The Experts below are selected from a list of 3069 Experts worldwide ranked by ideXlab platform
Yehuda Shoenfeld - One of the best experts on this subject based on the ideXlab platform.
-
COVID-19 as part of the hyperferritinemic syndromes: the role of iron depletion therapy
Immunologic Research, 2020Co-Authors: Carlo Perricone, Yehuda Shoenfeld, Elena Bartoloni, Roberto Bursi, Giacomo Cafaro, Giacomo Maria Guidelli, Roberto GerliAbstract:SARS-CoV-2 infection is characterized by a protean clinical picture that can range from asymptomatic patients to life-threatening conditions. Severe COVID-19 patients often display a severe pulmonary involvement and develop neutrophilia, lymphopenia, and strikingly elevated levels of IL-6. There is an over-exuberant cytokine release with Hyperferritinemia leading to the idea that COVID-19 is part of the hyperferritinemic syndrome spectrum. Indeed, very high levels of ferritin can occur in other diseases including hemophagocytic lymphohistiocytosis, macrophage activation syndrome, adult-onset Still’s disease, catastrophic antiphospholipid syndrome and septic shock. Numerous studies have demonstrated the immunomodulatory effects of ferritin and its association with mortality and sustained inflammatory process. High levels of free iron are harmful in tissues, especially through the redox damage that can lead to fibrosis. Iron chelation represents a pillar in the treatment of iron overload. In addition, it was proven to have an anti-viral and anti-fibrotic activity. Herein, we analyse the pathogenic role of ferritin and iron during SARS-CoV-2 infection and propose iron depletion therapy as a novel therapeutic approach in the COVID-19 pandemic.
-
the hyperferritinemic syndrome macrophage activation syndrome still s disease septic shock and catastrophic antiphospholipid syndrome
BMC Medicine, 2013Co-Authors: Cristina Rosario, Gisele Zandmangoddard, Esther G Meyronholtz, David Dcruz, Yehuda ShoenfeldAbstract:Over the last few years, accumulating data have implicated a role for ferritin as a signaling molecule and direct mediator of the immune system. Hyperferritinemia is associated with a multitude of clinical conditions and with worse prognosis in critically ill patients. There are four uncommon medical conditions characterized by high levels of ferritin, namely the macrophage activation syndrome (MAS), adult onset Still’s disease (AOSD), catastrophic antiphospholipid syndrome (cAPS) and septic shock, that share a similar clinical and laboratory features, and also respond to similar treatments, suggesting a common pathogenic mechanism. Ferritin is known to be a pro-inflammatory mediator inducing expression of pro-inflammatory molecules, yet it has opposing actions as a pro-inflammatory and as an immunosuppressant. We propose that the exceptionally high ferritin levels observed in these uncommon clinical conditions are not just the product of the inflammation but rather may contribute to the development of a cytokine storm. Here we review and compare four clinical conditions and the role of ferritin as an immunomodulator. We would like to propose including these four conditions under a common syndrome entity termed “Hyperferritinemic Syndrome”.
-
Hyperferritinemia in autoimmunity.
The Israel Medical Association journal : IMAJ, 2008Co-Authors: Gisele Zandman-goddard, Yehuda ShoenfeldAbstract:Controlling iron/oxygen chemistry in biology depends on multiple genes, regulatory messenger RNA structures, signaling pathways and protein catalysts. Ferritin synthesis is regulated by cytokines (tumor necrosis factor-alpha and interleukin-1alpha) at various levels (transcriptional, post-transcriptional, translational) during development, cellular differentiation, proliferation and inflammation. The cellular response by cytokines to infection stimulates the expression of ferritin genes. The immunological actions of ferritin include binding to T lymphocytes, suppression of the delayed-type hypersensitivity, suppression of antibody production by B lymphocytes, and decreased phagocytosis of granulocytes. Thyroid hormone, insulin and insulin growth factor-1 are involved in the regulation of ferritin at the mRNA level. Ferritin and iron homeostasis are implicated in the pathogenesis of many disorders, including diseases involved in iron acquisition, transport and storage (primary hemochromatosis) as well as in atherosclerosis, Parkinson's disease, Alzheimer disease, and restless leg syndrome. Mutations in the ferritin gene cause the hereditary Hyperferritinemia-cataract syndrome and neuroferritinopathy. Hyperferritinemia is associated with inflammation, infections and malignancies, and in systemic lupus erythematosus correlates with disease activity. Some evidence points to the importance of Hyperferritinemia in dermatomyositis and multiple sclerosis, but further mechanistic investigations are warranted.
-
Ferritin in autoimmune diseases.
Autoimmunity Reviews, 2007Co-Authors: Gisele Zandman-goddard, Yehuda ShoenfeldAbstract:Iron, an essential element for many important cellular functions in all living organisms, can catalyze the formation of potentially toxic free radicals. Excessive iron is sequestered by ferritin in a nontoxic and readily available form in a cell. Ferritin is composed of 24 subunits of different proportions of two functionally distinct subunits: ferritin H and L. The expression of ferritin is under delicate control and is regulated at both the transcriptional and post-transcriptional levels by iron, cytokines, hormones, and oxidative stress. Mutations in the ferritin gene cause the hereditary Hyperferritinemia-cataract syndrome and neuroferritinopathy. Hyperferritinemia is associated with inflammation, infections, and malignancies. While elevated levels of ferritin are characteristic of adult-onset Still's disease and hemophagocytic syndrome, both associated with inflammation, it has scantly been evaluated in other autoimmune diseases. In this review, we describe ferritin structure and function, Hyperferritinemia in disease states and in autoimmune diseases.
Leslie Zypchen - One of the best experts on this subject based on the ideXlab platform.
-
Dysmetabolic Hyperferritinemia is associated with normal transferrin saturation, mild hepatic iron overload, and elevated hepcidin
Annals of Hematology, 2011Co-Authors: Luke Y.c. Chen, Silvia D. Chang, Gayatri M. Sreenivasan, Raewyn Broady, Peter W. Tsang, Leslie ZypchenAbstract:Hyperferritinemia is common in individuals with the metabolic syndrome (dysmetabolic Hyperferritinemia), but its pathophysiology and the degree to which it reflects tissue iron overload remains unclear. We conducted a cross-sectional study evaluating ten cases with dysmetabolic Hyperferritinemia for liver iron overload and compared their serum iron indices and urine hepcidin levels to healthy controls. Seven out of ten cases had mild hepatic iron overload by magnetic resonance imaging (MRI) (median, 75 μmol/g dry weight). Cases had higher serum ferritin than controls (median, 672 μg/L vs. 105 μg/L, p
-
Dysmetabolic Hyperferritinemia is associated with normal transferrin saturation, mild hepatic iron overload, and elevated hepcidin.
Annals of hematology, 2010Co-Authors: Luke Y.c. Chen, Peter Tsang, Silvia D. Chang, Gayatri M. Sreenivasan, Raewyn Broady, Leslie ZypchenAbstract:Hyperferritinemia is common in individuals with the metabolic syndrome (dysmetabolic Hyperferritinemia), but its pathophysiology and the degree to which it reflects tissue iron overload remains unclear. We conducted a cross-sectional study evaluating ten cases with dysmetabolic Hyperferritinemia for liver iron overload and compared their serum iron indices and urine hepcidin levels to healthy controls. Seven out of ten cases had mild hepatic iron overload by magnetic resonance imaging (MRI) (median, 75 μmol/g dry weight). Cases had higher serum ferritin than controls (median, 672 μg/L vs. 105 μg/L, p < 0.001), but the median transferrin saturation was not significantly different (38% vs. 36%, p = 0.5). Urinary hepcidin was elevated in dysmetabolic Hyperferritinemia (median; 1,584 ng/mg of creatinine vs. 799 ng/mg of creatinine, p = 0.05). Dysmetabolic Hyperferritinemia is characterized by Hyperferritinemia with normal transferrin saturation, elevated hepcidin levels, and mild liver iron overload in a subset of patients.
Agop Citak - One of the best experts on this subject based on the ideXlab platform.
-
Hyperferritinemia in the critically ill child with secondary hemophagocytic lymphohistiocytosis/sepsis/multiple organ dysfunction syndrome/macrophage activation syndrome: what is the treatment?
Critical care (London England), 2012Co-Authors: Demet Demirkol, Dincer Yildizdas, Benan Bayrakci, Bulent Karapinar, Tanil Kendirli, Tolga Koroglu, Oguz Dursun, Nilgun Erkek, Hakan Gedik, Agop CitakAbstract:Introduction Hyperferritinemia is associated with increased mortality in pediatric sepsis, multiple organ dysfunction syndrome (MODS), and critical illness. The International Histiocyte Society has recommended that children with Hyperferritinemia and secondary hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS) should be treated with the same immunosuppressant/cytotoxic therapies used to treat primary HLH. We hypothesized that patients with Hyperferritinemia associated secondary HLH/sepsis/MODS/MAS can be successfully treated with a less immunosuppressant approach than is recommended for primary HLH.
-
Hyperferritinemia in the critically ill child with secondary hemophagocytic lymphohistiocytosis sepsis multiple organ dysfunction syndrome macrophage activation syndrome what is the treatment
Critical Care, 2012Co-Authors: Demet Demirkol, Dincer Yildizdas, Benan Bayrakci, Bulent Karapinar, Tanil Kendirli, Tolga Koroglu, Oguz Dursun, Nilgun Erkek, Hakan Gedik, Agop CitakAbstract:Introduction Hyperferritinemia is associated with increased mortality in pediatric sepsis, multiple organ dysfunction syndrome (MODS), and critical illness. The International Histiocyte Society has recommended that children with Hyperferritinemia and secondary hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS) should be treated with the same immunosuppressant/cytotoxic therapies used to treat primary HLH. We hypothesized that patients with Hyperferritinemia associated secondary HLH/sepsis/MODS/MAS can be successfully treated with a less immunosuppressant approach than is recommended for primary HLH.
Luke Y.c. Chen - One of the best experts on this subject based on the ideXlab platform.
-
Dysmetabolic Hyperferritinemia is associated with normal transferrin saturation, mild hepatic iron overload, and elevated hepcidin
Annals of Hematology, 2011Co-Authors: Luke Y.c. Chen, Silvia D. Chang, Gayatri M. Sreenivasan, Raewyn Broady, Peter W. Tsang, Leslie ZypchenAbstract:Hyperferritinemia is common in individuals with the metabolic syndrome (dysmetabolic Hyperferritinemia), but its pathophysiology and the degree to which it reflects tissue iron overload remains unclear. We conducted a cross-sectional study evaluating ten cases with dysmetabolic Hyperferritinemia for liver iron overload and compared their serum iron indices and urine hepcidin levels to healthy controls. Seven out of ten cases had mild hepatic iron overload by magnetic resonance imaging (MRI) (median, 75 μmol/g dry weight). Cases had higher serum ferritin than controls (median, 672 μg/L vs. 105 μg/L, p
-
Dysmetabolic Hyperferritinemia is associated with normal transferrin saturation, mild hepatic iron overload, and elevated hepcidin.
Annals of hematology, 2010Co-Authors: Luke Y.c. Chen, Peter Tsang, Silvia D. Chang, Gayatri M. Sreenivasan, Raewyn Broady, Leslie ZypchenAbstract:Hyperferritinemia is common in individuals with the metabolic syndrome (dysmetabolic Hyperferritinemia), but its pathophysiology and the degree to which it reflects tissue iron overload remains unclear. We conducted a cross-sectional study evaluating ten cases with dysmetabolic Hyperferritinemia for liver iron overload and compared their serum iron indices and urine hepcidin levels to healthy controls. Seven out of ten cases had mild hepatic iron overload by magnetic resonance imaging (MRI) (median, 75 μmol/g dry weight). Cases had higher serum ferritin than controls (median, 672 μg/L vs. 105 μg/L, p < 0.001), but the median transferrin saturation was not significantly different (38% vs. 36%, p = 0.5). Urinary hepcidin was elevated in dysmetabolic Hyperferritinemia (median; 1,584 ng/mg of creatinine vs. 799 ng/mg of creatinine, p = 0.05). Dysmetabolic Hyperferritinemia is characterized by Hyperferritinemia with normal transferrin saturation, elevated hepcidin levels, and mild liver iron overload in a subset of patients.
Verena Schlaphoff - One of the best experts on this subject based on the ideXlab platform.
-
Hyperferritinemia and hypergammaglobulinemia predict the treatment response to standard therapy in autoimmune hepatitis.
PloS one, 2017Co-Authors: Richard Taubert, Matthias Hardtke-wolenski, Fatih Noyan, Claudine Lalanne, Danny Jonigk, Jerome Schlue, Till Krech, Ralf Lichtinghagen, Christine S. Falk, Verena SchlaphoffAbstract:Autoimmune hepatitis (AIH) is a chronic hepatitis with an increasing incidence. The majority of patients require life-long immunosuppression and incomplete treatment response is associated with a disease progression. An abnormal iron homeostasis or Hyperferritinemia is associated with worse outcome in other chronic liver diseases and after liver transplantation. We assessed the capacity of baseline parameters including the iron status to predict the treatment response upon standard therapy in 109 patients with untreated AIH type 1 (AIH-1) in a retrospective single center study. Thereby, a Hyperferritinemia (> 2.09 times upper limit of normal; Odds ratio (OR) = 8.82; 95% confidence interval (CI): 2.25–34.52) and lower immunoglobulins (
-
Hyperferritinemia and hypergammaglobulinemia predict the treatment response to standard therapy in autoimmune hepatitis
PLOS ONE, 2017Co-Authors: Richard Taubert, Fatih Noyan, Claudine Lalanne, Danny Jonigk, Jerome Schlue, Till Krech, Ralf Lichtinghagen, Christine S. Falk, Matthias Hardtkewolenski, Verena SchlaphoffAbstract:Autoimmune hepatitis (AIH) is a chronic hepatitis with an increasing incidence. The majority of patients require life-long immunosuppression and incomplete treatment response is associated with a disease progression. An abnormal iron homeostasis or Hyperferritinemia is associated with worse outcome in other chronic liver diseases and after liver transplantation. We assessed the capacity of baseline parameters including the iron status to predict the treatment response upon standard therapy in 109 patients with untreated AIH type 1 (AIH-1) in a retrospective single center study. Thereby, a Hyperferritinemia (> 2.09 times upper limit of normal; Odds ratio (OR) = 8.82; 95% confidence interval (CI): 2.25–34.52) and lower immunoglobulins (<1.89 times upper limit of normal; OR = 6.78; CI: 1.87–24.59) at baseline were independently associated with the achievement of complete biochemical remission upon standard therapy. The predictive value increased when both variables were combined to a single treatment response score, when the cohort was randomly split into a training (area under the curve (AUC) = 0.749; CI 0.635–0.863) and internal validation cohort (AUC = 0.741; CI 0.558–0.924). Patients with a low treatment response score (<1) had significantly higher cumulative remission rates in the training (p<0.001) and the validation cohort (p = 0.024). The baseline Hyperferritinemia was accompanied by a high serum iron, elevated transferrin saturations and mild hepatic iron depositions in the majority of patients. However, the abnormal iron status was quickly reversible under therapy. Mechanistically, the iron parameters were not stringently related to a hepatocellular damage. Ferritin rather seems deregulated from the master regulator hepcidin, which was down regulated, potentially mediated by the elevated hepatocyte growth factor. In conclusion, baseline levels of serum ferritin and immunoglobulins, which are part of the diagnostic work-up of AIH, can be used to predict the treatment response upon standard therapy in AIH-1, although confirmation from larger multicenter studies is pending.