Brief Report: Anti–RNPC‐3 Antibodies As a Marker of Cancer‐Associated Scleroderma

Objective Prior studies have demonstrated an increased risk of cancer‐associated scleroderma in patients with anti–RNA polymerase III (anti–RNAP III) autoantibodies as well as in patients who are triple‐negative for anticentromere (anti‐CENP), anti–topoisomerase I (anti–topo I), and anti–RNAP III (a...

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Veröffentlicht in:Arthritis & rheumatology (Hoboken, N.J.) N.J.), 2017-06, Vol.69 (6), p.1306-1312
Hauptverfasser: Shah, Ami A., Xu, George, Rosen, Antony, Hummers, Laura K., Wigley, Fredrick M., Elledge, Stephen J., Casciola‐Rosen, Livia
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container_issue 6
container_start_page 1306
container_title Arthritis & rheumatology (Hoboken, N.J.)
container_volume 69
creator Shah, Ami A.
Xu, George
Rosen, Antony
Hummers, Laura K.
Wigley, Fredrick M.
Elledge, Stephen J.
Casciola‐Rosen, Livia
description Objective Prior studies have demonstrated an increased risk of cancer‐associated scleroderma in patients with anti–RNA polymerase III (anti–RNAP III) autoantibodies as well as in patients who are triple‐negative for anticentromere (anti‐CENP), anti–topoisomerase I (anti–topo I), and anti–RNAP III (also known as anti‐POL) autoantibodies (referred to as CTP negative). In a recent study of 16 CTP‐negative scleroderma patients with coincident cancer, 25% of the patients were found to have autoantibodies to RNPC‐3, a member of the minor spliceosome complex. This investigation was undertaken to validate the relationship between anti–RNPC‐3 antibodies and cancer and examine the associated clinical phenotype in a large sample of scleroderma patients. Methods Scleroderma patients with cancer were assayed for anti‐CENP, anti–topo I, anti–RNAP III, and anti–RNPC‐3 autoantibodies. Disease characteristics and the cancer–scleroderma interval were compared across autoantibody groups. The relationship between autoantibody status and cancer‐associated scleroderma was assessed by logistic regression. Results Of 318 patients with scleroderma and cancer, 70 (22.0%) were positive for anti–RNAP III, 54 (17.0%) were positive for anti–topo I, and 96 (30.2%) were positive for anti‐CENP. Twelve patients (3.8% of the overall group or 12.2% of CTP‐negative patients) were positive for anti–RNPC‐3. Patients with anti–RNPC‐3 had a short cancer–scleroderma interval (median 0.9 years). Relative to patients with anti‐CENP, patients with anti–RNPC‐3 and those with anti–RNAP III had a >4‐fold increased risk of cancer within 2 years of scleroderma onset (for anti–RNPC‐3–positive patients, odds ratio [OR] 4.3, 95% confidence interval [95% CI] 1.10–16.9 [P = 0.037]; for anti–RNAP III–positive patients, OR 4.49, 95% CI 1.98–10.2 [P 
doi_str_mv 10.1002/art.40065
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In a recent study of 16 CTP‐negative scleroderma patients with coincident cancer, 25% of the patients were found to have autoantibodies to RNPC‐3, a member of the minor spliceosome complex. This investigation was undertaken to validate the relationship between anti–RNPC‐3 antibodies and cancer and examine the associated clinical phenotype in a large sample of scleroderma patients. Methods Scleroderma patients with cancer were assayed for anti‐CENP, anti–topo I, anti–RNAP III, and anti–RNPC‐3 autoantibodies. Disease characteristics and the cancer–scleroderma interval were compared across autoantibody groups. The relationship between autoantibody status and cancer‐associated scleroderma was assessed by logistic regression. Results Of 318 patients with scleroderma and cancer, 70 (22.0%) were positive for anti–RNAP III, 54 (17.0%) were positive for anti–topo I, and 96 (30.2%) were positive for anti‐CENP. Twelve patients (3.8% of the overall group or 12.2% of CTP‐negative patients) were positive for anti–RNPC‐3. Patients with anti–RNPC‐3 had a short cancer–scleroderma interval (median 0.9 years). Relative to patients with anti‐CENP, patients with anti–RNPC‐3 and those with anti–RNAP III had a &gt;4‐fold increased risk of cancer within 2 years of scleroderma onset (for anti–RNPC‐3–positive patients, odds ratio [OR] 4.3, 95% confidence interval [95% CI] 1.10–16.9 [P = 0.037]; for anti–RNAP III–positive patients, OR 4.49, 95% CI 1.98–10.2 [P &lt; 0.001]). Patients with anti–RNPC‐3 had severe restrictive lung disease, gastrointestinal disease, Raynaud's phenomenon, and myopathy. Conclusion Anti–RNPC‐3 autoantibodies, similar to anti–RNAP III autoantibodies, are associated with an increased risk of cancer at the onset of scleroderma. These data suggest the possibility of cancer‐induced autoimmunity in this subset of patients with scleroderma.</description><identifier>ISSN: 2326-5191</identifier><identifier>EISSN: 2326-5205</identifier><identifier>DOI: 10.1002/art.40065</identifier><identifier>PMID: 28217959</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Adult ; Antibodies ; Autoantibodies ; Autoantibodies - blood ; Autoantibodies - immunology ; Autoimmunity ; Biomarkers - blood ; Cancer ; Confidence intervals ; DNA topoisomerase ; DNA-directed RNA polymerase ; Female ; Health risk assessment ; Health risks ; Humans ; Logistic Models ; Lung diseases ; Male ; Middle Aged ; Myopathy ; Neoplasms - blood ; Neoplasms - complications ; Neoplasms - immunology ; Nuclear Proteins - immunology ; Patients ; Ribonucleic acid ; Risk ; RNA ; RNA polymerase ; RNA-Binding Proteins - immunology ; Scleroderma ; Scleroderma, Systemic - blood ; Scleroderma, Systemic - immunology</subject><ispartof>Arthritis &amp; rheumatology (Hoboken, N.J.), 2017-06, Vol.69 (6), p.1306-1312</ispartof><rights>2017, American College of Rheumatology</rights><rights>2017, American College of Rheumatology.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3695-a16ca9092be65c861fec0484851a64a566e068faece14cd6200787e292778a443</citedby><cites>FETCH-LOGICAL-c3695-a16ca9092be65c861fec0484851a64a566e068faece14cd6200787e292778a443</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.40065$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fart.40065$$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/28217959$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shah, Ami A.</creatorcontrib><creatorcontrib>Xu, George</creatorcontrib><creatorcontrib>Rosen, Antony</creatorcontrib><creatorcontrib>Hummers, Laura K.</creatorcontrib><creatorcontrib>Wigley, Fredrick M.</creatorcontrib><creatorcontrib>Elledge, Stephen J.</creatorcontrib><creatorcontrib>Casciola‐Rosen, Livia</creatorcontrib><title>Brief Report: Anti–RNPC‐3 Antibodies As a Marker of Cancer‐Associated Scleroderma</title><title>Arthritis &amp; rheumatology (Hoboken, N.J.)</title><addtitle>Arthritis Rheumatol</addtitle><description>Objective Prior studies have demonstrated an increased risk of cancer‐associated scleroderma in patients with anti–RNA polymerase III (anti–RNAP III) autoantibodies as well as in patients who are triple‐negative for anticentromere (anti‐CENP), anti–topoisomerase I (anti–topo I), and anti–RNAP III (also known as anti‐POL) autoantibodies (referred to as CTP negative). In a recent study of 16 CTP‐negative scleroderma patients with coincident cancer, 25% of the patients were found to have autoantibodies to RNPC‐3, a member of the minor spliceosome complex. This investigation was undertaken to validate the relationship between anti–RNPC‐3 antibodies and cancer and examine the associated clinical phenotype in a large sample of scleroderma patients. Methods Scleroderma patients with cancer were assayed for anti‐CENP, anti–topo I, anti–RNAP III, and anti–RNPC‐3 autoantibodies. Disease characteristics and the cancer–scleroderma interval were compared across autoantibody groups. The relationship between autoantibody status and cancer‐associated scleroderma was assessed by logistic regression. Results Of 318 patients with scleroderma and cancer, 70 (22.0%) were positive for anti–RNAP III, 54 (17.0%) were positive for anti–topo I, and 96 (30.2%) were positive for anti‐CENP. Twelve patients (3.8% of the overall group or 12.2% of CTP‐negative patients) were positive for anti–RNPC‐3. Patients with anti–RNPC‐3 had a short cancer–scleroderma interval (median 0.9 years). Relative to patients with anti‐CENP, patients with anti–RNPC‐3 and those with anti–RNAP III had a &gt;4‐fold increased risk of cancer within 2 years of scleroderma onset (for anti–RNPC‐3–positive patients, odds ratio [OR] 4.3, 95% confidence interval [95% CI] 1.10–16.9 [P = 0.037]; for anti–RNAP III–positive patients, OR 4.49, 95% CI 1.98–10.2 [P &lt; 0.001]). Patients with anti–RNPC‐3 had severe restrictive lung disease, gastrointestinal disease, Raynaud's phenomenon, and myopathy. Conclusion Anti–RNPC‐3 autoantibodies, similar to anti–RNAP III autoantibodies, are associated with an increased risk of cancer at the onset of scleroderma. These data suggest the possibility of cancer‐induced autoimmunity in this subset of patients with scleroderma.</description><subject>Adult</subject><subject>Antibodies</subject><subject>Autoantibodies</subject><subject>Autoantibodies - blood</subject><subject>Autoantibodies - immunology</subject><subject>Autoimmunity</subject><subject>Biomarkers - blood</subject><subject>Cancer</subject><subject>Confidence intervals</subject><subject>DNA topoisomerase</subject><subject>DNA-directed RNA polymerase</subject><subject>Female</subject><subject>Health risk assessment</subject><subject>Health risks</subject><subject>Humans</subject><subject>Logistic Models</subject><subject>Lung diseases</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Myopathy</subject><subject>Neoplasms - blood</subject><subject>Neoplasms - complications</subject><subject>Neoplasms - immunology</subject><subject>Nuclear Proteins - immunology</subject><subject>Patients</subject><subject>Ribonucleic acid</subject><subject>Risk</subject><subject>RNA</subject><subject>RNA polymerase</subject><subject>RNA-Binding Proteins - immunology</subject><subject>Scleroderma</subject><subject>Scleroderma, Systemic - blood</subject><subject>Scleroderma, Systemic - immunology</subject><issn>2326-5191</issn><issn>2326-5205</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp10MtKAzEUBuAgii3VhS8gA2500TaXSWbibizeoF6oFZchzZyB0WlTkynSXR9B8A37JMZeXAhmkwQ-fs75EToiuEMwpl3t6k6MseA7qEkZFW1OMd_dvokkDXTo_SsORyZYYL6PGjSlJJFcNtHLhSuhiAYwta4-j7JJXS4XX4P7x95y8clW_5HNS_BR5iMd3Wn3Bi6yRdTTEwMuoMx7a0pdQx49mQqczcGN9QHaK3Tl4XBzt9Dz1eWwd9PuP1zf9rJ-2zAheVsTYbTEko5AcJMKUoDBcRqnnGgRay4EYJEWGgyQ2OSCYpykCVBJkyTVccxa6HSdO3X2fQa-VuPSG6gqPQE784qkYeeYMUYDPflDX-3MTcJ0ikjMGGdEkKDO1so4672DQk1dOdZurghWP4WrULhaFR7s8SZxNhpD_iu39QbQXYOPsoL5_0kqGwzXkd_s8olT</recordid><startdate>201706</startdate><enddate>201706</enddate><creator>Shah, Ami A.</creator><creator>Xu, George</creator><creator>Rosen, Antony</creator><creator>Hummers, Laura K.</creator><creator>Wigley, Fredrick M.</creator><creator>Elledge, Stephen J.</creator><creator>Casciola‐Rosen, Livia</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>7QP</scope><scope>7T5</scope><scope>7TM</scope><scope>7U7</scope><scope>C1K</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope></search><sort><creationdate>201706</creationdate><title>Brief Report: Anti–RNPC‐3 Antibodies As a Marker of Cancer‐Associated Scleroderma</title><author>Shah, Ami A. ; Xu, George ; Rosen, Antony ; Hummers, Laura K. ; Wigley, Fredrick M. ; Elledge, Stephen J. ; Casciola‐Rosen, Livia</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3695-a16ca9092be65c861fec0484851a64a566e068faece14cd6200787e292778a443</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adult</topic><topic>Antibodies</topic><topic>Autoantibodies</topic><topic>Autoantibodies - blood</topic><topic>Autoantibodies - immunology</topic><topic>Autoimmunity</topic><topic>Biomarkers - blood</topic><topic>Cancer</topic><topic>Confidence intervals</topic><topic>DNA topoisomerase</topic><topic>DNA-directed RNA polymerase</topic><topic>Female</topic><topic>Health risk assessment</topic><topic>Health risks</topic><topic>Humans</topic><topic>Logistic Models</topic><topic>Lung diseases</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Myopathy</topic><topic>Neoplasms - blood</topic><topic>Neoplasms - complications</topic><topic>Neoplasms - immunology</topic><topic>Nuclear Proteins - immunology</topic><topic>Patients</topic><topic>Ribonucleic acid</topic><topic>Risk</topic><topic>RNA</topic><topic>RNA polymerase</topic><topic>RNA-Binding Proteins - immunology</topic><topic>Scleroderma</topic><topic>Scleroderma, Systemic - blood</topic><topic>Scleroderma, Systemic - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shah, Ami A.</creatorcontrib><creatorcontrib>Xu, George</creatorcontrib><creatorcontrib>Rosen, Antony</creatorcontrib><creatorcontrib>Hummers, Laura K.</creatorcontrib><creatorcontrib>Wigley, Fredrick M.</creatorcontrib><creatorcontrib>Elledge, Stephen J.</creatorcontrib><creatorcontrib>Casciola‐Rosen, Livia</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>Calcium &amp; 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 &amp; Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Arthritis &amp; rheumatology (Hoboken, N.J.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shah, Ami A.</au><au>Xu, George</au><au>Rosen, Antony</au><au>Hummers, Laura K.</au><au>Wigley, Fredrick M.</au><au>Elledge, Stephen J.</au><au>Casciola‐Rosen, Livia</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Brief Report: Anti–RNPC‐3 Antibodies As a Marker of Cancer‐Associated Scleroderma</atitle><jtitle>Arthritis &amp; rheumatology (Hoboken, N.J.)</jtitle><addtitle>Arthritis Rheumatol</addtitle><date>2017-06</date><risdate>2017</risdate><volume>69</volume><issue>6</issue><spage>1306</spage><epage>1312</epage><pages>1306-1312</pages><issn>2326-5191</issn><eissn>2326-5205</eissn><abstract>Objective Prior studies have demonstrated an increased risk of cancer‐associated scleroderma in patients with anti–RNA polymerase III (anti–RNAP III) autoantibodies as well as in patients who are triple‐negative for anticentromere (anti‐CENP), anti–topoisomerase I (anti–topo I), and anti–RNAP III (also known as anti‐POL) autoantibodies (referred to as CTP negative). In a recent study of 16 CTP‐negative scleroderma patients with coincident cancer, 25% of the patients were found to have autoantibodies to RNPC‐3, a member of the minor spliceosome complex. This investigation was undertaken to validate the relationship between anti–RNPC‐3 antibodies and cancer and examine the associated clinical phenotype in a large sample of scleroderma patients. Methods Scleroderma patients with cancer were assayed for anti‐CENP, anti–topo I, anti–RNAP III, and anti–RNPC‐3 autoantibodies. Disease characteristics and the cancer–scleroderma interval were compared across autoantibody groups. The relationship between autoantibody status and cancer‐associated scleroderma was assessed by logistic regression. Results Of 318 patients with scleroderma and cancer, 70 (22.0%) were positive for anti–RNAP III, 54 (17.0%) were positive for anti–topo I, and 96 (30.2%) were positive for anti‐CENP. Twelve patients (3.8% of the overall group or 12.2% of CTP‐negative patients) were positive for anti–RNPC‐3. Patients with anti–RNPC‐3 had a short cancer–scleroderma interval (median 0.9 years). Relative to patients with anti‐CENP, patients with anti–RNPC‐3 and those with anti–RNAP III had a &gt;4‐fold increased risk of cancer within 2 years of scleroderma onset (for anti–RNPC‐3–positive patients, odds ratio [OR] 4.3, 95% confidence interval [95% CI] 1.10–16.9 [P = 0.037]; for anti–RNAP III–positive patients, OR 4.49, 95% CI 1.98–10.2 [P &lt; 0.001]). Patients with anti–RNPC‐3 had severe restrictive lung disease, gastrointestinal disease, Raynaud's phenomenon, and myopathy. Conclusion Anti–RNPC‐3 autoantibodies, similar to anti–RNAP III autoantibodies, are associated with an increased risk of cancer at the onset of scleroderma. These data suggest the possibility of cancer‐induced autoimmunity in this subset of patients with scleroderma.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>28217959</pmid><doi>10.1002/art.40065</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record>
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source MEDLINE; Wiley Online Library Journals Frontfile Complete; Alma/SFX Local Collection
subjects Adult
Antibodies
Autoantibodies
Autoantibodies - blood
Autoantibodies - immunology
Autoimmunity
Biomarkers - blood
Cancer
Confidence intervals
DNA topoisomerase
DNA-directed RNA polymerase
Female
Health risk assessment
Health risks
Humans
Logistic Models
Lung diseases
Male
Middle Aged
Myopathy
Neoplasms - blood
Neoplasms - complications
Neoplasms - immunology
Nuclear Proteins - immunology
Patients
Ribonucleic acid
Risk
RNA
RNA polymerase
RNA-Binding Proteins - immunology
Scleroderma
Scleroderma, Systemic - blood
Scleroderma, Systemic - immunology
title Brief Report: Anti–RNPC‐3 Antibodies As a Marker of Cancer‐Associated Scleroderma
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