Decreased Hepcidin Levels Are Associated with Low Steady-state Hemoglobin in Children With Sickle Cell Disease in Tanzania
The contribution of hepcidin as a regulator of iron metabolism & erythropoiesis on the severity of anemia in sickle cell disease (SCD) remains poorly characterized, especially in Sub-Saharan African populations. The aims of the study were to determine if hepcidin is associated with severity of s...
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| Veröffentlicht in: | EBioMedicine 2018-08, Vol.34, p.158-164 |
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| creator | Lee, Nathaniel Makani, Julie Tluway, Furahini Makubi, Abel Armitage, Andrew E. Pasricha, Sant-Rayn Drakesmith, Hal Prentice, Andrew M. Cox, Sharon E. |
| description | The contribution of hepcidin as a regulator of iron metabolism & erythropoiesis on the severity of anemia in sickle cell disease (SCD) remains poorly characterized, especially in Sub-Saharan African populations. The aims of the study were to determine if hepcidin is associated with severity of steady-state anemia in SCD and to investigate factors associated with hepcidin and anemia in SCD.
Archived samples from 199 Tanzanian children, 56% boys aged 3–18 with laboratory-confirmed SCD were analysed based on recorded averaged steady-state hemoglobin (ASSH) quartiles (lowest vs. highest). Univariable and multivariable logistic regression was used to assess associations with ASSH quartiles.
In univariable analysis, hepcidin |
| doi_str_mv | 10.1016/j.ebiom.2018.07.024 |
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Archived samples from 199 Tanzanian children, 56% boys aged 3–18 with laboratory-confirmed SCD were analysed based on recorded averaged steady-state hemoglobin (ASSH) quartiles (lowest vs. highest). Univariable and multivariable logistic regression was used to assess associations with ASSH quartiles.
In univariable analysis, hepcidin <5·5 ng/mL was associated with increased odds of being in the lowest ASSH quartile (OR 2·20; 95%CI 1·2–3·93) but which was limited to girls (OR 4·85, 95%CI 1·79–13·09, p = .046 for interaction). In multivariable analyses including either reticulocyte percentage or erythropoietin, lower hepcidin remained significantly associated with lowest ASSH quartile, although the hepcidin-sex interaction no longer reached statistical significance. No associations with ASSH quartile were observed for markers of inflammation, hemolysis or potential iron markers except for microcytosis, associated with higher ASSH, but which was confounded by reticulocyte percentage and alpha-thalassaemia status.
Hepcidin is lower in more severely anaemic children with SCD independent of inflammation or markers of erythropoiesis.
Funding sources include The Wellcome Trust (080025, 095009, 094780 &070114), MRC-UK (MC-A760-5QX00), NIHR Oxford Biomedical Research Centre, and the Bill and Melinda Gates Foundation (“Hepcidin and Iron in Global Health”, OPP1055865).
•Low hepcidin levels are associated with severe anemia independent of markers of erythropoiesis and inflammation.•Low serum ferritin is present in some children but is not associated with severe anemia.•Although iron markers remain difficult to interpret in sickle cell disease, hepcidin levels were mostly below levels that would be expected to inhibit iron absorption and recycling.</description><identifier>ISSN: 2352-3964</identifier><identifier>EISSN: 2352-3964</identifier><identifier>DOI: 10.1016/j.ebiom.2018.07.024</identifier><identifier>PMID: 30056060</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Adolescent ; Anemia, Sickle Cell - blood ; Child ; Child, Preschool ; Female ; Hemoglobins - analysis ; Hepcidin ; Hepcidins - blood ; Humans ; Iron metabolism ; Male ; Nutrition ; Research Paper ; Severity of Illness Index ; Sickle cell anemia ; Sickle cell disease ; Sub-Saharan Africa ; Tanzania</subject><ispartof>EBioMedicine, 2018-08, Vol.34, p.158-164</ispartof><rights>2019 The Authors</rights><rights>Copyright © 2018. Published by Elsevier B.V.</rights><rights>2019 The Authors 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c459t-d8292c1fa18a7c3f91341a8784355d052f6fd73bdfefb97d51e3b1989eab1313</citedby><cites>FETCH-LOGICAL-c459t-d8292c1fa18a7c3f91341a8784355d052f6fd73bdfefb97d51e3b1989eab1313</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6116423/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6116423/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30056060$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lee, Nathaniel</creatorcontrib><creatorcontrib>Makani, Julie</creatorcontrib><creatorcontrib>Tluway, Furahini</creatorcontrib><creatorcontrib>Makubi, Abel</creatorcontrib><creatorcontrib>Armitage, Andrew E.</creatorcontrib><creatorcontrib>Pasricha, Sant-Rayn</creatorcontrib><creatorcontrib>Drakesmith, Hal</creatorcontrib><creatorcontrib>Prentice, Andrew M.</creatorcontrib><creatorcontrib>Cox, Sharon E.</creatorcontrib><title>Decreased Hepcidin Levels Are Associated with Low Steady-state Hemoglobin in Children With Sickle Cell Disease in Tanzania</title><title>EBioMedicine</title><addtitle>EBioMedicine</addtitle><description>The contribution of hepcidin as a regulator of iron metabolism & erythropoiesis on the severity of anemia in sickle cell disease (SCD) remains poorly characterized, especially in Sub-Saharan African populations. The aims of the study were to determine if hepcidin is associated with severity of steady-state anemia in SCD and to investigate factors associated with hepcidin and anemia in SCD.
Archived samples from 199 Tanzanian children, 56% boys aged 3–18 with laboratory-confirmed SCD were analysed based on recorded averaged steady-state hemoglobin (ASSH) quartiles (lowest vs. highest). Univariable and multivariable logistic regression was used to assess associations with ASSH quartiles.
In univariable analysis, hepcidin <5·5 ng/mL was associated with increased odds of being in the lowest ASSH quartile (OR 2·20; 95%CI 1·2–3·93) but which was limited to girls (OR 4·85, 95%CI 1·79–13·09, p = .046 for interaction). In multivariable analyses including either reticulocyte percentage or erythropoietin, lower hepcidin remained significantly associated with lowest ASSH quartile, although the hepcidin-sex interaction no longer reached statistical significance. No associations with ASSH quartile were observed for markers of inflammation, hemolysis or potential iron markers except for microcytosis, associated with higher ASSH, but which was confounded by reticulocyte percentage and alpha-thalassaemia status.
Hepcidin is lower in more severely anaemic children with SCD independent of inflammation or markers of erythropoiesis.
Funding sources include The Wellcome Trust (080025, 095009, 094780 &070114), MRC-UK (MC-A760-5QX00), NIHR Oxford Biomedical Research Centre, and the Bill and Melinda Gates Foundation (“Hepcidin and Iron in Global Health”, OPP1055865).
•Low hepcidin levels are associated with severe anemia independent of markers of erythropoiesis and inflammation.•Low serum ferritin is present in some children but is not associated with severe anemia.•Although iron markers remain difficult to interpret in sickle cell disease, hepcidin levels were mostly below levels that would be expected to inhibit iron absorption and recycling.</description><subject>Adolescent</subject><subject>Anemia, Sickle Cell - blood</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Female</subject><subject>Hemoglobins - analysis</subject><subject>Hepcidin</subject><subject>Hepcidins - blood</subject><subject>Humans</subject><subject>Iron metabolism</subject><subject>Male</subject><subject>Nutrition</subject><subject>Research Paper</subject><subject>Severity of Illness Index</subject><subject>Sickle cell anemia</subject><subject>Sickle cell disease</subject><subject>Sub-Saharan Africa</subject><subject>Tanzania</subject><issn>2352-3964</issn><issn>2352-3964</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9UUtr3DAQFqElCWl-QaHo2ItdPfzSoYVl0ySFhR6y0KOQpXF2tra1lbwbkl9fuZuG9FIQSMx8j9F8hLznLOeMV5-2ObToh1ww3uSszpkoTsi5kKXIpKqKN6_eZ-Qyxi1jjJdFKjan5EwyVlasYufk6QpsABPB0VvYWXQ40hUcoI90EYAuYvQWzZTaDzht6Mo_0LsJjHvM4pTKiTT4-963iZbOcoO9CzDSHzP4Du3PHugS-p5eYZxdZtDajE9mRPOOvO1MH-Hy-b4g6-uv6-Vttvp-8225WGW2KNWUuUYoYXlneGNqKzvFZcFNUzeFLEvHStFVnatl6zroWlW7koNsuWoUmJZLLi_Il6Psbt8O4CyMUzC93gUcTHjU3qD-tzPiRt_7g644r9LCksDHZ4Hgf-0hTnrAaNOnzAh-H7VgtVJpm1wkqDxCbfAxBuhebDjTc256q__kpufcNKt1yi2xPrye8IXzN6UE-HwEpFjggBB0tAijBYcB7KSdx_8a_AbgmKvQ</recordid><startdate>20180801</startdate><enddate>20180801</enddate><creator>Lee, Nathaniel</creator><creator>Makani, Julie</creator><creator>Tluway, Furahini</creator><creator>Makubi, Abel</creator><creator>Armitage, Andrew E.</creator><creator>Pasricha, Sant-Rayn</creator><creator>Drakesmith, Hal</creator><creator>Prentice, Andrew M.</creator><creator>Cox, Sharon E.</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20180801</creationdate><title>Decreased Hepcidin Levels Are Associated with Low Steady-state Hemoglobin in Children With Sickle Cell Disease in Tanzania</title><author>Lee, Nathaniel ; Makani, Julie ; Tluway, Furahini ; Makubi, Abel ; Armitage, Andrew E. ; Pasricha, Sant-Rayn ; Drakesmith, Hal ; Prentice, Andrew M. ; Cox, Sharon E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c459t-d8292c1fa18a7c3f91341a8784355d052f6fd73bdfefb97d51e3b1989eab1313</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adolescent</topic><topic>Anemia, Sickle Cell - blood</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Female</topic><topic>Hemoglobins - analysis</topic><topic>Hepcidin</topic><topic>Hepcidins - blood</topic><topic>Humans</topic><topic>Iron metabolism</topic><topic>Male</topic><topic>Nutrition</topic><topic>Research Paper</topic><topic>Severity of Illness Index</topic><topic>Sickle cell anemia</topic><topic>Sickle cell disease</topic><topic>Sub-Saharan Africa</topic><topic>Tanzania</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lee, Nathaniel</creatorcontrib><creatorcontrib>Makani, Julie</creatorcontrib><creatorcontrib>Tluway, Furahini</creatorcontrib><creatorcontrib>Makubi, Abel</creatorcontrib><creatorcontrib>Armitage, Andrew E.</creatorcontrib><creatorcontrib>Pasricha, Sant-Rayn</creatorcontrib><creatorcontrib>Drakesmith, Hal</creatorcontrib><creatorcontrib>Prentice, Andrew M.</creatorcontrib><creatorcontrib>Cox, Sharon E.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>EBioMedicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lee, Nathaniel</au><au>Makani, Julie</au><au>Tluway, Furahini</au><au>Makubi, Abel</au><au>Armitage, Andrew E.</au><au>Pasricha, Sant-Rayn</au><au>Drakesmith, Hal</au><au>Prentice, Andrew M.</au><au>Cox, Sharon E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Decreased Hepcidin Levels Are Associated with Low Steady-state Hemoglobin in Children With Sickle Cell Disease in Tanzania</atitle><jtitle>EBioMedicine</jtitle><addtitle>EBioMedicine</addtitle><date>2018-08-01</date><risdate>2018</risdate><volume>34</volume><spage>158</spage><epage>164</epage><pages>158-164</pages><issn>2352-3964</issn><eissn>2352-3964</eissn><abstract>The contribution of hepcidin as a regulator of iron metabolism & erythropoiesis on the severity of anemia in sickle cell disease (SCD) remains poorly characterized, especially in Sub-Saharan African populations. The aims of the study were to determine if hepcidin is associated with severity of steady-state anemia in SCD and to investigate factors associated with hepcidin and anemia in SCD.
Archived samples from 199 Tanzanian children, 56% boys aged 3–18 with laboratory-confirmed SCD were analysed based on recorded averaged steady-state hemoglobin (ASSH) quartiles (lowest vs. highest). Univariable and multivariable logistic regression was used to assess associations with ASSH quartiles.
In univariable analysis, hepcidin <5·5 ng/mL was associated with increased odds of being in the lowest ASSH quartile (OR 2·20; 95%CI 1·2–3·93) but which was limited to girls (OR 4·85, 95%CI 1·79–13·09, p = .046 for interaction). In multivariable analyses including either reticulocyte percentage or erythropoietin, lower hepcidin remained significantly associated with lowest ASSH quartile, although the hepcidin-sex interaction no longer reached statistical significance. No associations with ASSH quartile were observed for markers of inflammation, hemolysis or potential iron markers except for microcytosis, associated with higher ASSH, but which was confounded by reticulocyte percentage and alpha-thalassaemia status.
Hepcidin is lower in more severely anaemic children with SCD independent of inflammation or markers of erythropoiesis.
Funding sources include The Wellcome Trust (080025, 095009, 094780 &070114), MRC-UK (MC-A760-5QX00), NIHR Oxford Biomedical Research Centre, and the Bill and Melinda Gates Foundation (“Hepcidin and Iron in Global Health”, OPP1055865).
•Low hepcidin levels are associated with severe anemia independent of markers of erythropoiesis and inflammation.•Low serum ferritin is present in some children but is not associated with severe anemia.•Although iron markers remain difficult to interpret in sickle cell disease, hepcidin levels were mostly below levels that would be expected to inhibit iron absorption and recycling.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>30056060</pmid><doi>10.1016/j.ebiom.2018.07.024</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adolescent Anemia, Sickle Cell - blood Child Child, Preschool Female Hemoglobins - analysis Hepcidin Hepcidins - blood Humans Iron metabolism Male Nutrition Research Paper Severity of Illness Index Sickle cell anemia Sickle cell disease Sub-Saharan Africa Tanzania |
| title | Decreased Hepcidin Levels Are Associated with Low Steady-state Hemoglobin in Children With Sickle Cell Disease in Tanzania |
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