Heterogeneity of autoimmune diseases: pathophysiologic insights from genetics and implications for new therapies
Recent advances in genetics have deepened our understanding of the pathogenic mechanisms behind autoimmune and immune-mediated diseases. This has revealed both shared pathways and a considerable degree of heterogeneity between diseases. Recent advances in genome-wide association studies (GWAS) acros...
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| Veröffentlicht in: | Nature medicine 2015-07, Vol.21 (7), p.730-738 |
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| creator | Cho, Judy H Feldman, Marc |
| description | Recent advances in genetics have deepened our understanding of the pathogenic mechanisms behind autoimmune and immune-mediated diseases. This has revealed both shared pathways and a considerable degree of heterogeneity between diseases.
Recent advances in genome-wide association studies (GWAS) across autoimmune and immune-mediated diseases have augmented our understanding of pathogenic mechanisms underlying these diseases. This has further highlighted their heterogeneous nature, both within and between diseases. Furthermore, varying responses to therapy have also served to underline the importance of this heterogeneity in the manner in which these diseases are diagnosed and treated. Here we discuss our current understanding of the shared pathways of autoimmunity, including the tumor necrosis factor (TNF), major histocompatibility complex (MHC), interleukin 23 receptor (IL23R) and protein tyrosine phosphatase non-receptor type 22 (PTPN22) pathways. In addition, we summarize effective specific therapies tested across major autoimmune diseases, highlighting the insight they have provided into disease mechanisms and their implications for potential future improvements. |
| doi_str_mv | 10.1038/nm.3897 |
| format | Article |
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Recent advances in genome-wide association studies (GWAS) across autoimmune and immune-mediated diseases have augmented our understanding of pathogenic mechanisms underlying these diseases. This has further highlighted their heterogeneous nature, both within and between diseases. Furthermore, varying responses to therapy have also served to underline the importance of this heterogeneity in the manner in which these diseases are diagnosed and treated. Here we discuss our current understanding of the shared pathways of autoimmunity, including the tumor necrosis factor (TNF), major histocompatibility complex (MHC), interleukin 23 receptor (IL23R) and protein tyrosine phosphatase non-receptor type 22 (PTPN22) pathways. In addition, we summarize effective specific therapies tested across major autoimmune diseases, highlighting the insight they have provided into disease mechanisms and their implications for potential future improvements.</description><identifier>ISSN: 1078-8956</identifier><identifier>EISSN: 1546-170X</identifier><identifier>DOI: 10.1038/nm.3897</identifier><identifier>PMID: 26121193</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>631/208/248 ; 631/250/38 ; Animals ; Autoimmune diseases ; Autoimmune Diseases - genetics ; Autoimmune Diseases - immunology ; Autoimmune Diseases - physiopathology ; Autoimmune Diseases - therapy ; Biomedicine ; Cancer Research ; Care and treatment ; Cytokines ; Development and progression ; Genetic aspects ; Genetic Heterogeneity ; Genetics ; Genomes ; Heterogeneity ; Humans ; Infectious Diseases ; Lymphocyte Activation - immunology ; Metabolic Diseases ; Molecular Medicine ; Molecular Targeted Therapy ; Neurosciences ; Phenotype ; Physiological aspects ; review-article ; Signal Transduction ; Studies ; Tumor necrosis factor</subject><ispartof>Nature medicine, 2015-07, Vol.21 (7), p.730-738</ispartof><rights>Springer Nature America, Inc. 2015</rights><rights>COPYRIGHT 2015 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Jul 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c803t-464016594ce2941580fc57829d8de0ba8c0a7db7dba06382c1af84ee281ac0243</citedby><cites>FETCH-LOGICAL-c803t-464016594ce2941580fc57829d8de0ba8c0a7db7dba06382c1af84ee281ac0243</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/nm.3897$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/nm.3897$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,778,782,883,27907,27908,41471,42540,51302</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26121193$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cho, Judy H</creatorcontrib><creatorcontrib>Feldman, Marc</creatorcontrib><title>Heterogeneity of autoimmune diseases: pathophysiologic insights from genetics and implications for new therapies</title><title>Nature medicine</title><addtitle>Nat Med</addtitle><addtitle>Nat Med</addtitle><description>Recent advances in genetics have deepened our understanding of the pathogenic mechanisms behind autoimmune and immune-mediated diseases. This has revealed both shared pathways and a considerable degree of heterogeneity between diseases.
Recent advances in genome-wide association studies (GWAS) across autoimmune and immune-mediated diseases have augmented our understanding of pathogenic mechanisms underlying these diseases. This has further highlighted their heterogeneous nature, both within and between diseases. Furthermore, varying responses to therapy have also served to underline the importance of this heterogeneity in the manner in which these diseases are diagnosed and treated. Here we discuss our current understanding of the shared pathways of autoimmunity, including the tumor necrosis factor (TNF), major histocompatibility complex (MHC), interleukin 23 receptor (IL23R) and protein tyrosine phosphatase non-receptor type 22 (PTPN22) pathways. In addition, we summarize effective specific therapies tested across major autoimmune diseases, highlighting the insight they have provided into disease mechanisms and their implications for potential future improvements.</description><subject>631/208/248</subject><subject>631/250/38</subject><subject>Animals</subject><subject>Autoimmune diseases</subject><subject>Autoimmune Diseases - genetics</subject><subject>Autoimmune Diseases - immunology</subject><subject>Autoimmune Diseases - physiopathology</subject><subject>Autoimmune Diseases - therapy</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Care and treatment</subject><subject>Cytokines</subject><subject>Development and progression</subject><subject>Genetic aspects</subject><subject>Genetic Heterogeneity</subject><subject>Genetics</subject><subject>Genomes</subject><subject>Heterogeneity</subject><subject>Humans</subject><subject>Infectious Diseases</subject><subject>Lymphocyte Activation - immunology</subject><subject>Metabolic Diseases</subject><subject>Molecular Medicine</subject><subject>Molecular Targeted Therapy</subject><subject>Neurosciences</subject><subject>Phenotype</subject><subject>Physiological aspects</subject><subject>review-article</subject><subject>Signal Transduction</subject><subject>Studies</subject><subject>Tumor necrosis factor</subject><issn>1078-8956</issn><issn>1546-170X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqNkm1r1TAUx4sobk7xG0hA8OFFZ5K2aeILYQx1g8HAJ3wXctPTNqNNuiRV77c3dXO7d1xQEkjI-Z0_5-R_suwpwYcEF_yNHQ8LLup72T6pSpaTGn-_n-645jkXFdvLHoVwgTEucCUeZnuUEUqIKPaz6QQieNeBBRPXyLVIzdGZcZwtoMYEUAHCWzSp2LupXwfjBtcZjYwNputjQK13I1rSo9EBKdsgM06D0SoaZ1PYeWThJ4o9eDUZCI-zB60aAjy5Pg-yrx_efzk-yc_OP54eH53lmuMi5iUrMWGVKDVQUZKK41ZXNaei4Q3gleIaq7pZpa0wKzjVRLW8BKCcKI1pWRxk7650p3k1QqPBRq8GOXkzKr-WThm5HbGml537IauasKKkSeDVtYB3lzOEKEcTNAyDsuDmIElNa8YZFfW_USYqUldYLGU9v4NeuNnb9BMLVVYFT-3cUp0aQBrbulSiXkTlUUmJwKIQLFH5DmrxIvXjLLQmPW_xhzv4tBoYjd6Z8HorITERfsVOzSHI08-f_p89_7bNvthge1BD7IMb5j8jsw2-vAK1dyF4aG_8I1gugy_tKJfBT-SzTbtvuL-TfutRSCHbgd_4-DtavwH4UAk4</recordid><startdate>20150701</startdate><enddate>20150701</enddate><creator>Cho, Judy H</creator><creator>Feldman, Marc</creator><general>Nature Publishing Group US</general><general>Nature Publishing Group</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U7</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M2P</scope><scope>M7N</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20150701</creationdate><title>Heterogeneity of autoimmune diseases: pathophysiologic insights from genetics and implications for new therapies</title><author>Cho, Judy H ; Feldman, Marc</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c803t-464016594ce2941580fc57829d8de0ba8c0a7db7dba06382c1af84ee281ac0243</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>631/208/248</topic><topic>631/250/38</topic><topic>Animals</topic><topic>Autoimmune diseases</topic><topic>Autoimmune Diseases - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Nature medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cho, Judy H</au><au>Feldman, Marc</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Heterogeneity of autoimmune diseases: pathophysiologic insights from genetics and implications for new therapies</atitle><jtitle>Nature medicine</jtitle><stitle>Nat Med</stitle><addtitle>Nat Med</addtitle><date>2015-07-01</date><risdate>2015</risdate><volume>21</volume><issue>7</issue><spage>730</spage><epage>738</epage><pages>730-738</pages><issn>1078-8956</issn><eissn>1546-170X</eissn><abstract>Recent advances in genetics have deepened our understanding of the pathogenic mechanisms behind autoimmune and immune-mediated diseases. This has revealed both shared pathways and a considerable degree of heterogeneity between diseases.
Recent advances in genome-wide association studies (GWAS) across autoimmune and immune-mediated diseases have augmented our understanding of pathogenic mechanisms underlying these diseases. This has further highlighted their heterogeneous nature, both within and between diseases. Furthermore, varying responses to therapy have also served to underline the importance of this heterogeneity in the manner in which these diseases are diagnosed and treated. Here we discuss our current understanding of the shared pathways of autoimmunity, including the tumor necrosis factor (TNF), major histocompatibility complex (MHC), interleukin 23 receptor (IL23R) and protein tyrosine phosphatase non-receptor type 22 (PTPN22) pathways. In addition, we summarize effective specific therapies tested across major autoimmune diseases, highlighting the insight they have provided into disease mechanisms and their implications for potential future improvements.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>26121193</pmid><doi>10.1038/nm.3897</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Nature medicine, 2015-07, Vol.21 (7), p.730-738 |
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| source | MEDLINE; Nature Journals Online; SpringerLink Journals - AutoHoldings |
| subjects | 631/208/248 631/250/38 Animals Autoimmune diseases Autoimmune Diseases - genetics Autoimmune Diseases - immunology Autoimmune Diseases - physiopathology Autoimmune Diseases - therapy Biomedicine Cancer Research Care and treatment Cytokines Development and progression Genetic aspects Genetic Heterogeneity Genetics Genomes Heterogeneity Humans Infectious Diseases Lymphocyte Activation - immunology Metabolic Diseases Molecular Medicine Molecular Targeted Therapy Neurosciences Phenotype Physiological aspects review-article Signal Transduction Studies Tumor necrosis factor |
| title | Heterogeneity of autoimmune diseases: pathophysiologic insights from genetics and implications for new therapies |
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