32 results on '"Hyperferritinemia"'
Search Results
2. Lysinuric protein intolerance caused by a homozygous SLC7A7 deletion and presented with hyperferritinemia and osteoporosis in two siblings
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Irem Kalay, Hüseyin Aykut, Zuhal Caliskan, Gökhan Yigit, and Bernd Wollnik
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Lysinuric protein intolerance (LPI) ,SLC7A7 deletion ,Hyperferritinemia ,Multiple bone fractures ,Medicine (General) ,R5-920 ,Biology (General) ,QH301-705.5 - Abstract
Lysinuric protein intolerance (LPI) is a rare, inherited aminoaciduria caused by biallelic pathogenic variants in the amino acid transporter gene SLC7A7 (OMIM *603593). Individuals with LPI show extreme variability in their clinical presentation, and LPI is included in the differential diagnosis of several disorders such as urea cycle disorders, lysosomal storage diseases, malabsorption diseases, autoimmune disorders, hemochromatosis, and osteoporosis. The phenotypic variability of LPI and the lack of a specific clinical presentation have caused various misdiagnoses. Here, we report two siblings diagnosed in their 4th decade of life with LPI, manifesting rare hyperferritinemia. Additionally, they presented with short stature, multiple bone fractures due to osteoporosis, and they showed an aversion to protein-rich food. Using a combination of exome sequencing, microarray analysis and qPCR, we identified a novel homozygous deletion in SLC7A7 encompassing exons 3 to 10, which is predicted to lead to disruption of SLC7A7 function. This is the first report of lysinuric protein intolerance in a Turkish family associated with this so far unknown deletion in SLC7A7.
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- 2023
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3. Therapeutic potential of induced iron depletion using iron chelators in Covid-19
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Punnoth Poonkuzhi Naseef, Muhammed Elayadeth-Meethal, K.T. Mohammed Salim, A Anjana, C Muhas, K. Abdul Vajid, and Mohamed Saheer Kuruniyan
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COVID 19 ,Hyperferritinemia ,Pathogenesis ,Genomics ,Proteomic interaction ,Iron Chelator ,Biology (General) ,QH301-705.5 - Abstract
Ferritin, which includes twenty-four light and heavy chains in varying proportions in different tissues, is primarily responsible for maintaining the body's iron metabolism. Its normal value is between 10 and 200 ngmL−1 in men and between 30 and 300 ngmL−1 in women. Iron is delivered to the tissue via them, and they act as immunomodulators, signaling molecules, and inflammatory markers. When ferritin level exceeds 1000 µgL-1, the patient is categorized as having hyperferritinemia. Iron chelators such as deferiprone, deferirox, and deferoxamine are currently FDA approved to treat iron overload. The inflammation cascade and poor prognosis of COVID-19 may be attributed to high ferritin levels. Critically ill patients can benefit from deferasirox, an iron chelator administered orally at 20–40 mgkg−1 once daily, as well as intravenous deferoxamine at 1000 mg initially followed by 500 mg every 4 to 12 h. It can be combined with monoclonal antibodies, antioxidants, corticosteroids, and lactoferrin to make iron chelation therapy effective for COVID-19 victims. In this article, we analyze the antiviral and antifibrotic activity of iron chelators, thereby promoting iron depletion therapy as a potentially innovative treatment strategy for COVID-19.
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- 2022
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4. Epstein-Barr virus induced acute hepatitis with hyperferritinemia: A rare presentation
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Bassam Theodory, Meena Dopp, Austin R. Swisher, Roberto M. Flores, and Paul M. Robb
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Acute cholestatic hepatitis ,Epstein-Barr virus ,Hyperferritinemia ,Case report ,Infectious and parasitic diseases ,RC109-216 - Abstract
Elevated aminotransaminases and hyperbilirubinemia are common in primary Epstein-Barr Virus (EBV) infection in the adult and pediatric population and the disease course is usually subclinical and self-limited. However, EBV-induced hepatitis is an uncommon diagnosis, accounting for less than 1% of acute hepatitis causes. Acute EBV-hepatitis usually affects immunocompromised and older populations, with nearly half of patients being aged greater than 60 years. Significantly elevated ferritin levels correlate with severe infection and have been associated with EBV complications such as infectious mononucleosis, autoimmune hemolytic anemia, and hemophagocytic lymphohistiocytosis. We present a case of isolated acute cholestatic EBV-hepatitis and hyperferritinemia in an adult immunocompetent patient.
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- 2023
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5. Low transferrin levels predict heightened inflammation in patients with COVID-19: New insights
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Catherine Claise, Jumana Saleh, Marwa Rezek, Sophie Vaulont, Carole Peyssonnaux, and Marvin Edeas
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Transferrin ,Cytokine storm ,IL-6 ,Serum iron ,Hyperferritinemia ,Transferrin saturation ,Infectious and parasitic diseases ,RC109-216 - Abstract
Objectives: Mounting evidence links hyperinflammation in gravely ill patients to low serum iron levels and hyperferritinemia. However, little attention has been paid to other iron-associated markers such as transferrin. The aim of this study was to investigate the association of different iron parameters in severe COVID-19 and their relation to disease severity. Subjects and methods: This study involved 73 hospitalized patients with positive test results for SARS-CoV-2. Patients were classified into two groups according to symptom severity: mild and severe. Blood levels of anti–SARS-CoV-2 antibodies, interleukin 6 (IL-6), C-reactive protein (CRP), and iron-related biomarkers were measured. Results: The results revealed a significant increase in IL-6, CRP, and ferritin levels and decreased transferrin and iron levels in severe COVID-19. Transferrin negatively predicted variations in IgM and IgG levels (P < 0.001), as well as 34.4% and 36.6% increase in IL-6 and CRP levels, respectively (P < 0.005). Importantly, transferrin was the main negative predictor of ferritin levels, determining 22.7% of serum variations (P < 0.001). Conclusion: Reduced serum transferrin and iron levels, along with the increased CRP and high ferritin, were strongly associated with the heightened inflammatory and immune state in COVID-19. Transferrin can be used as a valuable predictor of increased severity and progression of the disease.
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- 2022
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6. Non-invasive methods for iron overload evaluation in dysmetabolic patients
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Paula Pessin Fábrega Branisso, Claudia Pinto Marques Souza de Oliveira, Hilton Muniz Leão Filho, Fabiana Roberto Lima, Aritânia Sousa Santos, Marcio Correa Mancini, Maria Edna de Melo, Flair José Carrilho, Manoel de Souza Rocha, Paul Clark, Henrique José Pereira Branisso, and Cintia Cercato
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Hyperferritinemia ,Non-alcoholic fatty liver disease ,Relaxometry ,Dysmetabolic iron overload syndrome ,Specialties of internal medicine ,RC581-951 - Abstract
Introduction: Although hyperferritinemia may reflect the inflammatory status of patients with non-alcoholic fatty liver disease (NAFLD), approximately 33% of hyperferritinemia cases reflect real hepatic iron overload. Aim: To evaluate a non-invasive method for assessing mild iron overload in patients with NAFLD using 3T magnetic resonance imaging (MRI) relaxometry, serum hepcidin, and the expression of ferritin subunits. Methods: This cross-sectional study assessed patients with biopsy-proven NAFLD. MRI relaxometry was performed using a 3T scanner in all patients, and the results were compared with iron content determined by liver biopsy. Ferritin, hepcidin, and ferritin subunits were assessed and classified according to ferritin levels and to siderosis identified by liver biopsy. Results: A total of 67 patients with NAFLD were included in the study. MRI revealed mild iron overload in all patients (sensitivity, 73.5%; specificity, 70%). For mild (grade 1) siderosis, the transverse relaxation rate (R2*) threshold was 58.9 s−1 and the mean value was 72.5 s−1 (SD, 33.9), while for grades 2/3 it was 88.2 s−1 (SD, 31.9) (p 30.2 ng/mL (sensitivity, 87%; specificity, 82%). Ferritin H and ferritin L subunits were expressed similarly in patients with NAFLD, regardless of siderosis. There were no significant differences in laboratory test results between the groups, including glucose parameters and liver function tests. Conclusions: MRI relaxometry and serum hepcidin accurately assessed mild iron overload in patients with dysmetabolic iron overload syndrome.
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- 2022
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7. Very unusual extremely high ferritin with cytokine release syndrome in a patient with hematological malignancy after experimental chimeric antigen receptor (CAR)-T-Cell therapy.
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Hoyt R, Ye Z, and Dasgupta A
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- Humans, Male, Middle Aged, Hematologic Neoplasms therapy, Lymphohistiocytosis, Hemophagocytic therapy, Lymphohistiocytosis, Hemophagocytic immunology, Cytokine Release Syndrome etiology, Cytokine Release Syndrome therapy, Ferritins, Immunotherapy, Adoptive adverse effects, Receptors, Chimeric Antigen immunology
- Abstract
Background: Chimeric antigen receptor (CAR) T cell therapy is an immunotherapy that has resulted in tremendous progress in the treatment of patients with B cell malignancies. However, significant toxicities may also be associated with such therapy. Here we report extremely high ferritin in a male patient after such therapy., Case Presentation: We present a case of a 52 year old male with a history of B-cell acute lymphoblastic leukemia who received chimeric antigen receptor T-cell (CAR-T) therapy with rapcabtagene autoleucel (carvykti). The patient subsequently developed cytokine release syndrome (CRS) which during its resolution results in a hemophagocytic lymphohistiocytosis (HLH)-like syndrome that fell short of being diagnostic. This syndrome tracked closely with the onset and resolution of immune-effector cell-associated neurotoxicity syndrome (ICANS), with close correlation between the severity of laboratory abnormalities, particularly extremely high ferritin (peak value: 81,540 μg/L), and clinical encephalopathy., Conclusions: Cytokine release syndrome after experimental (CAR) T cell therapy may cause extremely elevated ferritin and hemophagocytic lymphohistiocytosis -like syndrome., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
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- 2024
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8. Acute symmetric peripheral gangrene following a long-standing Mycobacterium malmoense infection: A very rare kinship
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Frans Maruma, MBChB, DipHivMed, AAAM, MMed-Derm, FC Derm(SA), Richard Carter, MBChB, MMed-Int Med, FCP (SA), Fatima Moosa, MBChB, Harriet Makuru, MBChB, and Taahir Asmal, BOptom, MBChB
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arteritis ,disseminated intravascular coagulation ,hyperferritinemia ,Mycobacterium malmoense ,symmetric peripheral gangrene ,Dermatology ,RL1-803 - Published
- 2020
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9. The role of iron in the pathogenesis of COVID-19 and possible treatment with lactoferrin and other iron chelators
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Hosam M. Habib, Sahar Ibrahim, Aamnah Zaim, and Wissam H. Ibrahim
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COVID-19 ,Hemoglobin damage ,Iron overload ,Free iron ,Hypercoagulation ,Hyperferritinemia ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Iron overload is increasingly implicated as a contributor to the pathogenesis of COVID-19. Indeed, several of the manifestations of COVID-19, such as inflammation, hypercoagulation, hyperferritinemia, and immune dysfunction are also reminiscent of iron overload. Although iron is essential for all living cells, free unbound iron, resulting from iron dysregulation and overload, is very reactive and potentially toxic due to its role in the generation of reactive oxygen species (ROS). ROS react with and damage cellular lipids, nucleic acids, and proteins, with consequent activation of either acute or chronic inflammatory processes implicated in multiple clinical conditions. Moreover, iron-catalyzed lipid damage exerts a direct causative effect on the newly discovered nonapoptotic cell death known as ferroptosis. Unlike apoptosis, ferroptosis is immunogenic and not only leads to amplified cell death but also promotes a series of reactions associated with inflammation. Iron chelators are generally safe and are proven to protect patients in clinical conditions characterized by iron overload. There is also an abundance of evidence that iron chelators possess antiviral activities. Furthermore, the naturally occurring iron chelator lactoferrin (Lf) exerts immunomodulatory as well as anti-inflammatory effects and can bind to several receptors used by coronaviruses thereby blocking their entry into host cells. Iron chelators may consequently be of high therapeutic value during the present COVID-19 pandemic.
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- 2021
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10. Impact of H63D mutations, magnetic resonance and metabolic syndrome among outpatient referrals for elevated serum ferritin in the Basque Country
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Agustin Castiella, Eva Zapata, Leire Zubiaurre, Jose Ma. Alustiza, Ma. Dolores De Juan, Arantxa Iribarren, Jose I. Emparanza, and Pedro Otazua
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Hyperferritinemia ,HFE gene ,Hemochromatosis ,MRI ,Metabolic syndrome ,Specialties of internal medicine ,RC581-951 - Abstract
Background and Aims. There are limited data on clinical and phenotypic characteristics of outpatients referred for hyperferritinemia (HF). To determine the causes of HF in outpatients referred to a secondary hospital.Material and methods. A prospective study of 132 consecutive patients with HF (> 200 μg/L, women; > 300 μg/L, men) was conducted from January-December 2010.Results. Mean age, 54.42 years (SD: 13.47, range: 23-83); body mass index (BMI), 28.80 (SD: 3.96, 17-39); ferritin (SF), 579.54 ng/mL (SD: 296.575, 206-1668); transferrin saturation (TSI), 43.87% (SD: 14.09, 12-95); iron (Fe), 134 μg/dL (SD: 49.68, 55-322); overweight: 48.31%, and obese: 40.44% (89%), and most patients were men (108/132). Regarding HFE mutations, H63D/H63D genotype and H63D allele frequencies were 17.5% (vs. 7.76% in controls); and 36% (31% in controls) respectively. While 63.6% consumed no alcohol, 18.1% consumed ≥ 60 g/day, the mean being 20.83 (SD: 33.95, 0-140). Overall, 6/132 (4.5%) patients were positive for B or C hepatitis. Mean LIC by MRI was 36.04 (SD: 32.78, 5-210), 53 patients having normal concentrations (< 36 µmol/g), 22 (33%) iron overload (37-80), and 4 (5%) high iron overload (> 80). Metabolic syndrome (MS) was detected in 44/80 men (55%) and 10/17 women (59%). In this group, the genotype frequency of the H63D/H63D mutation was significantly higher than in controls-21.56% vs. 7.76%- (p = 0.011); the H63D allelic frequency was 42.15% in MS group and 31% in controls (p = 0.027).Conclusion. The H63D/H63D genotype and H63D allele predispose individuals to HF and MS. MRI revealed iron overload in 33% of patients.
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- 2015
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11. Serum ferritin is a biomarker for liver mortality in the Hemochromatosis and Iron Overload Screening Study
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Paul C. Adams, James C. Barton, Helen Guo, David Alter, and Mark Speechley
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Survival analysis ,Population screening ,Hyperferritinemia ,Specialties of internal medicine ,RC581-951 - Abstract
Background. We identified no reports of long-term follow-up of participants in hemochromatosis screening programs. We evaluated causes of death and survival in non-C282Y homozygous Canadian participants in the primary care-based hemochromatosis and iron overload screening (HEIRS) study.Material and methods. Initial screening (IS) included transferrin saturation (TS), serum ferritin (SF), HFE genotyping (C282Y, H63D), and health questionnaire responses. By definition, participants without C282Y or H63D had HFE wt/wt. We linked 20,306 Canadian participants to the Ontario Death Registry for dates and causes of death 9 y after IS. We computed Cox proportional hazards to identify factors with increased death risks and Kaplan-Meier curves to estimate survival of non-C282Y homozygous participants with SF ≤ 1,000 µg/L and > 1,000 µg/dL.Results. There were 19,052 evaluable participants (IS mean age 49 y; 60% women; 93 C282Y homozygotes). There were 988 deaths. Significantly increased hazard ratios for all-cause mortality were positively associated with TS, SF, men, and C282Y homozygosity, and liver disease, diabetes, and heart failure reports. Non-C282Y homozygous participants with SF > 1,000 µg/L had lower survival than those with SF ≤ 1,000 µg/L (p < 0.0001).Conclusions. Nine years after initial screening, non-C282Y homozygous participants and SF > 1,000 µg/L was associated with decreased survival.
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- 2015
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12. Narrative Review of Hyperferritinemia, Iron Deficiency, and the Challenges of Managing Anemia in Aboriginal and Torres Strait Islander Australians With CKD
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Alan Cass, Geetha Rathnayake, Jaquelyne T. Hughes, Federica Barzi, Sandawana William Majoni, and Paul D. Lawton
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medicine.medical_specialty ,Indigenous Australians ,Anemia ,medicine.medical_treatment ,030232 urology & nephrology ,Prevalence ,Context (language use) ,Review ,030204 cardiovascular system & hematology ,lcsh:RC870-923 ,urologic and male genital diseases ,Aboriginal and Torres Strait Islander Australians ,03 medical and health sciences ,ESKD and dialysis ,0302 clinical medicine ,iron deficiency ,hyperferritinemia ,medicine ,Renal replacement therapy ,Intensive care medicine ,biology ,business.industry ,Transferrin saturation ,ferritin ,Iron deficiency ,medicine.disease ,lcsh:Diseases of the genitourinary system. Urology ,anemia ,female genital diseases and pregnancy complications ,Ferritin ,Nephrology ,biology.protein ,business ,chronic kidney disease ,Kidney disease - Abstract
Aboriginal and Torres Strait Islander Australians (Indigenous Australians) suffer some of the highest rates of chronic kidney disease (CKD) in the world. Among Indigenous Australians in remote areas of the Northern Territory, prevalence rates for renal replacement therapy (RRT) are up to 30 times higher than national prevalence. Anemia among patients with CKD is a common complication. Iron deficiency is one of the major causes. Iron deficiency is also one of the key causes of poor response to the mainstay of anemia therapy with erythropoiesis-stimulating agents (ESAs). Therefore, the effective management of anemia in people with CKD is largely dependent on effective identification and correction of iron deficiency. The current identification of iron deficiency in routine clinical practice is dependent on 2 surrogate markers of iron status: serum ferritin concentration and transferrin saturation (TSAT). However, questions exist regarding the use of serum ferritin concentration in people with CKD because it is an acute-phase reactant that can be raised in the context of acute and chronic inflammation. Serum ferritin concentration among Indigenous Australians receiving RRT is often markedly elevated and falls outside reference ranges within most national and international guidelines for iron therapy for people with CKD. This review explores published data on the challenges of managing anemia in Indigenous people with CKD and the need for future research on the efficacy and safety of treatment of anemia of CKD in patients with high ferritin and evidence iron deficiency.
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- 2020
13. Porphyria cutanea tarda in an HCV-positive liver transplant patient: a case report
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Adriano M. Pellicelli, M.D., Aldo Morrone, Luca Barbieri, and Arnaldo Andreoli
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Ribavirin ,Hemolysis ,Hyperferritinemia ,Pegylated interferon ,Specialties of internal medicine ,RC581-951 - Abstract
Introduction. Porphyria cutanea tarda (PCT) is the most common type of porphyria. The strong association between PCT and hepatitis C virus (HCV) infection is well established. Although antiviral treatment of chronic hepatitis C may improve PCT in some cases, de novo onset of PCT has been observed in patients undergoing peginterferon/ribavirin treatment. We present a rare case of a genotype 3 HCV-positive liver transplant recipient who developed PCT during antiviral treatment and discuss its probable etiopathogenesis.Case presentation. A genotype 3 HCV-positive liver transplant recipient, a 42-year-old man, was treated with peginterferon alfa-2a (180 μg/week) combined with ribavirin (1,200 mg/day) for recurrence of HCV infection after liver transplantation. He presented with hyperferritinemia but tested negative for genetic hemochromatosis (C282Y and H63D mutations). During antiviral therapy, he developed skin lesions on his hands characterized by vesicles and erosions consistent with PCT. PCT was confirmed by skin biopsy and elevated urinary uroporphyrin levels (1,469 mg/24 h). He was treated with chloroquine (200 mg) twice weekly, resulting in gradual regression of the skin lesions. Antiviral treatment was stopped after 48 weeks, and the patient achieved a sustained virological response. In conclusion, we report an extremely rare case of PCT in a genotype 3 HCV-positive liver transplant patient treated with antiviral therapy. We believe that the combination of HCV genotype 3 infection; hemolysis due to ribavirin treatment; and increased plasma levels of cytokines, such as IL-6 and TNFα, could have altered the patient's iron metabolism and thus caused PCT.
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- 2012
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14. Ferritin overexpression in Drosophila glia leads to iron deposition in the optic lobes and late-onset behavioral defects
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Stylianos Kosmidis, Jose A. Botella, Konstantinos Mandilaras, Stephan Schneuwly, Efthimios M.C. Skoulakis, Tracey A. Rouault, and Fanis Missirlis
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Optic lamina ,Inclusions ,Metals ,Circadian clock ,Restless legs ,Hyperferritinemia ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Cellular and organismal iron storage depends on the function of the ferritin protein complex in insects and mammals alike. In the central nervous system of insects, the distribution and relevance of ferritin remain unclear, though ferritin has been implicated in Drosophila models of Alzheimers' and Parkinsons' disease and in Aluminum-induced neurodegeneration. Here we show that transgene-derived expression of ferritin subunits in glial cells of Drosophila melanogaster causes a late-onset behavioral decline, characterized by loss of circadian rhythms in constant darkness and impairment of elicited locomotor responses. Anatomical analysis of the affected brains revealed crystalline inclusions of iron-loaded ferritin in a subpopulation of glial cells but not significant neurodegeneration. Although transgene-induced glial ferritin expression was well tolerated throughout development and in young flies, it turned disadvantageous at older age. The flies we characterize in this report contribute to the study of ferritin in the Drosophila brain and can be used to assess the contribution of glial iron metabolism in neurodegenerative models of disease.
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- 2011
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15. SARS-CoV-2-induced hypomethylation of the ferritin heavy chain (FTH1) gene underlies serum hyperferritinemia in severe COVID-19 patients.
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Muhammad JS, ElGhazali G, Shafarin J, Mohammad MG, Abu-Qiyas A, and Hamad M
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- Apoferritins genetics, DNA Methylation, Ferritins metabolism, Hepcidins genetics, Hepcidins metabolism, Humans, Iron metabolism, Oxidoreductases metabolism, Receptors, Transferrin, SARS-CoV-2, COVID-19 genetics, Hyperferritinemia
- Abstract
High serum ferritin (hyperferritinemia), a reliable hallmark of severe COVID-19 often associates with a moderate decrease in serum iron (hypoferremia) and a moderate increase in serum hepcidin. This suggests that hyperferritinemia in severe COVID-19 is reflective of inflammation rather than iron overload. To test this possibility, the expression status of ferritin heavy chain (FTH1), transferrin receptor 1 (TFRC), hepcidin (HAMP), and ferroportin (SLC40A1) genes and promoter methylation status of FTH1 and TFRC genes were examined in blood samples obtained from COVID-19 patients showing no, mild or severe symptoms and in healthy-donor monocytes stimulated with SARS-CoV-2-derived peptides. Severe COVID-19 samples showed a significant increase in FTH1 expression and hypomethylation relative to mild or asymptomatic COVID-19 samples. S-peptide treated monocytes also showed a significant increase in FTH1 expression and hypomethylation relative to that in controls; treatment with ECD or NP did not change FTH1 expression nor its methylation status. In silico and in vitro analysis showed a significant increase in the expression of the TET3 demethylase in S peptide-treated monocytes. Findings presented here suggest that S peptide-driven hypomethylation of the FTH1 gene promoter underlies hyperferritinemia in severe COVID-19 disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)
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- 2022
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16. Infliximab treatment for refractory COVID-19-associated multisystem inflammatory syndrome in a Japanese child.
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Yamaguchi Y, Takasawa K, Irabu H, Hiratoko K, Ichigi Y, Hirata K, Tamura Y, Murakoshi M, Yamashita M, Nakatani H, Shimoda M, Ishii T, Udagawa T, Shimizu M, Kanegane H, and Morio T
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- Humans, Immunoglobulins, Intravenous therapeutic use, Infliximab therapeutic use, Japan, Male, SARS-CoV-2, Systemic Inflammatory Response Syndrome drug therapy, COVID-19 complications, Connective Tissue Diseases, Hyperferritinemia, Mucocutaneous Lymph Node Syndrome complications, Mucocutaneous Lymph Node Syndrome diagnosis, Mucocutaneous Lymph Node Syndrome drug therapy, COVID-19 Drug Treatment
- Abstract
Patients with multisystem inflammatory syndrome in children (MIS-C) can develop clinical features resembling Kawasaki disease (KD). A full picture of MIS-C in East Asia which has higher incidence of KD than other regions remains unclear. We report on a 15-year-old Japanese boy with refractory MIS-C who was successfully treated with infliximab. A Japanese boy who was diagnosed with coronavirus disease 2019 (COVID-19) before a month developed MIS-C with fulfilling six principal symptoms of KD. Laboratory data showed extreme hyperferritinemia (11,404 ng/mL), besides lymphopenia and thrombocytopenia. The patient was refractory to initial therapy with intravenous immunoglobulin (IVIG; 2 g/kg), aspirin, and prednisolone. He was therefore administered a second IVIG (2 g/kg) and infliximab (5 mg/kg) on days 7 and 8 from the onset of fever, respectively, which resulted in an improvement of clinical symptoms. Only four Japanese cases with MIS-C were reported and all of them were responsive to IVIG. The hyperferritinemia in this case was distinctive from previously reported MIS-C cases in Japan and other cohorts and may be associated with refractoriness to IVIG therapy. Marked elevation of circulating ferritin levels is known to be induced by tumor necrosis factor-α, which plays a key role in the pathogenesis of both KD and MIS-C. Thus, for MIS-C patients with hyperferritinemia, early intervention with adjunctive infliximab may induce a more rapid resolution of inflammation and improve outcome. Because MIS-C may be heterogeneous with respect to immunopathology, genetic background, clinical phenotypes and response to therapies, optimized treatment strategies according to immunopathogenesis are required., (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)
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- 2022
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17. Low transferrin levels predict heightened inflammation in patients with COVID-19: New insights.
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Claise C, Saleh J, Rezek M, Vaulont S, Peyssonnaux C, and Edeas M
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- Biomarkers, C-Reactive Protein metabolism, Humans, Inflammation, SARS-CoV-2, COVID-19 diagnosis, Transferrin analysis, Transferrin metabolism
- Abstract
Objectives: Mounting evidence links hyperinflammation in gravely ill patients to low serum iron levels and hyperferritinemia. However, little attention has been paid to other iron-associated markers such as transferrin. The aim of this study was to investigate the association of different iron parameters in severe COVID-19 and their relation to disease severity., Subjects and Methods: This study involved 73 hospitalized patients with positive test results for SARS-CoV-2. Patients were classified into two groups according to symptom severity: mild and severe. Blood levels of anti-SARS-CoV-2 antibodies, interleukin 6 (IL-6), C-reactive protein (CRP), and iron-related biomarkers were measured., Results: The results revealed a significant increase in IL-6, CRP, and ferritin levels and decreased transferrin and iron levels in severe COVID-19. Transferrin negatively predicted variations in IgM and IgG levels (P < 0.001), as well as 34.4% and 36.6% increase in IL-6 and CRP levels, respectively (P < 0.005). Importantly, transferrin was the main negative predictor of ferritin levels, determining 22.7% of serum variations (P < 0.001)., Conclusion: Reduced serum transferrin and iron levels, along with the increased CRP and high ferritin, were strongly associated with the heightened inflammatory and immune state in COVID-19. Transferrin can be used as a valuable predictor of increased severity and progression of the disease., Competing Interests: Conflict of interest The authors declare no conflict of interest., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2022
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18. Reply to: "Ceruloplasmin variants might have different effects in different iron overload disorders".
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Corradini E and Valenti LV
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- Ceruloplasmin genetics, Humans, Hemochromatosis genetics, Iron Overload genetics
- Abstract
Competing Interests: Conflict of interest The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details.
- Published
- 2021
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19. Impact of H63D mutations, magnetic resonance and metabolic syndrome among outpatient referrals for elevated serum ferritin in the Basque Country
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Jose I. Emparanza, Arantxa Iribarren, José Mª Alústiza, Leire Zubiaurre, Ma. Dolores De Juan, Pedro Otazua, Eva Zapata, and Agustin Castiella
- Subjects
Male ,Pediatrics ,DNA Mutational Analysis ,Specialties of internal medicine ,Gastroenterology ,Gene Frequency ,Outpatients ,Genotype ,Prospective Studies ,Prospective cohort study ,Aged, 80 and over ,biology ,Incidence ,General Medicine ,Middle Aged ,Magnetic Resonance Imaging ,Metabolic syndrome ,RC581-951 ,Female ,Hemochromatosis ,HFE gene ,MRI ,Adult ,medicine.medical_specialty ,Young Adult ,Internal medicine ,medicine ,Humans ,Hemochromatosis Protein ,Secondary Care Centers ,Allele frequency ,Aged ,Hepatology ,Transferrin saturation ,business.industry ,Histocompatibility Antigens Class I ,Membrane Proteins ,nutritional and metabolic diseases ,DNA ,medicine.disease ,Genotype frequency ,Ferritin ,Spain ,Ferritins ,Mutation ,biology.protein ,Hyperferritinemia ,business ,Body mass index - Abstract
Background and Aims. There are limited data on clinical and phenotypic characteristics of outpatients referred for hyperferritinemia (HF). To determine the causes of HF in outpatients referred to a secondary hospital.Material and methods. A prospective study of 132 consecutive patients with HF (> 200 μg/L, women; > 300 μg/L, men) was conducted from January-December 2010.Results. Mean age, 54.42 years (SD: 13.47, range: 23-83); body mass index (BMI), 28.80 (SD: 3.96, 17-39); ferritin (SF), 579.54 ng/mL (SD: 296.575, 206-1668); transferrin saturation (TSI), 43.87% (SD: 14.09, 12-95); iron (Fe), 134 μg/dL (SD: 49.68, 55-322); overweight: 48.31%, and obese: 40.44% (89%), and most patients were men (108/132). Regarding HFE mutations, H63D/H63D genotype and H63D allele frequencies were 17.5% (vs. 7.76% in controls); and 36% (31% in controls) respectively. While 63.6% consumed no alcohol, 18.1% consumed ≥ 60 g/day, the mean being 20.83 (SD: 33.95, 0-140). Overall, 6/132 (4.5%) patients were positive for B or C hepatitis. Mean LIC by MRI was 36.04 (SD: 32.78, 5-210), 53 patients having normal concentrations (< 36 µmol/g), 22 (33%) iron overload (37-80), and 4 (5%) high iron overload (> 80). Metabolic syndrome (MS) was detected in 44/80 men (55%) and 10/17 women (59%). In this group, the genotype frequency of the H63D/H63D mutation was significantly higher than in controls-21.56% vs. 7.76%- (p = 0.011); the H63D allelic frequency was 42.15% in MS group and 31% in controls (p = 0.027).Conclusion. The H63D/H63D genotype and H63D allele predispose individuals to HF and MS. MRI revealed iron overload in 33% of patients.
- Published
- 2015
20. Serum ferritin is a biomarker for liver mortality in the Hemochromatosis and Iron Overload Screening Study
- Author
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David A. Alter, Mark Speechley, James C. Barton, Paul C. Adams, and Helen Guo
- Subjects
Male ,medicine.medical_specialty ,Iron Overload ,Specialties of internal medicine ,Gastroenterology ,Liver disease ,Population screening ,Cause of Death ,Internal medicine ,Diabetes mellitus ,medicine ,Humans ,Mass Screening ,Survival analysis ,Hemochromatosis ,Mass screening ,Ontario ,Hepatology ,business.industry ,Transferrin saturation ,Proportional hazards model ,Hazard ratio ,General Medicine ,Middle Aged ,medicine.disease ,Surgery ,Survival Rate ,RC581-951 ,Ferritins ,Female ,Hyperferritinemia ,business ,Biomarkers - Abstract
Background. We identified no reports of long-term follow-up of participants in hemochromatosis screening programs. We evaluated causes of death and survival in non-C282Y homozygous Canadian participants in the primary care-based hemochromatosis and iron overload screening (HEIRS) study.Material and methods. Initial screening (IS) included transferrin saturation (TS), serum ferritin (SF), HFE genotyping (C282Y, H63D), and health questionnaire responses. By definition, participants without C282Y or H63D had HFE wt/wt. We linked 20,306 Canadian participants to the Ontario Death Registry for dates and causes of death 9 y after IS. We computed Cox proportional hazards to identify factors with increased death risks and Kaplan-Meier curves to estimate survival of non-C282Y homozygous participants with SF ≤ 1,000 µg/L and > 1,000 µg/dL.Results. There were 19,052 evaluable participants (IS mean age 49 y; 60% women; 93 C282Y homozygotes). There were 988 deaths. Significantly increased hazard ratios for all-cause mortality were positively associated with TS, SF, men, and C282Y homozygosity, and liver disease, diabetes, and heart failure reports. Non-C282Y homozygous participants with SF > 1,000 µg/L had lower survival than those with SF ≤ 1,000 µg/L (p < 0.0001).Conclusions. Nine years after initial screening, non-C282Y homozygous participants and SF > 1,000 µg/L was associated with decreased survival.
- Published
- 2015
21. Hemophagocytic Lymphohistiocytosis in the Emergency Department: Recognizing and Evaluating a Hidden Threat.
- Author
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Morrissette K, Bridwell R, Lentz S, Brem E, Gutierrez KO, Singh M, Koyfman A, and Long B
- Subjects
- COVID-19, Emergency Service, Hospital, Humans, Splenomegaly etiology, Lymphohistiocytosis, Hemophagocytic diagnosis
- Abstract
Background: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hematologic disorder resulting from an ineffective and pathologic activation of the immune response system that may mimic common emergency department presentations, including sepsis, acute liver failure, disseminated intravascular coagulation, and flu-like illnesses such as coronavirus disease 2019 (COVID-19)., Objective: This narrative review provides a summary of the disease and recommendations for the recognition and diagnostic evaluation of HLH with a focus on the emergency clinician., Discussion: Though the condition is rare, mortality rates are high, ranging from 20% to 80% and increasing with delays in treatment. Importantly, HLH has been recognized as a severe variation of the cytokine storm associated with COVID-19. Common features include a history of infection or malignancy, fever, splenomegaly or hepatomegaly, hyperferritinemia, cytopenias, coagulopathies, abnormal liver enzymes, and hypertriglyceridemia. Using specific features of the history, physical examination, laboratory studies, and tools such as the HScore, HLH-2004/2009, and hyperferritinemia thresholds, the emergency clinician can risk-stratify patients and admit for definitive testing. Once diagnosed, disease specific treatment can be initiated., Conclusion: This review describes the relevant pathophysiology, common presentation findings, and a framework for risk stratification in the emergency department., (Published by Elsevier Inc.)
- Published
- 2021
- Full Text
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22. Narrative Review of Hyperferritinemia, Iron Deficiency, and the Challenges of Managing Anemia in Aboriginal and Torres Strait Islander Australians With CKD.
- Author
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Majoni SW, Lawton PD, Rathnayake G, Barzi F, Hughes JT, and Cass A
- Abstract
Aboriginal and Torres Strait Islander Australians (Indigenous Australians) suffer some of the highest rates of chronic kidney disease (CKD) in the world. Among Indigenous Australians in remote areas of the Northern Territory, prevalence rates for renal replacement therapy (RRT) are up to 30 times higher than national prevalence. Anemia among patients with CKD is a common complication. Iron deficiency is one of the major causes. Iron deficiency is also one of the key causes of poor response to the mainstay of anemia therapy with erythropoiesis-stimulating agents (ESAs). Therefore, the effective management of anemia in people with CKD is largely dependent on effective identification and correction of iron deficiency. The current identification of iron deficiency in routine clinical practice is dependent on 2 surrogate markers of iron status: serum ferritin concentration and transferrin saturation (TSAT). However, questions exist regarding the use of serum ferritin concentration in people with CKD because it is an acute-phase reactant that can be raised in the context of acute and chronic inflammation. Serum ferritin concentration among Indigenous Australians receiving RRT is often markedly elevated and falls outside reference ranges within most national and international guidelines for iron therapy for people with CKD. This review explores published data on the challenges of managing anemia in Indigenous people with CKD and the need for future research on the efficacy and safety of treatment of anemia of CKD in patients with high ferritin and evidence iron deficiency., (© 2020 International Society of Nephrology. Published by Elsevier Inc.)
- Published
- 2020
- Full Text
- View/download PDF
23. [Gaucher Disease type 1 mimicking immune thrombocytopenia: Role of hyperferritinemia and hypergammaglobulinemia in the initial evaluation of an isolated thrombopenia].
- Author
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Faucher B, Seguier J, Swiader L, Cuquemelle C, Cerutti D, and Ebbo M
- Subjects
- Adult, Diagnosis, Differential, Female, Ferritins blood, Gaucher Disease blood, Humans, Hypergammaglobulinemia diagnosis, Iron Metabolism Disorders diagnosis, Pregnancy, Pregnancy Complications, Hematologic blood, Splenomegaly etiology, Thrombocytopenia complications, Thrombocytopenia immunology, Gaucher Disease diagnosis, Thrombocytopenia diagnosis
- Abstract
Introduction: Gaucher disease type 1 is a rare genetic disease. It can cause thrombocytopenia. Current guidelines do not support bone marrow examination in front of isolated thrombocytopenia if no evidence suggests malignant hemopathy. This strategy aiming at sparing unnecessary investigations makes such rare diseases more difficult to diagnose., Case Report: A 31-year-old woman was diagnosed with immune thrombocytopenia according to current guidelines. She presented later with mild splenomegaly. Bone marrow aspirate smears showed Gaucher cells. Gaucher disease was then confirmed. Looking backward, initial biological clues (hyperferritinemia, hypergammaglobulinemia) should have enabled to consider the diagnosis., Conclusion: Gaucher disease type 1 can be responsible for apparently isolated thrombocytopenia. The disease must be looked for if the thrombocytopenia is associated with unexplained hypergammaglobulinemia or hyperferritinemia. Diagnosing immune thrombocytopenia without bone marrow sample requires to systematically pay attention to any clinical or biological abnormality, not to ignore rare differential diagnoses., (Copyright © 2019 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)
- Published
- 2019
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- View/download PDF
24. 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
- Author
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Vasiliki Liakouli, Roberto Giacomelli, Francesco Ciccia, Francesco Carubbi, Piero Ruscitti, Paola Di Benedetto, Paola Cipriani, Giovanni Triolo, Onorina Berardicurti, Aroldo Rizzo, Ruscitti, P., Cipriani, P., Di Benedetto, P., Ciccia, F., Liakouli, V., Carubbi, F., Berardicurti, O., Rizzo, A., Triolo, G., Giacomelli, R., Ciccia, Francesco, and Triolo, Giovanni
- Subjects
Adult-Onset ,Adult ,Pathology ,medicine.medical_specialty ,Apoferritin ,Immunology ,Adult-onset Still's disease ,Hyperferritinemia ,Macrophage activation syndrome ,Age of Onset ,Animals ,Apoferritins ,Bone Marrow ,Humans ,Liver ,Macrophage Activation Syndrome ,Still's Disease, Adult-Onset ,Immunology and Allergy ,Medicine (all) ,Immunofluorescence ,Biopsy ,medicine ,medicine.diagnostic_test ,biology ,CD68 ,business.industry ,Animal ,medicine.disease ,Still's Disease ,Ferritin ,medicine.anatomical_structure ,Liver biopsy ,biology.protein ,Immunohistochemistry ,Bone marrow ,business ,Human - 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.
- Published
- 2015
25. Significance of Hyperferritinemia in Hospitalized Adults.
- Author
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Schaffner M, Rosenstein L, Ballas Z, and Suneja M
- Subjects
- Adult, Aged, Female, Humans, Iowa epidemiology, Lymphohistiocytosis, Hemophagocytic etiology, Macrophage Activation Syndrome etiology, Male, Middle Aged, Retrospective Studies, Ferritins metabolism, Iron Overload complications, Iron Overload diagnosis, Lymphohistiocytosis, Hemophagocytic epidemiology, Macrophage Activation Syndrome epidemiology
- Abstract
Background: Although high ferritin levels are associated with iron overload, it is known that ferritin is also an acute-phase reactant that may be elevated in conditions associated with acute and chronic inflammation. In addition, an elevated ferritin level is a criterion for the diagnosis of hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS). Therefore, the significance of elevated serum ferritin is often unclear. As HLH/MAS is a medical emergency, prompt diagnosis is important to guide appropriate treatment., Materials and Methods: To study the spectrum of diagnoses associated with elevated serum ferritin, we did a retrospective review of adult patients admitted to our academic medical center from 2008-2012 with serum ferritin levels greater than 2,000ng/mL. The degree of hyperferritinemia was compared to different diagnoses and selected laboratory values., Results: A total of 333 patients were identified with a serum ferritin level >2,000ng/mL. Hepatocellular injury was the most prevalent diagnosis with n = 126; infection was next with n = 96. Eleven patients were diagnosed with HLH/MAS., Conclusions: Elevated ferritin, as an isolated finding, was not a specific marker for the diagnosis of HLH/MAS. However, as a group, HLH/MAS patients had the highest mean and median ferritin values., (Published by Elsevier Inc.)
- Published
- 2017
- Full Text
- View/download PDF
26. Disease progression and oxidative stress are associated with higher serum ferritin levels in patients with multiple sclerosis.
- Author
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Ferreira KPZ, Oliveira SR, Kallaur AP, Kaimen-Maciel DR, Lozovoy MAB, de Almeida ERD, Morimoto HK, Mezzaroba L, Dichi I, Reiche EMV, and Simão ANC
- Subjects
- Adult, Biomarkers blood, Body Mass Index, Disability Evaluation, Disease Progression, Female, Humans, Immunologic Factors therapeutic use, Iron blood, Logistic Models, Luminescence, Male, Multiple Sclerosis drug therapy, Multivariate Analysis, Smoking blood, Ferritins blood, Multiple Sclerosis blood, Oxidative Stress physiology
- Abstract
Hyperferritinemia and oxidative stress have been implicated in the pathogenesis of multiple sclerosis (MS). The aim of the present study was to evaluate the serum levels of ferritin and to verify their association with oxidative stress markers and MS progression. This study included 164 MS patients, which were divided in two groups according to their levels of ferritin (cut off 125.6μg/L). Oxidative stress was evaluated by tert-butyl hydroperoxide-initiated chemiluminescence (CL-LOOH), advanced oxidation protein products (AOPP), carbonyl protein, nitric oxide metabolites (NO
x ), sulfhydryl groups of protein and total radical-trapping antioxidant parameter (TRAP). MS patients with elevated levels of ferritin showed higher disease progression (p=0.030), AOPP (p=0.001), and lower plasma NOx levels (p=0.031) and TRAP (p=0.006) than MS patients with lower ferritin levels. The multivariate binary logistic regression analysis showed that increased AOPP and progression of disease were significantly and positively associated with increase of ferritin. The combination of serum ferritin levels and oxidative stress markers were responsible for 13,9% in the disease progression. In conclusion, our results suggest that ferritin could aggravate oxidative stress in patients with MS and contribute to progression of disease., (Copyright © 2016 Elsevier B.V. All rights reserved.)- Published
- 2017
- Full Text
- View/download PDF
27. Hemophagocytic syndromes (HPSs) including hemophagocytic lymphohistiocytosis (HLH) in adults: A systematic scoping review.
- Author
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Hayden A, Park S, Giustini D, Lee AY, and Chen LY
- Subjects
- Combined Modality Therapy, Disease Susceptibility, Humans, Lymphohistiocytosis, Hemophagocytic epidemiology, Lymphohistiocytosis, Hemophagocytic etiology, Practice Guidelines as Topic, Prognosis, Treatment Outcome, Lymphohistiocytosis, Hemophagocytic diagnosis, Lymphohistiocytosis, Hemophagocytic therapy
- Abstract
Most knowledge of hemophagocytic syndromes (HPSs) including hemophagocytic lymphohistiocytosis (HLH) is derived from pediatric studies; literature on adult HPS/HLH predominantly consists of small retrospective studies with clinical and methodological heterogeneity. The aims of this systematic scoping review were to provide an overview of existing literature on adult HPS/HLH, describe current practices in diagnosis and treatment, and propose priorities for future research. Articles from Ovid Medline, Embase and Pubmed (1975-2015) describing 10 or more unique adults (age>15years) with HPS/HLH were included. 82 publications were eligible: 10 were prospective and 72 were retrospective. Of the six distinct diagnostic criteria, the HLH-2004 criteria were by far the most commonly used. A minority of studies tested for genetic abnormalities (12), soluble interleukin-2 receptor (11), and/or NK function (11) in a subset of patients. Most centers used steroids and either etoposide-based (HLH-94/HLH-2004) or doxorubicin-based (CHOP) initial therapy regimens. Allogeneic hematopoietic cell therapy for treatment of adult HLH has rarely been reported. Mortality in larger treatment focused studies ranged from 20 to 88%. Developing adult-specific diagnostic criteria based on widely evaluable features of secondary HPS/HLH and establishing standard initial therapies are priorities for future research., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2016
- Full Text
- View/download PDF
28. [Diagnosis of an increased serum level of ferritin].
- Author
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Lorcerie B, Audia S, Samson M, Millière A, Falvo N, Leguy-Seguin V, Berthier S, and Bonnotte B
- Subjects
- Humans, Iron Metabolism Disorders complications, Iron Metabolism Disorders etiology, Ferritins blood, Iron Metabolism Disorders blood, Iron Metabolism Disorders diagnosis
- Abstract
The discovery of a hyperferritinemia is most of the time fortuitous. The diagnostic approach aims at looking for the responsible etiology and at verifying if an iron hepatic overload is present or not. Three diagnostic steps are proposed. The clinical elements and a few straightforward biological tests are sufficient at first to identify one of the four main causes: alcoholism, inflammatory syndrome, cytolysis, and metabolic syndrome. None of these causes is associated with a significant iron hepatic overload. If the transferring saturation coefficient is raised (>50%) a hereditary hemochromatosis should be discussed. Secondly, less common disorders will be discussed. Among these, only the chronic hematological disorders either acquired or congenital are at risk of iron hepatic overload. Thirdly, if a doubt persists in the etiologic research, and the serum ferritin level is very high or continues to rise, it is essential to verify that there is no iron hepatic overload. For that purpose, the MRI with study of the iron overload is the main test, which will guide the therapeutic attitude. Identification of more than a single etiology occurs in more than 40% of the cases., (Copyright © 2015. Published by Elsevier SAS.)
- Published
- 2015
- Full Text
- View/download PDF
29. 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.
- Author
-
Ruscitti P, Cipriani P, Di Benedetto P, Ciccia F, Liakouli V, Carubbi F, Berardicurti O, Rizzo A, Triolo G, and Giacomelli R
- Subjects
- Adult, Age of Onset, Animals, Apoferritins metabolism, Humans, Apoferritins analysis, Bone Marrow chemistry, Liver chemistry, Macrophage Activation Syndrome metabolism, Still's Disease, Adult-Onset metabolism
- 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., (Copyright © 2015 Elsevier B.V. All rights reserved.)
- Published
- 2015
- Full Text
- View/download PDF
30. A hyper-ferritinemia syndrome evolving in recurrent macrophage activation syndrome, as an onset of amyopathic juvenile dermatomyositis: a challenging clinical case in light of the current diagnostic criteria.
- Author
-
Poddighe D, Cavagna L, Brazzelli V, Bruni P, and Marseglia GL
- Subjects
- Adolescent, Age of Onset, Humans, Recurrence, Skin pathology, Dermatomyositis diagnosis, Macrophage Activation Syndrome diagnosis
- Abstract
Juvenile dermatomyositis is an immune-mediated inflammatory multi-system disease involving mainly striated muscles and skin. Typical dermatological features are fundamental to establish the diagnosis, especially whenever the myopathy is very mild or absent, as it occurs in the form called as amyopathic juvenile dermatomyositis. Sometimes, systemic rheumatic diseases can develop a hyperferritinemia syndrome characterized by hemophagocytosis, namely macrophage activation syndrome, which represents a severe and life-threatening complication. Here, we describe a complex clinical history characterized by a hyper-ferritinemia syndrome after infectious mononucleosis, leading to recurrent episodes of macrophage activation syndrome. Finally, the late onset of several skin changes brought to a diagnosis of amyopathic juvenile dermatomyositis., (Copyright © 2014 Elsevier B.V. All rights reserved.)
- Published
- 2014
- Full Text
- View/download PDF
31. Adult-onset Still's disease.
- Author
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Gerfaud-Valentin M, Jamilloux Y, Iwaz J, and Sève P
- Subjects
- Adaptive Immunity, Adult, Genetic Predisposition to Disease, Humans, Immunity, Innate, Prognosis, Still's Disease, Adult-Onset diagnosis, Still's Disease, Adult-Onset drug therapy, Still's Disease, Adult-Onset genetics, Still's Disease, Adult-Onset immunology
- Abstract
First described in 1971, adult-onset Still's disease (AOSD) is a rare multisystemic disorder considered as a complex (multigenic) autoinflammatory syndrome. A genetic background would confer susceptibility to the development of autoinflammatory reactions to environmental triggers. Macrophage and neutrophil activation is a hallmark of AOSD which can lead to a reactive hemophagocytic lymphohistiocytosis. As in the latter disease, the cytotoxic function of natural killer cells is decreased in patients with active AOSD. IL-18 and IL-1β, two proinflammatory cytokines processed through the inflammasome machinery, are key factors in the pathogenesis of AOSD; they cause IL-6 and Th1 cytokine secretion as well as NK cell dysregulation leading to macrophage activation. The clinico-biological picture of AOSD usually includes high spiking fever with joint symptoms, evanescent skin rash, sore throat, striking neutrophilic leukocytosis, hyperferritinemia with collapsed glycosylated ferritin (<20%), and abnormal liver function tests. According to the clinical presentation of the disease at diagnosis, two AOSD phenotypes may be distinguished: i) a highly symptomatic, systemic and feverish one, which would evolve into a systemic (mono- or polycyclic) pattern; ii) a more indolent one with arthritis in the foreground and poor systemic symptomatology, which would evolve into a chronic articular pattern. Steroid- and methotrexate-refractory AOSD cases benefit now from recent insights into autoinflammatory disorders: anakinra seems to be an efficient, well tolerated, steroid-sparing treatment in systemic patterns; tocilizumab seems efficient in AOSD with active arthritis and systemic symptoms while TNFα-blockers could be interesting in chronic polyarticular refractory AOSD., (Copyright © 2014 Elsevier B.V. All rights reserved.)
- Published
- 2014
- Full Text
- View/download PDF
32. Serum ferritin predicts early mortality in patients with decompensated cirrhosis.
- Author
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Maiwall R, Kumar S, Chaudhary AK, Maras J, Wani Z, Kumar C, Rastogi A, Bihari C, Vashisht C, and Sarin SK
- Subjects
- Adult, Aged, Biomarkers blood, Cohort Studies, Female, Humans, India epidemiology, Kaplan-Meier Estimate, Male, Middle Aged, Prognosis, Proportional Hazards Models, Retrospective Studies, Ferritins blood, Liver Cirrhosis blood, Liver Cirrhosis mortality
- Abstract
Background & Aims: Serum ferritin is a known marker of hepatic necro-inflammation and has been studied to predict 1 year mortality and post-transplant survival in decompensated cirrhotics. However, there are no studies evaluating ferritin as a predictor of early mortality. We investigated whether serum ferritin levels could predict 15 day and 30 day mortality in patients with decompensated cirrhosis., Methods: 318 patients with decompensated cirrhosis were included., Results: Patients of decompensated cirrhosis [257 males, mean age of 51 [±13]years, were followed for a median of 31 days. Serum ferritin levels were significantly different between survivors and non-survivors [p<0.001] and showed significant correlation with MELD score [p<0.001], CTP score [p<0.001], leucocyte counts [TLC] [p<0.001], serum sodium [p<0.001], ACLF grades [p=0.005], spontaneous bacterial peritonitis [SBP] [p=0.02], hepatic encephalopathy [HE] [p<0.001] and hepatorenal syndrome [HRS] [p=0.012]. Serum ferritin, etiology, MELD, HE, CTP score, sodium, TLC, and ACLF grades were significant predictors of mortality on univariate analysis. Ferritin [p=0.04, HR 1.66 95% CI (1.02-2.73)] was a significant predictor of early mortality on multivariate analysis along with HE [p=0.006, HR 3.47 95% CI (2.13-8.41)] (Model 1), TLC [p=0.02, HR 1.81 95% CI (1.06-3.07)] (Model 2), ACLF grades [p=0.018, HR 2.013,95% CI (1.126-3.60)], and CTP score [p<0.0001, HR 1.36 95% CI (1.17-1.59)] (Model 3)., Conclusion: Serum ferritin levels correlate with severity of hepatic decompensation and are associated with early liver related death independent of the MELD score in hospitalized patients with decompensated cirrhosis. This could also have a potential therapeutic implication., (Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)
- Published
- 2014
- Full Text
- View/download PDF
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