Hepcidin Independent Anemia of Inflammation

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2050-2050
Author(s):  
Seth Rivera ◽  
Sophie Vaulont ◽  
Dana Shprung ◽  
Donald Limbrick ◽  
Tomas Ganz
Keyword(s):  
Regulatory Protein ◽  
Connective Tissue Diseases ◽  
Future Research ◽  
Common Complication ◽  
Mycobacterial Disease ◽  
Advisory Committees ◽  
Anemia Of Chronic Disease ◽  
Inflammatory Conditions ◽  
Iron Sequestration ◽  
Anemia Of Inflammation

Abstract Abstract 2050 Anemia of inflammation (AI, anemia of chronic disease) is a common complication of a wide variety of inflammatory conditions including infections and connective tissue diseases. Because the iron regulatory protein hepcidin is increased during inflammation and overexpression of hepcidin recapitulates many of the features of AI, hepcidin is currently believed to be the primary mediator of AI. Furthermore, Sasu and colleagues showed that blocking hepcidin could improve AI (Blood, Vol. 115, No. 17, pp. 3616-24). To test whether hepcidin is indeed necessary for the development of AI, we used two models of AI in hepcidin knockout mice. The first model, using heat-killed Brucella abortus to model brucellosis, is the same as that used by Sasu and colleagues. The second model uses complete Freund's adjuvant to model Mycobacterial disease. We showed that absence of hepcidin did not protect against the development of anemia. Furthermore, we show that this was an iron restricted anemia arguing that iron sequestration can occur independent of hepcidin. This study indicates that hepcidin may not be the central mediator in all AI. Future research will be needed to determine why the anti-hepcidin treatment used by Sasu and colleagues was able to improve the anemia. Disclosures: Ganz: Intrinsic Life Sciences: Employment, Membership on an entity's Board of Directors or advisory committees.

scholarly journals Health system wide “big data” analysis of rheumatologic conditions and scleritis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Meghan K. Berkenstock ◽  
Andrew R. Carey
Keyword(s):  
Relative Risk ◽  
Health System ◽  
Systemic Disease ◽  
Autoimmune Disorder ◽  
Future Research ◽  
Inflammatory Conditions ◽  
Autoimmune Conditions ◽  
Icd 10 ◽  
Autoimmune Condition ◽  
Referral Bias

Abstract Background The development of scleritis in the setting of autoimmune conditions has been well documented. Prior series have assessed the relationship between systemic autoimmune disorders and scleritis only in patients referred for rheumatologic or ocular inflammation. This can lead to a referral bias. We reviewed all charts within the electronic medical record (EMR) of a health system for patients with systemic autoimmune and scleritis diagnoses to determine the prevalence of both and which disorders had the highest relative risk of developing scleritis. Methods The EMR was searched for scleritis and systemic inflammatory diagnoses in the past medical history and diagnosis tabs, and for associated disease specific laboratory values. The intersection of scleritis and systemic inflammatory conditions was assessed through searching both SNOMED Clinical Terminology and ICD-10 codes for diagnoses. The prevalence of each autoimmune disorder, scleritis prevalence, the percentage of patients with an autoimmune condition having scleritis, the percentage of patients with scleritis having an autoimmune condition; the relative risk (RR) of scleritis patients having a specific autoimmune disorder were calculated. Results A total of 5.9 million charts were searched with autoimmune conditions identified in 148,993 patients. The most common autoimmune conditions overall were HLA-B27-associated diseases (n = 26,680; prevalence 0.45%); rheumatoid arthritis (RA)(N = 19,923; prevalence 0.34%). Conversely, 2702 patients were identified with scleritis (prevalence 0.05%), of which 31.4% had an associated autoimmune condition. Patients with RA represented the highest percentage of patients with an autoimmune condition having scleritis. Granulomatosis with polyangiitis (GPA) represented the highest the percentage of patients with scleritis having an autoimmune condition. Sjogrens was the third most common condition associated with scleritis- making up 4.5% of cases. An association with juvenile idiopathic arthritis (JIA) was seen in 0.3% of patients. Conclusions While this is the largest retrospective review examining the association between autoimmune disease and scleritis, the findings are similar to prior studies with nearly a third of scleritis patients having an underlying autoimmune diagnosis. Limitations of the study included accurate chart coding; having laboratory results within the searchable EMR. Future research is needed to delineate associations of systemic disease with the anatomic location of scleritis using EMR.

scholarly journals P051 Symptoms of COVID-19 and anxiety levels in adult patients receiving b-and ts-DMARDS using an online reporting system

Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_1) ◽  
Author(s):  
May Nwe Lwin ◽  
Christopher Holroyd ◽  
Dinny Wallis ◽  
Saul Faust ◽  
Hans De Graaf ◽  
...  
Keyword(s):  
Lupus Erythematosus ◽  
Joint Pain ◽  
Connective Tissue Diseases ◽  
Anxiety Score ◽  
Online Portal ◽  
Inflammatory Conditions ◽  
Advanced Therapy ◽  
Number Of Patients ◽  
Patient Reported ◽  
Anxiety Levels

Abstract Background/Aims  The coronavirus disease-2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for over 120,000 UK deaths. Those with chronic inflammatory conditions or receiving immunosuppressive medications are at higher risk of COVID-19 than the general population. As a result, rheumatology patients taking b- or ts-DMARDs were advised to shield. We planned to observe COVID-19 related symptoms and anxiety levels reported by rheumatology patients during the pandemic. Methods  From April 2020, 1,004 rheumatology patients from an advanced therapy database were invited to participate in the adult ImmunoCOVID study to collect daily symptoms (fever, cough, shortness of breath (SOB), sore throat, blocked nose, red-eye, headache, fatigue, joint pain, muscle pain, chills, nausea, diarrhoea and vomiting, loss of senses) and anxiety level using an online portal. Loss of senses were not recorded until week 7 as these were not officially recognized at the pandemic onset. Results  153 patients (rheumatoid arthritis, n = 75, psoriatic arthritis, n = 28, Axial spondyloarthropathy, n = 24, systemic lupus erythematosus, n = 2 and other connective tissue diseases, n = 24) consented and participated. By week 25, 142 patients remained. Among those, 36.57% (±6.09%) (average (±SD)) reported no symptoms over the 25 week period. The main symptoms reported were joint pain (mean=47.94%) followed by fatigue (27.17%). Few patients reported fever (0.94%), cough (8.34%), SOB (4.53%), or loss of senses (1.11%) with more symptoms reported during the first 8 weeks (April/May 2020) and another increase in September/October 2020. The anxiety score (pragmatic 10-point scale) mean (±SD) was 5.60 (±0.34) and remained elevated throughout the study though higher when lockdown began. Conclusion  During the first peak of SARS-CoV-2, the number of patients reporting COVID-19 symptoms appeared high and was associated with high levels of anxiety. As only a small number have been swab-tested, this may suggest that larger numbers of untested individuals have had COVID-19 with mild symptoms. Features of inflammatory rheumatic illnesses may mimic COVID-19 symptoms and create diagnostic difficulty (joint pain and fatigue) whilst anxiety may lead to over-reporting of symptoms in the absence of infection. The key symptoms of fever, cough and SOB were less common and may be most reliable. Disclosure  M. Lwin: None. C. Holroyd: None. D. Wallis: None. S. Faust: None. H. De Graaf: None. C.J. Edwards: Honoraria; Abbvie, Biogen, BMS, Celgene, Fresenius, GSK, Janssen, Lilly, Mundipharma, Pfizer, Roche, Sanofi, UCB. Member of speakers’ bureau; Abbvie, Biogen, BMS, Celgene, Janssen, Lilly, Sanofi, Pfizer, Roche. Grants/research support; Abbvie, Biogen, Pfizer. P051 Table 1:patient reported symptoms and anxiety score from immunoCOVID studyWeek & (number of participants)Fever (%)Cough (%)SOB (%)Joint pain (%)Fatigue (%)Loss of senses (%)No symptoms (%)Tested (n)Test positive (n)Anxiety score1 (26)3.857.6911.5446.1530.77NA30.77006.312 (42)2.3311.639.3052.3834.88NA28.57005.833 (69)1.4514.494.3552.1737.68NA23.19415.884 (92)1.0911.966.5254.3531.52NA27.17206.225 (110)0.0011.716.3145.9533.33NA30.00006.156 (108)0.0010.193.7050.0026.85NA34.26205.747 (119)0.8410.084.2049.5828.57NA34.45205.938 (120)0.007.505.0051.6734.170.8329.17305.629 (124)0.817.263.2352.4229.840.8136.29405.6410 (118)0.008.473.3948.3129.660.8534.75205.2811 (116)0.858.476.7849.1529.661.6933.62305.6512 (131)0.006.114.5856.4926.720.7635.11205.4513 (110)0.916.362.7350.0029.091.8242.73105.4414 (121)0.837.442.4847.1125.620.8339.67805.2815 (100)1.007.003.0046.0023.001.0041.00405.4816 (114)0.887.893.5139.4725.441.7542.98905.2717 (105)0.008.573.8144.7622.860.9543.81425.1018 (107)0.006.543.7443.9319.630.9343.93405.3019 (99)0.005.052.0240.4019.191.0145.45505.0820 (110)0.914.552.7350.9124.550.9139.09NA0Missing data21 (106)0.946.602.8350.0020.750.9439.62405.2822 (104)2.889.626.7349.0430.770.9635.58305.5023 (106)1.897.553.7742.4526.420.9436.79805.8924 (108)0.938.332.7844.4422.220.9341.67605.6125 (94)1.067.454.2641.4915.962.1344.68605.49Average0.948.344.5347.9427.171.1136.575.60SD0.972.312.254.395.350.426.090.34Weekly data are the average of daily reported symptoms and anxiety levels.

Anemia of Chronic Disease (Anemia of Inflammation)

2009 ◽  
Vol 122 (2-3) ◽  
pp. 103-108 ◽  
Author(s):  
Neeraj Agarwal ◽  
Josef T. Prchal
Keyword(s):  
Chronic Disease ◽  
Anemia Of Chronic Disease ◽  
Anemia Of Inflammation

scholarly journals Transcriptome and proteome of the corm, leaf and flower of Hypoxis hemerocallidea (African potato)

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0253741
Author(s):  
Mihai-Silviu Tomescu ◽  
Selisha Ann Sooklal ◽  
Thuto Ntsowe ◽  
Previn Naicker ◽  
Barbara Darnhofer ◽  
...  
Keyword(s):  
De Novo ◽  
Differential Expression Analysis ◽  
Terpene Synthase ◽  
Future Research ◽  
Terpene Synthases ◽  
Illumina Hiseq ◽  
Prostate Hyperplasia ◽  
Inflammatory Conditions ◽  
Urinary Infections ◽  
Hypoxis Hemerocallidea

The corm of Hypoxis hemerocallidea, commonly known as the African potato, is used in traditional medicine to treat several medical conditions such as urinary infections, benign prostate hyperplasia, inflammatory conditions and testicular tumours. The metabolites contributing to the medicinal properties of H. hemerocallidea have been identified in several studies and, more recently, the active terpenoids of the plant were profiled. However, the biosynthetic pathways and the enzymes involved in the production of the terpene metabolites in H. hemerocallidea have not been characterised at a transcriptomic or proteomic level. In this study, total RNA extracted from the corm, leaf and flower tissues of H. hemerocallidea was sequenced on the Illumina HiSeq 2500 platform. A total of 143,549 transcripts were assembled de novo using Trinity and 107,131 transcripts were functionally annotated using the nr, GO, COG, KEGG and SWISS-PROT databases. Additionally, the proteome of the three tissues were sequenced using LC-MS/MS, revealing aspects of secondary metabolism and serving as data validation for the transcriptome. Functional annotation led to the identification of numerous terpene synthases such as nerolidol synthase, germacrene D synthase, and cycloartenol synthase amongst others. Annotations also revealed a transcript encoding the terpene synthase phytoalexin momilactone A synthase. Differential expression analysis using edgeR identified 946 transcripts differentially expressed between the three tissues and revealed that the leaf upregulates linalool synthase compared to the corm and the flower tissues. The transcriptome as well as the proteome of Hypoxis hemerocallidea presented here provide a foundation for future research.

Anemia: Production Defects Generally Associated with a Normal or Largely Normal Bone Marrow

2017 ◽  
Author(s):  
Nancy Berliner ◽  
John M Gansner
Keyword(s):  
Bone Marrow ◽  
Differential Diagnosis ◽  
Chronic Disease ◽  
Blood Cells ◽  
Deficiency Anemia ◽  
Normal Bone Marrow ◽  
Peripheral Smear ◽  
Anemia Of Chronic Disease ◽  
Normal Bone ◽  
Anemia Of Inflammation

This review focuses on anemia resulting from production defects generally associated with a normal or largely normal bone marrow. The definition, epidemiology, etiology, pathogenesis, diagnosis, differential diagnosis, management, complications, and prognosis of the following production defects are discussed: Anemia of inflammation (AI; formerly known as anemia of chronic disease), and anemia in kidney disease, as well as anemia secondary to other conditions such as alchohol abuse and starvation. Iron deficiency anemia (IDA) is discussed elsewhere in this publication.  A figure depicts peripheral smear changes in the size and shape of red blood cells seen in starvation. A table lists the differential diagnoses of hypochromic anemias. This review contains 1 figure; 1 table; 79 references

Clinical Insights About Topical Treatment of Mild-to-Moderate Pediatric and Adult Atopic Dermatitis

2019 ◽  
Vol 23 (3_suppl) ◽  
pp. 3S-13S ◽  
Author(s):  
Charles W. Lynde ◽  
James Bergman ◽  
Loretta Fiorillo ◽  
Lyn Guenther ◽  
Jill Keddy-Grant ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Calcineurin Inhibitors ◽  
Skin Condition ◽  
Future Research ◽  
Barrier Dysfunction ◽  
Psychosocial Burden ◽  
Epidermal Barrier ◽  
Topical Corticosteroids ◽  
Topical Calcineurin Inhibitors ◽  
Inflammatory Conditions

Atopic dermatitis (AD) is a chronic inflammatory skin condition, also referred to as atopic eczema, that is identified by itching and recurrent eczematous lesions. It often starts in infancy where it affects up to 20% of children but is also highly prevalent in adults. AD inflicts a significant psychosocial burden on patients and their families and increases the risk of other immune-mediated inflammatory conditions, such as asthma and allergic rhinitis, food allergy, and mental health disorders. It is a lifelong condition associated with epidermal barrier dysfunction and altered immune function. Through the use of emollients and anti-inflammatory agents, current prevention and treatment therapies attempt to restore epidermal barrier function. Acute flares are treated with topical corticosteroids. Topical calcineurin inhibitors (TCIs) and topical corticosteroids (TCSs) are used for proactive treatment to prevent remission. There remains a need and opportunity to improve AD care through future research directed toward an improved understanding of the heterogeneity of the disease and its subtypes, the role of autoimmunity in its pathogenesis, the mechanisms behind disease-associated itch and response to specific allergens, and the comparative effectiveness and safety of therapies.

scholarly journals Iron Sequestration and Anemia of Inflammation

2009 ◽  
Vol 46 (4) ◽  
pp. 387-393 ◽  
Author(s):  
Tomas Ganz ◽  
Elizabeta Nemeth
Keyword(s):  
Iron Sequestration ◽  
Anemia Of Inflammation

scholarly journals Unexplained Aspects of Anemia of Inflammation

2010 ◽  
Vol 2010 ◽  
pp. 1-5 ◽  
Author(s):  
Elizabeth A. Price ◽  
Stanley L. Schrier
Keyword(s):  
Inflammatory Diseases ◽  
Deficiency Anemia ◽  
Red Cell ◽  
Regulatory Peptide ◽  
Anemia Of Chronic Disease ◽  
Erythropoietin Production ◽  
Red Cell Survival ◽  
Anemia Of Chronic Inflammation ◽  
Anemia Of Inflammation

Anemia of inflammation (AI), also known as anemia of chronic inflammation or anemia of chronic disease was described over 50 years ago as anemia in association with clinically overt inflammatory disease, and the findings of low plasma iron, decreased bone marrow sideroblasts and increased reticuloendothelial iron. Pathogenic features underlying AI include a mild shortening of red cell survival, impaired erythropoietin production, blunted responsiveness of the marrow to erythropoietin, and impaired iron metabolism mediated by inflammatory cytokines and the iron regulatory peptide, hepcidin. Despite marked recent advances in understanding AI, gaps remain, including understanding of the pathogenesis of AI associated with “noninflammatory” or mildly inflammatory diseases, the challenge of excluding iron deficiency anemia in the context of concomitant inflammation, and understanding more precisely the contributory role of hepcidin in the development of AI in human inflammatory diseases.

Anemia of Chronic Disease: Epidemiology and Pathophysiological Mechanisms – Literature Review

2020 ◽  
Vol 2 (4) ◽  
Author(s):  
Abdulrahman Ismaiel ◽  
Nahlah Al Srouji
Keyword(s):  
Bone Marrow ◽  
Chronic Disease ◽  
Iron Absorption ◽  
Solid Organ Transplantation ◽  
Future Research ◽  
Solid Organ ◽  
Chronic Infections ◽  
Anemia Of Chronic Disease ◽  
Erythroid Progenitor ◽  
Pathophysiological Mechanisms

Anemia of chronic disease (ACD), also known as anemia of inflammation (AI), is the term used to describe the hypoproliferative anemia. ACD was demonstrated in several conditions including systemic inflammation, acute and chronic infections of bacterial, viral, parasitic or fungal etiologies, cancer and hematological malignancies, chronic diseases such as chronic kidney disease and congestive heart failure, in addition to ageing, graft versus host disease after solid-organ transplantation, critical illness, and obesity. As a result of the possible different etiologies, the pathogenesis of ACD is complex with multiple pathways. Although the relationship between anemia, chronic inflammation and iron was discovered decades ago, only recently did research describe the role of several pro-inflammatory cytokines, in addition to molecular pathways and the type II acute-phase protein hepcidin involving iron absorption and metabolism, helping in the understanding of new pathophysiological mechanisms which were not previously understood that can lead to ACD. Hence, our understanding of the molecular mechanism related to intestinal iron absorption and metabolism has improved significantly. The pathophysiology of ACD is thought to be due to three main processes including a decreased erythrocyte survival that creates a demand for a mild increase in bone marrow production of erythrocytes, inability of the bone marrow to respond to the required increased demand due to an altered erythropoietin production or impaired ability to respond to erythropoietin by erythroid progenitor cells and alteration in iron stores’ mobilization through increased uptake and retention of iron in cells of the reticuloendothelial system. Lately, research advances including hepcidin’s discovery contributed to our understanding regarding iron metabolism and pathophysiological mechanisms in ACD. However, future research remains essential in order to find potential therapeutic strategies, possibly targeting genes coding cytokines to discover optimal therapies in treating ACD more efficiently.

Hepcidin Contributes to Anemia of Malignancy by Causing Sequestration of Iron in Hepatic Stores.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3197-3197
Author(s):  
Seth Rivera ◽  
Lide Liu ◽  
Elizabeta Nemeth ◽  
Victoria Gabayan ◽  
Tomas Ganz
Keyword(s):  
Serum Iron ◽  
Dry Weight ◽  
Lower Serum ◽  
Anemia Of Chronic Disease ◽  
Liver Iron ◽  
Median Serum ◽  
The Face ◽  
Bone Marrow Iron ◽  
Hepcidin Mrna ◽  
Anemia Of Inflammation

Abstract The iron regulatory hormone hepcidin is presumed to be the central mediator of anemia of inflammation (AI, anemia of chronic disease). Hepcidin is an acute phase protein which restricts iron absorption and release of iron from stores. Patients with hepatic adenomas producing large amounts of hepcidin had severe AI that resolved when the tumors were resected (Weinstein et al, 2002). In order to study the effects of hepcidin in anemia of malignancy, we created tumor xenografts in SCID mice, some of which were engineered to secrete large amounts of hepcidin (33 mice with control tumors, 30 with hepcidin producing tumors). Hepcidin producing tumors expressed 2000-times more hepcidin mRNA which also correlated with increased levels of hepcidin peptide detected in urine of these mice. Mice with hepcidin producing tumors were significantly more anemic (median hemoglobin = 10.4 vs. 8.4 g/dL, p=0.02) and had significantly lower serum iron values (median serum iron = 242 vs. 96 mg/dL, p<0.001). Liver iron was significantly higher in mice with hepcidin producing tumors (mean liver iron 199 vs. 142 mg/100 mg dry weight, p<0.001) even in the face of anemia and hypoferremia. Splenic and bone marrow iron levels were unchanged. Hepcidin contributes to the anemia of malignancy by sequestering iron predominately in hepatic stores, similar to the pattern seen in AI.

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