HCV infection in hemophilia A patients is associated with altered cytokines and chemokines profile and might modulate the levels of FVIII inhibitor
Prevalence of hepatitis C virus (HCV) is high in hemophilia A patients and the development of FVIII inhibitor is another challenge in the management of these individuals. The influence of HCV infection in the occurrence of inhibitors was investigated by the comparison of clinical and laboratory data...
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| Veröffentlicht in: | Journal of medical virology 2022-02, Vol.94 (2), p.683-691 |
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| creator | Bolina‐Santos, Eduarda Chaves, Daniel G. Silva‐Malta, Maria C. F. Carmo, Ricardo A. Barbosa‐Stancioli, Edel F. Lobato Martins, Marina |
| description | Prevalence of hepatitis C virus (HCV) is high in hemophilia A patients and the development of FVIII inhibitor is another challenge in the management of these individuals. The influence of HCV infection in the occurrence of inhibitors was investigated by the comparison of clinical and laboratory data from noninfected (NI, n = 96) and chronically HCV‐infected (HCV, n = 58) hemophilia A patients. Concentrations of plasmatic cytokines (IL‐2, IL‐4, IL‐6, IL‐10, TNF, IFN‐γ, and IL‐17A) and chemokines (CCL2, CCL5, CXCL8, CXCL9, and CXCL10) were quantified from patients' samples. The results showed that older age, use of cryoprecipitate and fresh frozen plasma, and severe hemophilia were associated with HCV infection, whereas exclusive use of virus inactivated clotting factors was a protector factor to acquiring HCV infection. HCV infection was strongly associated with low levels of inhibitor (OR = 20.53, p |
| doi_str_mv | 10.1002/jmv.27432 |
| format | Article |
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Highlights
HCV infection is strongly associated with low levels of FVIII inhibitors in hemophilia A patients.
Noninfected and chronically HCV infected hemophilia A patients, without or with history of inhibitory development have characteristic cytokines and chemokines profiles.
HCV infection might influence the natural course of hemophilia A by inducing an antiviral response that leads to low levels of FVIII inhibitors.</description><identifier>ISSN: 0146-6615</identifier><identifier>EISSN: 1096-9071</identifier><identifier>DOI: 10.1002/jmv.27432</identifier><identifier>PMID: 34738645</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Adolescent ; Adult ; Blood Coagulation Factor Inhibitors - therapeutic use ; Chemokines ; Chemokines - metabolism ; Clotting ; Coagulation factors ; CXCL10 protein ; Cytokines ; Cytokines - metabolism ; Factor VIII - antagonists & inhibitors ; Female ; HCV ; Hemophilia ; Hemophilia A - complications ; Hemophilia A - therapy ; Hepatitis C ; Hepatitis C, Chronic - complications ; Hepatitis C, Chronic - therapy ; Humans ; Infections ; Inflammation ; inhibitor ; Inhibitors ; Interferon ; Low concentrations ; Male ; Middle Aged ; Monocyte chemoattractant protein 1 ; Patients ; Plasma ; Tumor necrosis factor ; Virology ; Viruses ; Young Adult</subject><ispartof>Journal of medical virology, 2022-02, Vol.94 (2), p.683-691</ispartof><rights>2021 Wiley Periodicals LLC</rights><rights>2021 Wiley Periodicals LLC.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3532-c3442a6476dafe2b97edf799321b094fd1aaa8a901cd58a3d40c62392f4938343</citedby><cites>FETCH-LOGICAL-c3532-c3442a6476dafe2b97edf799321b094fd1aaa8a901cd58a3d40c62392f4938343</cites><orcidid>0000-0003-2506-8450</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjmv.27432$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjmv.27432$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34738645$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bolina‐Santos, Eduarda</creatorcontrib><creatorcontrib>Chaves, Daniel G.</creatorcontrib><creatorcontrib>Silva‐Malta, Maria C. F.</creatorcontrib><creatorcontrib>Carmo, Ricardo A.</creatorcontrib><creatorcontrib>Barbosa‐Stancioli, Edel F.</creatorcontrib><creatorcontrib>Lobato Martins, Marina</creatorcontrib><title>HCV infection in hemophilia A patients is associated with altered cytokines and chemokines profile and might modulate the levels of FVIII inhibitor</title><title>Journal of medical virology</title><addtitle>J Med Virol</addtitle><description>Prevalence of hepatitis C virus (HCV) is high in hemophilia A patients and the development of FVIII inhibitor is another challenge in the management of these individuals. The influence of HCV infection in the occurrence of inhibitors was investigated by the comparison of clinical and laboratory data from noninfected (NI, n = 96) and chronically HCV‐infected (HCV, n = 58) hemophilia A patients. Concentrations of plasmatic cytokines (IL‐2, IL‐4, IL‐6, IL‐10, TNF, IFN‐γ, and IL‐17A) and chemokines (CCL2, CCL5, CXCL8, CXCL9, and CXCL10) were quantified from patients' samples. The results showed that older age, use of cryoprecipitate and fresh frozen plasma, and severe hemophilia were associated with HCV infection, whereas exclusive use of virus inactivated clotting factors was a protector factor to acquiring HCV infection. HCV infection was strongly associated with low levels of inhibitor (OR = 20.53, p < 0.001). Patients with a history of inhibitor (INB+) presented a mixed immune profile characterized by higher levels of pro‐and anti‐inflammatory cytokines than those without a history of inhibitor (INB−). The highest levels of CCL2 and CXCL8 were seen in HCVINB−, whereas CXCL9 and CXCL10 in HCVINB+. Heatmap analysis of the set of cytokines and chemokines concentration distributed HCV patients into two distinct clusters, HCVINB+ and HCVINB‐, both characterized by low concentrations of IL‐4, while noninfected patients were grouped in a single block regardless of inhibitor development history (NIINB−/INB+). This finding suggests that the strong association between HCV infection and low levels of factor VIII inhibitors might be due to the modulation of the cytokine and chemokine network established by the antiviral response.
Highlights
HCV infection is strongly associated with low levels of FVIII inhibitors in hemophilia A patients.
Noninfected and chronically HCV infected hemophilia A patients, without or with history of inhibitory development have characteristic cytokines and chemokines profiles.
HCV infection might influence the natural course of hemophilia A by inducing an antiviral response that leads to low levels of FVIII inhibitors.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Blood Coagulation Factor Inhibitors - therapeutic use</subject><subject>Chemokines</subject><subject>Chemokines - metabolism</subject><subject>Clotting</subject><subject>Coagulation factors</subject><subject>CXCL10 protein</subject><subject>Cytokines</subject><subject>Cytokines - metabolism</subject><subject>Factor VIII - antagonists & inhibitors</subject><subject>Female</subject><subject>HCV</subject><subject>Hemophilia</subject><subject>Hemophilia A - complications</subject><subject>Hemophilia A - therapy</subject><subject>Hepatitis C</subject><subject>Hepatitis C, Chronic - complications</subject><subject>Hepatitis C, Chronic - therapy</subject><subject>Humans</subject><subject>Infections</subject><subject>Inflammation</subject><subject>inhibitor</subject><subject>Inhibitors</subject><subject>Interferon</subject><subject>Low concentrations</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Monocyte chemoattractant protein 1</subject><subject>Patients</subject><subject>Plasma</subject><subject>Tumor necrosis factor</subject><subject>Virology</subject><subject>Viruses</subject><subject>Young Adult</subject><issn>0146-6615</issn><issn>1096-9071</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kc1O3DAUhS1UVKa0C16gssSGLgb8FydeohGUqUBs6GwtT3JNPHXiIXZA8xx94XoIdFGpG9vH-u65V_cgdELJOSWEXWy653NWCs4O0IwSJeeKlPQDmhEq5FxKWhyhTzFuCCGVYuwjOuKi5JUUxQz9vlmssOst1MmFPr9wC13Yts47gy_x1iQHfYrYRWxiDLUzCRr84lKLjU8wZFHvUvjleshEn9W-fpLbIVjn4fW7c49twl1oRp8dcGoBe3gGH3Gw-Hq1XC5z79atXQrDZ3RojY_w5e0-Rj-vrx4WN_Pb--_LxeXtvOYFZ_kUghkpStkYC2ytSmhsqRRndE2UsA01xlRGEVo3RWV4I0gtGVfMCsUrLvgxOpt886BPI8SkOxdr8N70EMaoWaEEU5WURUZP_0E3YRz6PJ1mklSEcl7tqW8TVQ8hxgGs3g6uM8NOU6L3SemclH5NKrNf3xzHdQfNX_I9mgxcTMBL3uHu_076x91qsvwDq82eEQ</recordid><startdate>202202</startdate><enddate>202202</enddate><creator>Bolina‐Santos, Eduarda</creator><creator>Chaves, Daniel G.</creator><creator>Silva‐Malta, Maria C. F.</creator><creator>Carmo, Ricardo A.</creator><creator>Barbosa‐Stancioli, Edel F.</creator><creator>Lobato Martins, Marina</creator><general>Wiley Subscription Services, Inc</general><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>7QL</scope><scope>7TK</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-2506-8450</orcidid></search><sort><creationdate>202202</creationdate><title>HCV infection in hemophilia A patients is associated with altered cytokines and chemokines profile and might modulate the levels of FVIII inhibitor</title><author>Bolina‐Santos, Eduarda ; Chaves, Daniel G. ; Silva‐Malta, Maria C. 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F.</creatorcontrib><creatorcontrib>Carmo, Ricardo A.</creatorcontrib><creatorcontrib>Barbosa‐Stancioli, Edel F.</creatorcontrib><creatorcontrib>Lobato Martins, Marina</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of medical virology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bolina‐Santos, Eduarda</au><au>Chaves, Daniel G.</au><au>Silva‐Malta, Maria C. F.</au><au>Carmo, Ricardo A.</au><au>Barbosa‐Stancioli, Edel F.</au><au>Lobato Martins, Marina</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>HCV infection in hemophilia A patients is associated with altered cytokines and chemokines profile and might modulate the levels of FVIII inhibitor</atitle><jtitle>Journal of medical virology</jtitle><addtitle>J Med Virol</addtitle><date>2022-02</date><risdate>2022</risdate><volume>94</volume><issue>2</issue><spage>683</spage><epage>691</epage><pages>683-691</pages><issn>0146-6615</issn><eissn>1096-9071</eissn><abstract>Prevalence of hepatitis C virus (HCV) is high in hemophilia A patients and the development of FVIII inhibitor is another challenge in the management of these individuals. The influence of HCV infection in the occurrence of inhibitors was investigated by the comparison of clinical and laboratory data from noninfected (NI, n = 96) and chronically HCV‐infected (HCV, n = 58) hemophilia A patients. Concentrations of plasmatic cytokines (IL‐2, IL‐4, IL‐6, IL‐10, TNF, IFN‐γ, and IL‐17A) and chemokines (CCL2, CCL5, CXCL8, CXCL9, and CXCL10) were quantified from patients' samples. The results showed that older age, use of cryoprecipitate and fresh frozen plasma, and severe hemophilia were associated with HCV infection, whereas exclusive use of virus inactivated clotting factors was a protector factor to acquiring HCV infection. HCV infection was strongly associated with low levels of inhibitor (OR = 20.53, p < 0.001). Patients with a history of inhibitor (INB+) presented a mixed immune profile characterized by higher levels of pro‐and anti‐inflammatory cytokines than those without a history of inhibitor (INB−). The highest levels of CCL2 and CXCL8 were seen in HCVINB−, whereas CXCL9 and CXCL10 in HCVINB+. Heatmap analysis of the set of cytokines and chemokines concentration distributed HCV patients into two distinct clusters, HCVINB+ and HCVINB‐, both characterized by low concentrations of IL‐4, while noninfected patients were grouped in a single block regardless of inhibitor development history (NIINB−/INB+). This finding suggests that the strong association between HCV infection and low levels of factor VIII inhibitors might be due to the modulation of the cytokine and chemokine network established by the antiviral response.
Highlights
HCV infection is strongly associated with low levels of FVIII inhibitors in hemophilia A patients.
Noninfected and chronically HCV infected hemophilia A patients, without or with history of inhibitory development have characteristic cytokines and chemokines profiles.
HCV infection might influence the natural course of hemophilia A by inducing an antiviral response that leads to low levels of FVIII inhibitors.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>34738645</pmid><doi>10.1002/jmv.27432</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0003-2506-8450</orcidid></addata></record> |
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| subjects | Adolescent Adult Blood Coagulation Factor Inhibitors - therapeutic use Chemokines Chemokines - metabolism Clotting Coagulation factors CXCL10 protein Cytokines Cytokines - metabolism Factor VIII - antagonists & inhibitors Female HCV Hemophilia Hemophilia A - complications Hemophilia A - therapy Hepatitis C Hepatitis C, Chronic - complications Hepatitis C, Chronic - therapy Humans Infections Inflammation inhibitor Inhibitors Interferon Low concentrations Male Middle Aged Monocyte chemoattractant protein 1 Patients Plasma Tumor necrosis factor Virology Viruses Young Adult |
| title | HCV infection in hemophilia A patients is associated with altered cytokines and chemokines profile and might modulate the levels of FVIII inhibitor |
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