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Anti-Th/To-Positivity in a Cohort of Patients with Idiopathic Pulmonary Fibrosis
ARYEH FISCHER, FREDERICK J. PFALZGRAF, CAROL A. FEGHALI-BOSTWICK, TIMOTHY M. WRIGHT, DOUGLAS CURRAN-EVERETT, STERLING G. WEST, and KEVIN K. BROWN ABSTRACT. Objective. To evaluate the presence and clinical relevance of anti-Th/To-positivity in patients with idiopathic pulmonary fibrosis (IPF). Methods. Antinuclear antibody (ANA) testing was performed in 285 patients with a clinical diagnosis of IPF and surgical lung biopsy-proven usual interstitial pneumonia. Twenty-five subjects (8.8%) were found to have a positive ANA with a nucleolar-staining pattern and were followed for 10 years. Immunoprecipitation analysis indicated that 13 of the 25 subjects had autoantibodies against Th/To antigen. Results. All subjects presented with worsening dyspnea. Pulmonary physiology and gas exchange did not differ between those with and those without a positive ANA, those with and without a nucleolar-staining ANA, and those with and without anti-Th/To antibody positivity. Retrospective review of the clinical record revealed that none of the 25 subjects with a nucleolar-staining ANA had the characteristic cutaneous features of systemic sclerosis (SSc). Four of the 13 Th/To-positive subjects had 3 of 5 criteria of limited cutaneous SSc (CREST variant), and 9 met proposed criteria for SSc sine scleroderma. None of the 12 Th/To-negative subjects had 3 or more criteria of limited cutaneous SSc (CREST variant), and only one met proposed criteria for SSc sine scleroderma. Of the 25 subjects with nucleolar-staining ANA, cumulative survival was similar between those who were Th/To-positive and those who were Th/To-negative (log-rank test, p = 0.73). Cumulative survival was similar between the 13 Th/To-positive subjects and all other 272 IPF subjects (log-rank test, p = 0.34). Conclusion. Our findings indicate that a nucleolar-staining ANA is a common finding in patients with IPF, and that antibodies against Th/To are responsible for the majority of these. Given the high specificity of Th/To-positivity for SSc, our data suggest that these subjects may have SSc sine scleroderma, and that their prognosis is no different from those with IPF. (First Release June 15 2006; J Rheumatol 2006;33:1600–5) Key Indexing Terms:
IDIOPATHIC PULMONARY FIBROSIS From the Division of Rheumatology and the Interstitial Lung Disease Program, National Jewish Medical and Research Center (NJMRC); Research Center and Division of Rheumatology, University of Colorado Health Sciences Center (UCHSC), Denver, Colorado; Carbondale Clinic, Carbondale, Illinois; Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania; Novartis Pharmaceuticals, Cambridge, Massachusetts; Departments of Biostatistics; Preventive Medicine and Biometrics; and Physiology and Biophysics; and Division of Pulmonary Sciences and Critical Care Medicine, UCHSC. A. Fischer, MD, Division of Rheumatology, Department of Medicine, NJMRC, and Division of Rheumatology, UCHSC; F.J. Pfalzgraf, MD, Chief, Rheumatology, Carbondale Clinic; C.A. Feghali-Bostwick, PhD, Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh; T.M. Wright, MD, Novartis Pharmaceuticals; D. Curran-Everett, PhD, Department of Biostatistics, NJMRC, and Departments of Preventive Medicine and Biometrics and of Physiology and Biophysics, UCHSC; S.G. West*, MD, Division of Rheumatology, Department of Medicine, UCHSC; K.K. Brown*, MD, NJMRC, and Division of Pulmonary Sciences and Critical Care Medicine, UCHSC. *Authors contributed equally to the report. Address reprint requests to Dr. A. Fischer, Division of Rheumatology, National Jewish Medical and Research Center, 1400 Jackson Street, Denver, CO 80206. E-mail: fischera@njc.org. Accepted for publication March 28, 2006.
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