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Association of Systemic Lupus Erythematosus With Decreased Immunosuppressive Potential of the IgG Glycome
Objective Glycans attached to the Fc portion of IgG are important modulators of IgG effector functions. Interindividual differences in IgG glycome composition are large and they associate strongly with different inflammatory and autoimmune diseases. IKZF1, HLA–DQ2A/B, and BACH2 genetic loci that aff...
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| Published in: | Arthritis & rheumatology (Hoboken, N.J.) N.J.), 2015-11, Vol.67 (11), p.2978-2989 |
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| container_title | Arthritis & rheumatology (Hoboken, N.J.) |
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| creator | Vučković, Frano Krištić, Jasminka Gudelj, Ivan Teruel, Maria Keser, Toma Pezer, Marija Pučić‐Baković, Maja Štambuk, Jerko Trbojević‐Akmačić, Irena Barrios, Clara Pavić, Tamara Menni, Cristina Wang, Youxin Zhou, Yong Cui, Liufu Song, Haicheng Zeng, Qiang Guo, Xiuhua Pons‐Estel, Bernardo A. McKeigue, Paul Leslie Patrick, Alan Gornik, Olga Spector, Tim D. Harjaček, Miroslav Alarcon‐Riquelme, Marta Molokhia, Mariam Wang, Wei Lauc, Gordan |
| description | Objective
Glycans attached to the Fc portion of IgG are important modulators of IgG effector functions. Interindividual differences in IgG glycome composition are large and they associate strongly with different inflammatory and autoimmune diseases. IKZF1, HLA–DQ2A/B, and BACH2 genetic loci that affect IgG glycome composition show pleiotropy with systemic lupus erythematosus (SLE), indicating a potentially causative role of aberrant IgG glycosylation in SLE. We undertook this large multicenter case–control study to determine whether SLE is associated with altered IgG glycosylation.
Methods
Using ultra‐performance liquid chromatography analysis of released glycans, we analyzed the composition of the IgG glycome in 261 SLE patients and 247 matched controls of Latin American Mestizo origin (the discovery cohort) and in 2 independent replication cohorts of different ethnicity (108 SLE patients and 193 controls from Trinidad, and 106 SLE patients and 105 controls from China).
Results
Multiple statistically significant differences in IgG glycome composition were observed between patients and controls. The most significant changes included decreased galactosylation and sialylation of IgG (which regulate proinflammatory and antiinflammatory actions of IgG) as well as decreased core fucose and increased bisecting N‐acetylglucosamine (which affect antibody‐dependent cell‐mediated cytotoxicity).
Conclusion
The IgG glycome in SLE patients is significantly altered in a way that decreases immunosuppressive action of circulating immunoglobulins. The magnitude of observed changes is associated with the intensity of the disease, indicating that aberrant IgG glycome composition or changes in IgG glycosylation may be an important molecular mechanism in SLE. |
| doi_str_mv | 10.1002/art.39273 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4626261</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3848468651</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4433-4fea646734e489400300cc177fe721af43035668e5f7f13c7683c667a6d866ec3</originalsourceid><addsrcrecordid>eNp1kV1LHDEUhkNRqqgX_QMS8MZerOZrkpmbwmJ1XVhQWsXLkGbPuJGZyTTJKPPvzboqtmBuksN58nCSF6FvlJxQQtipCemEV0zxL2iXcSYnBSPF1tuZVnQHHcT4QPKqFJGk-Ip2mGSEyILtIjeN0VtnkvMd9jX-PcYErbN4MfRDxOdhTCtoTfIxV3curfBPsAFMhCWet-3Q5UbfB4jRPQK-9gm65EyzVuWLeH4_w7NmtL6FfbRdmybCweu-h24vzm_OLieLq9n8bLqYWCE4n4gajBRScQGirAQhnBBrqVI1KEZNLTjhhZQlFLWqKbdKltxKqYxcllKC5Xvox8bbD39aWNo8UDCN7oNrTRi1N07_2-ncSt_7Ry1k_hZJs-D4VRD83wFi0q2LFprGdOCHqKliJStUWVYZPfoPffBD6PLz1pQqFGEv1PcNZYOPMUD9Pgwlep2hzhnqlwwze_hx-nfyLbEMnG6AJ9fA-LlJT3_dbJTPluymgQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1727570289</pqid></control><display><type>article</type><title>Association of Systemic Lupus Erythematosus With Decreased Immunosuppressive Potential of the IgG Glycome</title><source>Wiley</source><creator>Vučković, Frano ; Krištić, Jasminka ; Gudelj, Ivan ; Teruel, Maria ; Keser, Toma ; Pezer, Marija ; Pučić‐Baković, Maja ; Štambuk, Jerko ; Trbojević‐Akmačić, Irena ; Barrios, Clara ; Pavić, Tamara ; Menni, Cristina ; Wang, Youxin ; Zhou, Yong ; Cui, Liufu ; Song, Haicheng ; Zeng, Qiang ; Guo, Xiuhua ; Pons‐Estel, Bernardo A. ; McKeigue, Paul ; Leslie Patrick, Alan ; Gornik, Olga ; Spector, Tim D. ; Harjaček, Miroslav ; Alarcon‐Riquelme, Marta ; Molokhia, Mariam ; Wang, Wei ; Lauc, Gordan</creator><creatorcontrib>Vučković, Frano ; Krištić, Jasminka ; Gudelj, Ivan ; Teruel, Maria ; Keser, Toma ; Pezer, Marija ; Pučić‐Baković, Maja ; Štambuk, Jerko ; Trbojević‐Akmačić, Irena ; Barrios, Clara ; Pavić, Tamara ; Menni, Cristina ; Wang, Youxin ; Zhou, Yong ; Cui, Liufu ; Song, Haicheng ; Zeng, Qiang ; Guo, Xiuhua ; Pons‐Estel, Bernardo A. ; McKeigue, Paul ; Leslie Patrick, Alan ; Gornik, Olga ; Spector, Tim D. ; Harjaček, Miroslav ; Alarcon‐Riquelme, Marta ; Molokhia, Mariam ; Wang, Wei ; Lauc, Gordan</creatorcontrib><description>Objective
Glycans attached to the Fc portion of IgG are important modulators of IgG effector functions. Interindividual differences in IgG glycome composition are large and they associate strongly with different inflammatory and autoimmune diseases. IKZF1, HLA–DQ2A/B, and BACH2 genetic loci that affect IgG glycome composition show pleiotropy with systemic lupus erythematosus (SLE), indicating a potentially causative role of aberrant IgG glycosylation in SLE. We undertook this large multicenter case–control study to determine whether SLE is associated with altered IgG glycosylation.
Methods
Using ultra‐performance liquid chromatography analysis of released glycans, we analyzed the composition of the IgG glycome in 261 SLE patients and 247 matched controls of Latin American Mestizo origin (the discovery cohort) and in 2 independent replication cohorts of different ethnicity (108 SLE patients and 193 controls from Trinidad, and 106 SLE patients and 105 controls from China).
Results
Multiple statistically significant differences in IgG glycome composition were observed between patients and controls. The most significant changes included decreased galactosylation and sialylation of IgG (which regulate proinflammatory and antiinflammatory actions of IgG) as well as decreased core fucose and increased bisecting N‐acetylglucosamine (which affect antibody‐dependent cell‐mediated cytotoxicity).
Conclusion
The IgG glycome in SLE patients is significantly altered in a way that decreases immunosuppressive action of circulating immunoglobulins. The magnitude of observed changes is associated with the intensity of the disease, indicating that aberrant IgG glycome composition or changes in IgG glycosylation may be an important molecular mechanism in SLE.</description><identifier>ISSN: 2326-5191</identifier><identifier>EISSN: 2326-5205</identifier><identifier>DOI: 10.1002/art.39273</identifier><identifier>PMID: 26200652</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Adolescent ; Adult ; Aged ; Autoimmune diseases ; Case-Control Studies ; Female ; Genetic Predisposition to Disease ; Humans ; Immunoglobulin G - genetics ; Immunoglobulin G - immunology ; Immunoglobulin G - metabolism ; Lupus ; Lupus Erythematosus, Systemic - genetics ; Lupus Erythematosus, Systemic - immunology ; Lupus Erythematosus, Systemic - metabolism ; Male ; Middle Aged ; Systemic Lupus Erythematosus ; Young Adult</subject><ispartof>Arthritis & rheumatology (Hoboken, N.J.), 2015-11, Vol.67 (11), p.2978-2989</ispartof><rights>2015 The Authors. Arthritis & Rheumatology is published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology.</rights><rights>2015, American College of Rheumatology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4433-4fea646734e489400300cc177fe721af43035668e5f7f13c7683c667a6d866ec3</citedby><cites>FETCH-LOGICAL-c4433-4fea646734e489400300cc177fe721af43035668e5f7f13c7683c667a6d866ec3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fart.39273$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fart.39273$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>230,315,786,790,891,27957,27958,50923,51032</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26200652$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Vučković, Frano</creatorcontrib><creatorcontrib>Krištić, Jasminka</creatorcontrib><creatorcontrib>Gudelj, Ivan</creatorcontrib><creatorcontrib>Teruel, Maria</creatorcontrib><creatorcontrib>Keser, Toma</creatorcontrib><creatorcontrib>Pezer, Marija</creatorcontrib><creatorcontrib>Pučić‐Baković, Maja</creatorcontrib><creatorcontrib>Štambuk, Jerko</creatorcontrib><creatorcontrib>Trbojević‐Akmačić, Irena</creatorcontrib><creatorcontrib>Barrios, Clara</creatorcontrib><creatorcontrib>Pavić, Tamara</creatorcontrib><creatorcontrib>Menni, Cristina</creatorcontrib><creatorcontrib>Wang, Youxin</creatorcontrib><creatorcontrib>Zhou, Yong</creatorcontrib><creatorcontrib>Cui, Liufu</creatorcontrib><creatorcontrib>Song, Haicheng</creatorcontrib><creatorcontrib>Zeng, Qiang</creatorcontrib><creatorcontrib>Guo, Xiuhua</creatorcontrib><creatorcontrib>Pons‐Estel, Bernardo A.</creatorcontrib><creatorcontrib>McKeigue, Paul</creatorcontrib><creatorcontrib>Leslie Patrick, Alan</creatorcontrib><creatorcontrib>Gornik, Olga</creatorcontrib><creatorcontrib>Spector, Tim D.</creatorcontrib><creatorcontrib>Harjaček, Miroslav</creatorcontrib><creatorcontrib>Alarcon‐Riquelme, Marta</creatorcontrib><creatorcontrib>Molokhia, Mariam</creatorcontrib><creatorcontrib>Wang, Wei</creatorcontrib><creatorcontrib>Lauc, Gordan</creatorcontrib><title>Association of Systemic Lupus Erythematosus With Decreased Immunosuppressive Potential of the IgG Glycome</title><title>Arthritis & rheumatology (Hoboken, N.J.)</title><addtitle>Arthritis Rheumatol</addtitle><description>Objective
Glycans attached to the Fc portion of IgG are important modulators of IgG effector functions. Interindividual differences in IgG glycome composition are large and they associate strongly with different inflammatory and autoimmune diseases. IKZF1, HLA–DQ2A/B, and BACH2 genetic loci that affect IgG glycome composition show pleiotropy with systemic lupus erythematosus (SLE), indicating a potentially causative role of aberrant IgG glycosylation in SLE. We undertook this large multicenter case–control study to determine whether SLE is associated with altered IgG glycosylation.
Methods
Using ultra‐performance liquid chromatography analysis of released glycans, we analyzed the composition of the IgG glycome in 261 SLE patients and 247 matched controls of Latin American Mestizo origin (the discovery cohort) and in 2 independent replication cohorts of different ethnicity (108 SLE patients and 193 controls from Trinidad, and 106 SLE patients and 105 controls from China).
Results
Multiple statistically significant differences in IgG glycome composition were observed between patients and controls. The most significant changes included decreased galactosylation and sialylation of IgG (which regulate proinflammatory and antiinflammatory actions of IgG) as well as decreased core fucose and increased bisecting N‐acetylglucosamine (which affect antibody‐dependent cell‐mediated cytotoxicity).
Conclusion
The IgG glycome in SLE patients is significantly altered in a way that decreases immunosuppressive action of circulating immunoglobulins. The magnitude of observed changes is associated with the intensity of the disease, indicating that aberrant IgG glycome composition or changes in IgG glycosylation may be an important molecular mechanism in SLE.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Autoimmune diseases</subject><subject>Case-Control Studies</subject><subject>Female</subject><subject>Genetic Predisposition to Disease</subject><subject>Humans</subject><subject>Immunoglobulin G - genetics</subject><subject>Immunoglobulin G - immunology</subject><subject>Immunoglobulin G - metabolism</subject><subject>Lupus</subject><subject>Lupus Erythematosus, Systemic - genetics</subject><subject>Lupus Erythematosus, Systemic - immunology</subject><subject>Lupus Erythematosus, Systemic - metabolism</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Systemic Lupus Erythematosus</subject><subject>Young Adult</subject><issn>2326-5191</issn><issn>2326-5205</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><recordid>eNp1kV1LHDEUhkNRqqgX_QMS8MZerOZrkpmbwmJ1XVhQWsXLkGbPuJGZyTTJKPPvzboqtmBuksN58nCSF6FvlJxQQtipCemEV0zxL2iXcSYnBSPF1tuZVnQHHcT4QPKqFJGk-Ip2mGSEyILtIjeN0VtnkvMd9jX-PcYErbN4MfRDxOdhTCtoTfIxV3curfBPsAFMhCWet-3Q5UbfB4jRPQK-9gm65EyzVuWLeH4_w7NmtL6FfbRdmybCweu-h24vzm_OLieLq9n8bLqYWCE4n4gajBRScQGirAQhnBBrqVI1KEZNLTjhhZQlFLWqKbdKltxKqYxcllKC5Xvox8bbD39aWNo8UDCN7oNrTRi1N07_2-ncSt_7Ry1k_hZJs-D4VRD83wFi0q2LFprGdOCHqKliJStUWVYZPfoPffBD6PLz1pQqFGEv1PcNZYOPMUD9Pgwlep2hzhnqlwwze_hx-nfyLbEMnG6AJ9fA-LlJT3_dbJTPluymgQ</recordid><startdate>201511</startdate><enddate>201511</enddate><creator>Vučković, Frano</creator><creator>Krištić, Jasminka</creator><creator>Gudelj, Ivan</creator><creator>Teruel, Maria</creator><creator>Keser, Toma</creator><creator>Pezer, Marija</creator><creator>Pučić‐Baković, Maja</creator><creator>Štambuk, Jerko</creator><creator>Trbojević‐Akmačić, Irena</creator><creator>Barrios, Clara</creator><creator>Pavić, Tamara</creator><creator>Menni, Cristina</creator><creator>Wang, Youxin</creator><creator>Zhou, Yong</creator><creator>Cui, Liufu</creator><creator>Song, Haicheng</creator><creator>Zeng, Qiang</creator><creator>Guo, Xiuhua</creator><creator>Pons‐Estel, Bernardo A.</creator><creator>McKeigue, Paul</creator><creator>Leslie Patrick, Alan</creator><creator>Gornik, Olga</creator><creator>Spector, Tim D.</creator><creator>Harjaček, Miroslav</creator><creator>Alarcon‐Riquelme, Marta</creator><creator>Molokhia, Mariam</creator><creator>Wang, Wei</creator><creator>Lauc, Gordan</creator><general>Wiley Subscription Services, Inc</general><general>John Wiley and Sons Inc</general><scope>24P</scope><scope>WIN</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>7QL</scope><scope>7QP</scope><scope>7T5</scope><scope>7TM</scope><scope>7U7</scope><scope>C1K</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>201511</creationdate><title>Association of Systemic Lupus Erythematosus With Decreased Immunosuppressive Potential of the IgG Glycome</title><author>Vučković, Frano ; Krištić, Jasminka ; Gudelj, Ivan ; Teruel, Maria ; Keser, Toma ; Pezer, Marija ; Pučić‐Baković, Maja ; Štambuk, Jerko ; Trbojević‐Akmačić, Irena ; Barrios, Clara ; Pavić, Tamara ; Menni, Cristina ; Wang, Youxin ; Zhou, Yong ; Cui, Liufu ; Song, Haicheng ; Zeng, Qiang ; Guo, Xiuhua ; Pons‐Estel, Bernardo A. ; McKeigue, Paul ; Leslie Patrick, Alan ; Gornik, Olga ; Spector, Tim D. ; Harjaček, Miroslav ; Alarcon‐Riquelme, Marta ; Molokhia, Mariam ; Wang, Wei ; Lauc, Gordan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4433-4fea646734e489400300cc177fe721af43035668e5f7f13c7683c667a6d866ec3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Autoimmune diseases</topic><topic>Case-Control Studies</topic><topic>Female</topic><topic>Genetic Predisposition to Disease</topic><topic>Humans</topic><topic>Immunoglobulin G - genetics</topic><topic>Immunoglobulin G - immunology</topic><topic>Immunoglobulin G - metabolism</topic><topic>Lupus</topic><topic>Lupus Erythematosus, Systemic - genetics</topic><topic>Lupus Erythematosus, Systemic - immunology</topic><topic>Lupus Erythematosus, Systemic - metabolism</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Systemic Lupus Erythematosus</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Vučković, Frano</creatorcontrib><creatorcontrib>Krištić, Jasminka</creatorcontrib><creatorcontrib>Gudelj, Ivan</creatorcontrib><creatorcontrib>Teruel, Maria</creatorcontrib><creatorcontrib>Keser, Toma</creatorcontrib><creatorcontrib>Pezer, Marija</creatorcontrib><creatorcontrib>Pučić‐Baković, Maja</creatorcontrib><creatorcontrib>Štambuk, Jerko</creatorcontrib><creatorcontrib>Trbojević‐Akmačić, Irena</creatorcontrib><creatorcontrib>Barrios, Clara</creatorcontrib><creatorcontrib>Pavić, Tamara</creatorcontrib><creatorcontrib>Menni, Cristina</creatorcontrib><creatorcontrib>Wang, Youxin</creatorcontrib><creatorcontrib>Zhou, Yong</creatorcontrib><creatorcontrib>Cui, Liufu</creatorcontrib><creatorcontrib>Song, Haicheng</creatorcontrib><creatorcontrib>Zeng, Qiang</creatorcontrib><creatorcontrib>Guo, Xiuhua</creatorcontrib><creatorcontrib>Pons‐Estel, Bernardo A.</creatorcontrib><creatorcontrib>McKeigue, Paul</creatorcontrib><creatorcontrib>Leslie Patrick, Alan</creatorcontrib><creatorcontrib>Gornik, Olga</creatorcontrib><creatorcontrib>Spector, Tim D.</creatorcontrib><creatorcontrib>Harjaček, Miroslav</creatorcontrib><creatorcontrib>Alarcon‐Riquelme, Marta</creatorcontrib><creatorcontrib>Molokhia, Mariam</creatorcontrib><creatorcontrib>Wang, Wei</creatorcontrib><creatorcontrib>Lauc, Gordan</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Wiley Online Library</collection><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>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Arthritis & rheumatology (Hoboken, N.J.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Vučković, Frano</au><au>Krištić, Jasminka</au><au>Gudelj, Ivan</au><au>Teruel, Maria</au><au>Keser, Toma</au><au>Pezer, Marija</au><au>Pučić‐Baković, Maja</au><au>Štambuk, Jerko</au><au>Trbojević‐Akmačić, Irena</au><au>Barrios, Clara</au><au>Pavić, Tamara</au><au>Menni, Cristina</au><au>Wang, Youxin</au><au>Zhou, Yong</au><au>Cui, Liufu</au><au>Song, Haicheng</au><au>Zeng, Qiang</au><au>Guo, Xiuhua</au><au>Pons‐Estel, Bernardo A.</au><au>McKeigue, Paul</au><au>Leslie Patrick, Alan</au><au>Gornik, Olga</au><au>Spector, Tim D.</au><au>Harjaček, Miroslav</au><au>Alarcon‐Riquelme, Marta</au><au>Molokhia, Mariam</au><au>Wang, Wei</au><au>Lauc, Gordan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Association of Systemic Lupus Erythematosus With Decreased Immunosuppressive Potential of the IgG Glycome</atitle><jtitle>Arthritis & rheumatology (Hoboken, N.J.)</jtitle><addtitle>Arthritis Rheumatol</addtitle><date>2015-11</date><risdate>2015</risdate><volume>67</volume><issue>11</issue><spage>2978</spage><epage>2989</epage><pages>2978-2989</pages><issn>2326-5191</issn><eissn>2326-5205</eissn><notes>Dr. Lauc is the founder and chief executive officer of Genos Ltd., a private research organization that specializes in high‐throughput glycomic analysis, and has several patents in this field.</notes><notes>Mr. Vučković and Ms Krištić contributed equally to this work.</notes><notes>Dr. Harjaček has received consulting fees, speaking fees, and/or honoraria from AbbVie, Pfizer, and Roche (less than $10,000).</notes><notes>The views expressed herein are those of the authors and are not necessarily those of the UK National Health Service (NHS), National Institute for Health Research (NIHR), or Department of Health.</notes><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>Objective
Glycans attached to the Fc portion of IgG are important modulators of IgG effector functions. Interindividual differences in IgG glycome composition are large and they associate strongly with different inflammatory and autoimmune diseases. IKZF1, HLA–DQ2A/B, and BACH2 genetic loci that affect IgG glycome composition show pleiotropy with systemic lupus erythematosus (SLE), indicating a potentially causative role of aberrant IgG glycosylation in SLE. We undertook this large multicenter case–control study to determine whether SLE is associated with altered IgG glycosylation.
Methods
Using ultra‐performance liquid chromatography analysis of released glycans, we analyzed the composition of the IgG glycome in 261 SLE patients and 247 matched controls of Latin American Mestizo origin (the discovery cohort) and in 2 independent replication cohorts of different ethnicity (108 SLE patients and 193 controls from Trinidad, and 106 SLE patients and 105 controls from China).
Results
Multiple statistically significant differences in IgG glycome composition were observed between patients and controls. The most significant changes included decreased galactosylation and sialylation of IgG (which regulate proinflammatory and antiinflammatory actions of IgG) as well as decreased core fucose and increased bisecting N‐acetylglucosamine (which affect antibody‐dependent cell‐mediated cytotoxicity).
Conclusion
The IgG glycome in SLE patients is significantly altered in a way that decreases immunosuppressive action of circulating immunoglobulins. The magnitude of observed changes is associated with the intensity of the disease, indicating that aberrant IgG glycome composition or changes in IgG glycosylation may be an important molecular mechanism in SLE.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>26200652</pmid><doi>10.1002/art.39273</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2326-5191 |
| ispartof | Arthritis & rheumatology (Hoboken, N.J.), 2015-11, Vol.67 (11), p.2978-2989 |
| issn | 2326-5191 2326-5205 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4626261 |
| source | Wiley |
| subjects | Adolescent Adult Aged Autoimmune diseases Case-Control Studies Female Genetic Predisposition to Disease Humans Immunoglobulin G - genetics Immunoglobulin G - immunology Immunoglobulin G - metabolism Lupus Lupus Erythematosus, Systemic - genetics Lupus Erythematosus, Systemic - immunology Lupus Erythematosus, Systemic - metabolism Male Middle Aged Systemic Lupus Erythematosus Young Adult |
| title | Association of Systemic Lupus Erythematosus With Decreased Immunosuppressive Potential of the IgG Glycome |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-09-23T04%3A27%3A33IST&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=Association%20of%20Systemic%20Lupus%20Erythematosus%20With%20Decreased%20Immunosuppressive%20Potential%20of%20the%20IgG%20Glycome&rft.jtitle=Arthritis%20&%20rheumatology%20(Hoboken,%20N.J.)&rft.au=Vu%C4%8Dkovi%C4%87,%20Frano&rft.date=2015-11&rft.volume=67&rft.issue=11&rft.spage=2978&rft.epage=2989&rft.pages=2978-2989&rft.issn=2326-5191&rft.eissn=2326-5205&rft_id=info:doi/10.1002/art.39273&rft_dat=%3Cproquest_pubme%3E3848468651%3C/proquest_pubme%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c4433-4fea646734e489400300cc177fe721af43035668e5f7f13c7683c667a6d866ec3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1727570289&rft_id=info:pmid/26200652&rfr_iscdi=true |