato Milanese, Italy

Background

Anaemia is a common feature of Inflammatory Bowel Disease (IBD), resulting from a combination of iron deficiency and of anaemia of chronic disease (ACD). ACD is characterized by macrophage iron retention induced by inflammatory conditions. Hepcidin, an acute phase protein, is the master inducer of iron accumulation during ACD. Hepcidin is potently induced by pro-inflammatory cytokines, such as IL-6 and inhibited by Erythroferrone, a newly discovered hormone, which is produced by erythroblasts in response to erythropoietin (EPO) stimulation (Kautz L, Nat Genet 2014; Kautz L, Blood 2014). Remarkably, TNF downregulates EPO, thus it reduces Erythroferrone production. Aim of the study was to evaluate whether anti-TNF therapy, while downregulating several pro-inflammatory mediators, modulates hepcidin and Erythroferrone production, leading to a restoration of normal iron homeostasis in IBD.

Methods

Sera were collected from 21 IBD patients undergoing Infliximab or Adalimumab therapy, before each anti-TNF administration, for the first 6 weeks of therapy. Pro-hepcidin, a dosable hepcidin precursor, EPO, Erythroferrone, C reactive protein (CRP), iron markers and haemoglobin levels were measured by means of immunoassays and clinical activity indexes evaluated.

Results

Serum pro-hepcidin was significantly decreased between baseline and week 6 (139.42 ± 18.96 vs. 94.14 ± 9.19 ng/ml, p=0.0048); consistently, circulating levels of other acute phase proteins, such as ferritin and CRP were reduced (68.19 ± 18.23 vs. 37.48 ± 13.22 ng/ml, p=0.0223 and 1.80 ± 0.42 vs. 0.53 ± 0.11 mg/dl, p=0.0036, respectively); we also detected an increase in serum iron (37.71 ± 2.77 vs. 45.14 ± 3.78 μg/dl, p=0.0501) and total transferrin (201.5 ± 8.12 vs. 241.2 ± 10.99 mg/dl, p=0.0048), which is consistent with the reduction of systemic inflammatory activation. Remarkably, at week 6, haemoglobin was significantly increased (11.44 ± 0.33 vs. 12.14 ± 0.29 g/dl, p=0.0137). No changes in EPO nor in Erythroferrone levels were detected.

Conclusion

Anti-TNF therapy improves iron metabolism and, subsequently, anaemia in IBD. This effect appears to be related to a relevant decrease of hepcidin, a master regulator of ACD. The downregulation of hepcidin production is likely to be induced by the modulation of the cytokine network, rather than to modifications of the newly identified EPO-Erythroferrone axis.