title: Increased level of H-ferritin and its imbalance with L-ferritin, in bone marrow and liver of patients with adult onset Still's disease, developing macrophage activation syndrome, correlate with the severity of the disease.
abstract: In this paper, we aimed to evaluate the levels of ferritin enriched in H subunits (H-ferritin) and ferritin enriched in L subunits (L-ferritin) and the cells expressing these 2 molecules, in the bone marrow (BM) and liver biopsies obtained from adult onset Still's disease (AOSD) patients who developed macrophage activation syndrome (MAS), and correlating these data with the severity of the disease. Twenty-one patients with MAS-associated AOSD underwent BM biopsy and among them, 9 patients with hepatomegaly and elevated liver enzymes underwent liver biopsy. All the samples were stained by both immunohistochemistry and immunofluorescence. A statistical analysis was performed to estimate the possible correlation among both H-ferritin and L-ferritin tissue expression and the clinical picture of the disease. Furthermore, the same analysis was performed to evaluate the possible correlation among the number of CD68/H-ferritin or CD68/L-ferritin positive cells and the clinical picture. Both immunohistochemical and immunofluorescence analysis demonstrated an increased tissue H-ferritin expression, in the BM and liver samples of our patients. This increased expression correlated with the severity of the disease. An inflammatory infiltrate, enriched in CD68 macrophages, expressing H-ferritin was observed in both the BM and the liver samples of our patients. Furthermore, we observed, that this increased number of CD68/H-ferritin positive cells significantly correlated with the severity of clinical picture and this specific BM infiltrate correlated with the mortality rate, reported in our cohort. Our data showed an imbalance between the levels of H- and L-ferritin in different organs of patients with MAS-associated AOSD and the evidence of a strong infiltrate of CD68/H-ferritin positive cells in the same organs. Furthermore, a strong correlation among both the tissue H-ferritin and the CD68/H-ferritin positive cells and the clinical picture was observed.
authors.affiliation: Division of Rheumatology, Department of Biotechnological and Applied Clinical Science, School of Medicine, University of L'Aquila, L'Aquila, Italy. Electronic address: pieroruscitti@live.com.
authors.forename: Piero
authors.initials: P
authors.lastname: Ruscitti
authors.affiliation: Division of Rheumatology, Department of Biotechnological and Applied Clinical Science, School of Medicine, University of L'Aquila, L'Aquila, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Cipriani
authors.affiliation: Division of Rheumatology, Department of Biotechnological and Applied Clinical Science, School of Medicine, University of L'Aquila, L'Aquila, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Di Benedetto
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, University of Palermo, Palermo, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Ciccia
authors.affiliation: Division of Rheumatology, Department of Biotechnological and Applied Clinical Science, School of Medicine, University of L'Aquila, L'Aquila, Italy.
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Liakouli
authors.affiliation: Division of Rheumatology, Department of Biotechnological and Applied Clinical Science, School of Medicine, University of L'Aquila, L'Aquila, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Carubbi
authors.affiliation: Division of Rheumatology, Department of Biotechnological and Applied Clinical Science, School of Medicine, University of L'Aquila, L'Aquila, Italy.
authors.forename: Onorina
authors.initials: O
authors.lastname: Berardicurti
authors.affiliation: Pathology, Ospedali Riuniti Villa Sofia-Cervello, Palermo, Italy.
authors.forename: Aroldo
authors.initials: A
authors.lastname: Rizzo
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, University of Palermo, Palermo, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Triolo
authors.affiliation: Division of Rheumatology, Department of Biotechnological and Applied Clinical Science, School of Medicine, University of L'Aquila, L'Aquila, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Giacomelli
mesh_terms: D000328:Adult; D017668:Age of Onset; D000818:Animals; D001052:Apoferritins / Q000032:analysis* / Q000378:metabolism; D001853:Bone Marrow / Q000737:chemistry*; D006801:Humans; D008099:Liver / Q000737:chemistry*; D055501:Macrophage Activation Syndrome / Q000378:metabolism*; D016706:Still's Disease, Adult-Onset / Q000378:metabolism*
chemical_list: D001052:Apoferritins
keywords: Adult-onset Still's disease; Hyperferritinemia; Macrophage activation syndrome