Fc Receptor Variants and Disease: A Crucial Factor to Consider in the Antibody Therapeutics in Clinic
The fragment crystallizable (Fc) domain of antibodies is responsible for their protective function and long-lasting serum half-life via Fc-mediated effector function, transcytosis, and recycling through its interaction with Fc receptors (FcRs) expressed on various immune leukocytes, epithelial, and...
Gespeichert in:
| Veröffentlicht in: | International journal of molecular sciences 2021-08, Vol.22 (17), p.9489 |
|---|---|
| Hauptverfasser: | , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | |
|---|---|
| container_issue | 17 |
| container_start_page | 9489 |
| container_title | International journal of molecular sciences |
| container_volume | 22 |
| creator | Kim, Jin Lee, Ji Young Kim, Han Gil Kwak, Min Woo Kang, Tae Hyun |
| description | The fragment crystallizable (Fc) domain of antibodies is responsible for their protective function and long-lasting serum half-life via Fc-mediated effector function, transcytosis, and recycling through its interaction with Fc receptors (FcRs) expressed on various immune leukocytes, epithelial, and endothelial cells. Therefore, the Fc-FcRs interaction is a control point of both endogenous and therapeutic antibody function. There are a number of reported genetic variants of FcRs, which include polymorphisms in (i) extracellular domain of FcRs, which change their affinities to Fc domain of antibodies; (ii) both cytoplasmic and intracellular domain, which alters the extent of signal transduction; and (iii) the promoter region of the FcRs gene, which affects the expression level of FcRs, thus being associated with the pathogenesis of disease indications. In this review, we firstly describe the correlation between the genetic variants of FcRs and immunological disorders by individual differences in the extent of FcRs-mediated regulations. Secondly, we discuss the influence of the genetic variants of FcRs on the susceptibility to infectious diseases or cancer in the perspective of FcRs-induced effector functions. Overall, we concluded that the genetic variants of FcRs are one of the key elements in the design of antibody therapeutics due to their variety of clinical outcomes among individuals. |
| doi_str_mv | 10.3390/ijms22179489 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8431278</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2571238795</sourcerecordid><originalsourceid>FETCH-LOGICAL-c412t-635dbe9b40c539cdc971448cda33e21accbb4e1ee37ae967e35faab55b0e77c13</originalsourceid><addsrcrecordid>eNpdkd1rFDEUxYMotlbffJaALz64Np-TiQ-FZXStUChI9TXcydx1s8wma5IR-t87a2vZ-nQPnB-HeziEvObsg5SWnYftrgjBjVWtfUJOuRJiwVhjnh7pE_KilC1jQgptn5MTqfSsbXtKcOXpN_S4rynTH5ADxFooxIF-CgWh4Ee6pF2efICRrsAfsJpol2IJA2YaIq0bpMtYQ5-GW3qzwQx7nGrw5WB2Y4jBvyTP1jAWfHV_z8j31eeb7nJxdf3la7e8WnjFRV00Ug892l4xr6X1g7eGK9X6AaREwcH7vlfIEaUBtI1BqdcAvdY9Q2M8l2fk4i53P_U7HDzGmmF0-xx2kG9dguAeOzFs3M_027VKcmHaOeDdfUBOvyYs1e1C8TiOEDFNxQltuBVtY5sZffsfuk1TjnO9v5SQrbF6pt7fUT6nUjKuH57hzB32c8f7zfib4wIP8L_B5B9ACJeK</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2571238795</pqid></control><display><type>article</type><title>Fc Receptor Variants and Disease: A Crucial Factor to Consider in the Antibody Therapeutics in Clinic</title><source>MDPI - Multidisciplinary Digital Publishing Institute</source><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><creator>Kim, Jin ; Lee, Ji Young ; Kim, Han Gil ; Kwak, Min Woo ; Kang, Tae Hyun</creator><creatorcontrib>Kim, Jin ; Lee, Ji Young ; Kim, Han Gil ; Kwak, Min Woo ; Kang, Tae Hyun</creatorcontrib><description>The fragment crystallizable (Fc) domain of antibodies is responsible for their protective function and long-lasting serum half-life via Fc-mediated effector function, transcytosis, and recycling through its interaction with Fc receptors (FcRs) expressed on various immune leukocytes, epithelial, and endothelial cells. Therefore, the Fc-FcRs interaction is a control point of both endogenous and therapeutic antibody function. There are a number of reported genetic variants of FcRs, which include polymorphisms in (i) extracellular domain of FcRs, which change their affinities to Fc domain of antibodies; (ii) both cytoplasmic and intracellular domain, which alters the extent of signal transduction; and (iii) the promoter region of the FcRs gene, which affects the expression level of FcRs, thus being associated with the pathogenesis of disease indications. In this review, we firstly describe the correlation between the genetic variants of FcRs and immunological disorders by individual differences in the extent of FcRs-mediated regulations. Secondly, we discuss the influence of the genetic variants of FcRs on the susceptibility to infectious diseases or cancer in the perspective of FcRs-induced effector functions. Overall, we concluded that the genetic variants of FcRs are one of the key elements in the design of antibody therapeutics due to their variety of clinical outcomes among individuals.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms22179489</identifier><identifier>PMID: 34502398</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Animals ; Antibodies ; Antibodies - therapeutic use ; Antigens ; Autoimmune diseases ; Autoimmune Diseases - immunology ; Communicable Diseases - immunology ; Cooperation ; Cytokines ; Cytotoxicity ; Domains ; Endothelial cells ; Fc receptors ; Gene expression ; Genetic diversity ; Genetic Variation - genetics ; Haplotypes ; Humans ; Immunoglobulin Fc Fragments - genetics ; Immunoglobulin Fc Fragments - metabolism ; Immunoglobulins ; Immunology ; Immunotherapy - methods ; Immunotherapy - trends ; Infectious diseases ; Leukocytes ; Neoplasms - therapy ; Pathogenesis ; Pathogens ; Receptor mechanisms ; Receptors, Fc - genetics ; Receptors, Fc - physiology ; Review ; Signal transduction</subject><ispartof>International journal of molecular sciences, 2021-08, Vol.22 (17), p.9489</ispartof><rights>2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2021 by the authors. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c412t-635dbe9b40c539cdc971448cda33e21accbb4e1ee37ae967e35faab55b0e77c13</citedby><cites>FETCH-LOGICAL-c412t-635dbe9b40c539cdc971448cda33e21accbb4e1ee37ae967e35faab55b0e77c13</cites><orcidid>0000-0002-7825-5877</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8431278/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8431278/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34502398$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kim, Jin</creatorcontrib><creatorcontrib>Lee, Ji Young</creatorcontrib><creatorcontrib>Kim, Han Gil</creatorcontrib><creatorcontrib>Kwak, Min Woo</creatorcontrib><creatorcontrib>Kang, Tae Hyun</creatorcontrib><title>Fc Receptor Variants and Disease: A Crucial Factor to Consider in the Antibody Therapeutics in Clinic</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>The fragment crystallizable (Fc) domain of antibodies is responsible for their protective function and long-lasting serum half-life via Fc-mediated effector function, transcytosis, and recycling through its interaction with Fc receptors (FcRs) expressed on various immune leukocytes, epithelial, and endothelial cells. Therefore, the Fc-FcRs interaction is a control point of both endogenous and therapeutic antibody function. There are a number of reported genetic variants of FcRs, which include polymorphisms in (i) extracellular domain of FcRs, which change their affinities to Fc domain of antibodies; (ii) both cytoplasmic and intracellular domain, which alters the extent of signal transduction; and (iii) the promoter region of the FcRs gene, which affects the expression level of FcRs, thus being associated with the pathogenesis of disease indications. In this review, we firstly describe the correlation between the genetic variants of FcRs and immunological disorders by individual differences in the extent of FcRs-mediated regulations. Secondly, we discuss the influence of the genetic variants of FcRs on the susceptibility to infectious diseases or cancer in the perspective of FcRs-induced effector functions. Overall, we concluded that the genetic variants of FcRs are one of the key elements in the design of antibody therapeutics due to their variety of clinical outcomes among individuals.</description><subject>Animals</subject><subject>Antibodies</subject><subject>Antibodies - therapeutic use</subject><subject>Antigens</subject><subject>Autoimmune diseases</subject><subject>Autoimmune Diseases - immunology</subject><subject>Communicable Diseases - immunology</subject><subject>Cooperation</subject><subject>Cytokines</subject><subject>Cytotoxicity</subject><subject>Domains</subject><subject>Endothelial cells</subject><subject>Fc receptors</subject><subject>Gene expression</subject><subject>Genetic diversity</subject><subject>Genetic Variation - genetics</subject><subject>Haplotypes</subject><subject>Humans</subject><subject>Immunoglobulin Fc Fragments - genetics</subject><subject>Immunoglobulin Fc Fragments - metabolism</subject><subject>Immunoglobulins</subject><subject>Immunology</subject><subject>Immunotherapy - methods</subject><subject>Immunotherapy - trends</subject><subject>Infectious diseases</subject><subject>Leukocytes</subject><subject>Neoplasms - therapy</subject><subject>Pathogenesis</subject><subject>Pathogens</subject><subject>Receptor mechanisms</subject><subject>Receptors, Fc - genetics</subject><subject>Receptors, Fc - physiology</subject><subject>Review</subject><subject>Signal transduction</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdkd1rFDEUxYMotlbffJaALz64Np-TiQ-FZXStUChI9TXcydx1s8wma5IR-t87a2vZ-nQPnB-HeziEvObsg5SWnYftrgjBjVWtfUJOuRJiwVhjnh7pE_KilC1jQgptn5MTqfSsbXtKcOXpN_S4rynTH5ADxFooxIF-CgWh4Ee6pF2efICRrsAfsJpol2IJA2YaIq0bpMtYQ5-GW3qzwQx7nGrw5WB2Y4jBvyTP1jAWfHV_z8j31eeb7nJxdf3la7e8WnjFRV00Ug892l4xr6X1g7eGK9X6AaREwcH7vlfIEaUBtI1BqdcAvdY9Q2M8l2fk4i53P_U7HDzGmmF0-xx2kG9dguAeOzFs3M_027VKcmHaOeDdfUBOvyYs1e1C8TiOEDFNxQltuBVtY5sZffsfuk1TjnO9v5SQrbF6pt7fUT6nUjKuH57hzB32c8f7zfib4wIP8L_B5B9ACJeK</recordid><startdate>20210831</startdate><enddate>20210831</enddate><creator>Kim, Jin</creator><creator>Lee, Ji Young</creator><creator>Kim, Han Gil</creator><creator>Kwak, Min Woo</creator><creator>Kang, Tae Hyun</creator><general>MDPI AG</general><general>MDPI</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-7825-5877</orcidid></search><sort><creationdate>20210831</creationdate><title>Fc Receptor Variants and Disease: A Crucial Factor to Consider in the Antibody Therapeutics in Clinic</title><author>Kim, Jin ; Lee, Ji Young ; Kim, Han Gil ; Kwak, Min Woo ; Kang, Tae Hyun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c412t-635dbe9b40c539cdc971448cda33e21accbb4e1ee37ae967e35faab55b0e77c13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Animals</topic><topic>Antibodies</topic><topic>Antibodies - therapeutic use</topic><topic>Antigens</topic><topic>Autoimmune diseases</topic><topic>Autoimmune Diseases - immunology</topic><topic>Communicable Diseases - immunology</topic><topic>Cooperation</topic><topic>Cytokines</topic><topic>Cytotoxicity</topic><topic>Domains</topic><topic>Endothelial cells</topic><topic>Fc receptors</topic><topic>Gene expression</topic><topic>Genetic diversity</topic><topic>Genetic Variation - genetics</topic><topic>Haplotypes</topic><topic>Humans</topic><topic>Immunoglobulin Fc Fragments - genetics</topic><topic>Immunoglobulin Fc Fragments - metabolism</topic><topic>Immunoglobulins</topic><topic>Immunology</topic><topic>Immunotherapy - methods</topic><topic>Immunotherapy - trends</topic><topic>Infectious diseases</topic><topic>Leukocytes</topic><topic>Neoplasms - therapy</topic><topic>Pathogenesis</topic><topic>Pathogens</topic><topic>Receptor mechanisms</topic><topic>Receptors, Fc - genetics</topic><topic>Receptors, Fc - physiology</topic><topic>Review</topic><topic>Signal transduction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kim, Jin</creatorcontrib><creatorcontrib>Lee, Ji Young</creatorcontrib><creatorcontrib>Kim, Han Gil</creatorcontrib><creatorcontrib>Kwak, Min Woo</creatorcontrib><creatorcontrib>Kang, Tae Hyun</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>International journal of molecular sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kim, Jin</au><au>Lee, Ji Young</au><au>Kim, Han Gil</au><au>Kwak, Min Woo</au><au>Kang, Tae Hyun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Fc Receptor Variants and Disease: A Crucial Factor to Consider in the Antibody Therapeutics in Clinic</atitle><jtitle>International journal of molecular sciences</jtitle><addtitle>Int J Mol Sci</addtitle><date>2021-08-31</date><risdate>2021</risdate><volume>22</volume><issue>17</issue><spage>9489</spage><pages>9489-</pages><issn>1422-0067</issn><issn>1661-6596</issn><eissn>1422-0067</eissn><abstract>The fragment crystallizable (Fc) domain of antibodies is responsible for their protective function and long-lasting serum half-life via Fc-mediated effector function, transcytosis, and recycling through its interaction with Fc receptors (FcRs) expressed on various immune leukocytes, epithelial, and endothelial cells. Therefore, the Fc-FcRs interaction is a control point of both endogenous and therapeutic antibody function. There are a number of reported genetic variants of FcRs, which include polymorphisms in (i) extracellular domain of FcRs, which change their affinities to Fc domain of antibodies; (ii) both cytoplasmic and intracellular domain, which alters the extent of signal transduction; and (iii) the promoter region of the FcRs gene, which affects the expression level of FcRs, thus being associated with the pathogenesis of disease indications. In this review, we firstly describe the correlation between the genetic variants of FcRs and immunological disorders by individual differences in the extent of FcRs-mediated regulations. Secondly, we discuss the influence of the genetic variants of FcRs on the susceptibility to infectious diseases or cancer in the perspective of FcRs-induced effector functions. Overall, we concluded that the genetic variants of FcRs are one of the key elements in the design of antibody therapeutics due to their variety of clinical outcomes among individuals.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>34502398</pmid><doi>10.3390/ijms22179489</doi><orcidid>https://orcid.org/0000-0002-7825-5877</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1422-0067 |
| ispartof | International journal of molecular sciences, 2021-08, Vol.22 (17), p.9489 |
| issn | 1422-0067 1661-6596 1422-0067 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8431278 |
| source | MDPI - Multidisciplinary Digital Publishing Institute; MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Animals Antibodies Antibodies - therapeutic use Antigens Autoimmune diseases Autoimmune Diseases - immunology Communicable Diseases - immunology Cooperation Cytokines Cytotoxicity Domains Endothelial cells Fc receptors Gene expression Genetic diversity Genetic Variation - genetics Haplotypes Humans Immunoglobulin Fc Fragments - genetics Immunoglobulin Fc Fragments - metabolism Immunoglobulins Immunology Immunotherapy - methods Immunotherapy - trends Infectious diseases Leukocytes Neoplasms - therapy Pathogenesis Pathogens Receptor mechanisms Receptors, Fc - genetics Receptors, Fc - physiology Review Signal transduction |
| title | Fc Receptor Variants and Disease: A Crucial Factor to Consider in the Antibody Therapeutics in Clinic |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-03T14%3A04%3A01IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Fc%20Receptor%20Variants%20and%20Disease:%20A%20Crucial%20Factor%20to%20Consider%20in%20the%20Antibody%20Therapeutics%20in%20Clinic&rft.jtitle=International%20journal%20of%20molecular%20sciences&rft.au=Kim,%20Jin&rft.date=2021-08-31&rft.volume=22&rft.issue=17&rft.spage=9489&rft.pages=9489-&rft.issn=1422-0067&rft.eissn=1422-0067&rft_id=info:doi/10.3390/ijms22179489&rft_dat=%3Cproquest_pubme%3E2571238795%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2571238795&rft_id=info:pmid/34502398&rfr_iscdi=true |