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

Research output: Research - peer-reviewArticle

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 >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 < 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.

LanguageEnglish (US)
Pages1306-1312
Number of pages7
JournalArthritis and Rheumatology
Volume69
Issue number6
DOIs
StatePublished - Jun 1 2017

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Antibodies
Neoplasms
Autoantibodies
RNA Polymerase III
Cytidine Triphosphate
Type I DNA Topoisomerase
Odds Ratio
Confidence Intervals
immune RNA
Spliceosomes
Raynaud Disease
Gastrointestinal Diseases
Muscular Diseases
Autoimmunity
Lung Diseases
Logistic Models
Phenotype

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology

Cite this

Brief Report : Anti–RNPC-3 Antibodies As a Marker of Cancer-Associated Scleroderma. / Shah, Ami A.; Xu, George; Rosen, Antony; Hummers, Laura K.; Wigley, Fredrick M.; Elledge, Stephen J.; Casciola-Rosen, Livia.

In: Arthritis and Rheumatology, Vol. 69, No. 6, 01.06.2017, p. 1306-1312.

Research output: Research - peer-reviewArticle

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title = "Brief Report: Anti–RNPC-3 Antibodies As a Marker of Cancer-Associated Scleroderma",
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 >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 < 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.",
author = "Shah, {Ami A.} and George Xu and Antony Rosen and Hummers, {Laura K.} and Wigley, {Fredrick M.} and Elledge, {Stephen J.} and Livia Casciola-Rosen",
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AU - Shah,Ami A.

AU - Xu,George

AU - Rosen,Antony

AU - Hummers,Laura K.

AU - Wigley,Fredrick M.

AU - Elledge,Stephen J.

AU - Casciola-Rosen,Livia

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N2 - 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 < 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.

AB - 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 < 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.

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