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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?

SUBMITTER: Shah AA

PROVIDER: S-EPMC5449218 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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

Shah Ami A AA Xu George G Rosen Antony A Hummers Laura K LK Wigley Fredrick M FM Elledge Stephen J SJ Casciola-Rosen Livia L

Arthritis & rheumatology (Hoboken, N.J.) 20170601 6

<h4>Objective</h4>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 au ...[more]

PMID: 28217959

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Project description:ObjectiveTo examine the association between anti-interferon-inducible protein 16 (anti-IFI-16) antibodies and clinical features of scleroderma.MethodsSera from a discovery sample of 94 patients with scleroderma and 47 healthy controls were assayed for anti-IFI-16 antibodies by enzyme-linked immunosorbent assay, and associations were examined using regression analyses. Since anti-IFI-16 autoantibodies were found to be strongly associated with digital gangrene in the discovery sample, a subsequent case-control study (with subjects matched 1:1 on disease duration) was designed for further exploration. Cases were patients with scleroderma and digital gangrene, while controls were patients with scleroderma and Raynaud's phenomenon alone (n = 39 matched pairs). Nonparametric, unadjusted matched pairs analysis as well as univariate and multivariable conditional logistic regression analyses were performed.ResultsIn the discovery sample, anti-IFI-16 antibodies were more prevalent in patients with scleroderma than in healthy controls (18% versus 2%; P = 0.01). Patients with anti-IFI-16 antibodies, compared to anti-IFI-16 antibody-negative patients, were more likely to have limited scleroderma (77% versus 46%; P = 0.03), a longer disease duration (median 15.2 years [interquartile range 10.6-18.3] versus 6.0 years [interquartile range 3.4-13.8]; P < 0.01), digital gangrene (24% versus 4%; P = 0.02), and a low diffusing capacity for carbon monoxide (DLco) (P < 0.01). In the case-control study, 35 (45%) of 78 patients were anti-IFI-16 antibody positive. Anti-IFI-16 antibody levels were significantly higher in cases with digital gangrene than in matched controls (P = 0.02). In analyses adjusted for age, cutaneous scleroderma subtype, smoking, and DLco, high anti-IFI-16 antibody levels were associated with the presence of digital gangrene (adjusted odds ratio 2.3, 95% confidence interval 1.0-5.6, P = 0.05). The odds of having digital gangrene increased with higher anti-IFI-16 antibody titers, in a dose-dependent manner.ConclusionAnti-IFI-16 antibodies are associated with digital gangrene in patients with scleroderma. Longitudinal prospective studies exploring anti-IFI-16 antibodies as a disease biomarker, and biologic studies investigating the pathogenicity of these antibodies, are warranted.

Project description:Introduction/objectivesScleroderma is a rare complication in taxanes therapy. Although individual cases of taxanes-induced scleroderma have been reported, the clinical manifestation and treatment outcomes were reviewed and summarized rarely. This study reported a patient who developed diffuse scleroderma and possible scleroderma renal crisis after paclitaxel therapy for ureter cancer.MethodA PubMed literature review on published cases of taxanes-induced scleroderma up until April 2022 was included for analysis.ResultsThe search identified 27 patients with adequate information for analysis. Of the 28 patients, including the one presented here, 22 were female. Peripheral edema was the most common symptom in all but one patient, and often accompanied by erythema in 11. Symptoms usually occurred in half of the patients within the 4th course of treatment. Skin lesions gradually progressed to skin fibrosis, and extended proximally. Internal organ involvements were uncommon. Antinuclear antibody tests were positive occasionally, but anti-Scl70 and anti-centromere usually were negative. Taxanes therapy was discontinued, continued and unavailable in 21, 3, and 4 patients, respectively. Corticosteroids for skin lesions with or without immunosuppressive drugs were given to 15 patients. Of 25 patients with available skin outcomes, 19 improved. There was no significant skin improvement between those who did or did not receive skin treatment (62.5% vs. 75.0%, p = 0.37). Skin usually improved after discontinuing taxanes.ConclusionTaxanes-induced scleroderma is different from idiopathic scleroderma. Physicians should be aware of this condition in order to provide early diagnosis and apply appropriate management in order to avoid serious complications from severe skin sclerosis. Key Points • Scleroderma is a rare but unique and serious complication of taxanes therapy • Skin manifestations and distribution are similar to idiopathic scleroderma, but vascular phenomenon, internal organ involvement and scleroderma-associated auto-antibodies are presented rarely. Skin improvement usually occurs shortly after discontinuing taxanes • The role of immunosuppressive therapy in treating taxanes-induced scleroderma is not clear.

Project description:We previously reported a contemporaneous onset of cancer and scleroderma in patients with anti-RNA polymerase III antibodies, and we identified a biologic link between cancer and scleroderma. This investigation was designed to further evaluate whether autoantibody status and other characteristics are associated with cancer and a clustering of cancer with scleroderma onset.Logistic regression analysis was performed to assess the relationship of 2 outcomes, cancer (model 1) and a short (±2 years) cancer-scleroderma interval (model 2), with autoantibody status and scleroderma covariates.Of 1,044 scleroderma patients, 168 (16.1%) had cancer. In the adjusted model 1, only older age at scleroderma onset (odds ratio 1.04 [95% confidence interval 1.02-1.05]) and white race (odds ratio 2.71 [95% confidence interval 1.22-6.04]) were significantly associated with an increased overall risk of cancer. In the adjusted model 2, only anti-RNA polymerase III positivity (odds ratio 5.08 [95% confidence interval 1.60-16.1]) and older age at scleroderma onset (odds ratio 1.04 [95% confidence interval 1.00-1.08]) were significantly associated with a short cancer-scleroderma interval. While anti-RNA polymerase III positivity was associated with a short cancer-scleroderma interval independent of age at scleroderma onset, the cancer-scleroderma interval shortened with older age at scleroderma onset in other antibody groups (Spearman's correlation P < 0.05), particularly among patients with anti-topoisomerase I antibodies and patients who were negative for anticentromere, anti-topoisomerase I, and anti-RNA polymerase III antibodies.Increased age at scleroderma onset is strongly associated with cancer risk overall. While anti-RNA polymerase III status is an independent marker of coincident cancer and scleroderma at any age, a clustering of cancer with scleroderma is also seen in patients with anti-topoisomerase I and other autoantibody specificities who develop scleroderma at older ages.

Dataset Information

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

Publications

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

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