title: Anti-th/to-positivity in a cohort of patients with idiopathic pulmonary fibrosis.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Rheumatology and the Interstitial Lung Disease Program, National Jewish Medical and Research Center, NJMRC, Denver, Colorado 80206, USA. fischera@njc.org
authors.forename: Aryeh
authors.initials: A
authors.lastname: Fischer
authors.forename: Frederick J
authors.initials: FJ
authors.lastname: Pfalzgraf
authors.forename: Carol A
authors.initials: CA
authors.lastname: Feghali-Bostwick
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Wright
authors.forename: Douglas
authors.initials: D
authors.lastname: Curran-Everett
authors.forename: Sterling G
authors.initials: SG
authors.lastname: West
authors.forename: Kevin K
authors.initials: KK
authors.lastname: Brown
mesh_terms: D000328:Adult; D000368:Aged; D000974:Antibodies, Antinuclear / Q000097:blood*; D002466:Cell Nucleolus / Q000276:immunology; D015331:Cohort Studies; D003120:Colorado / Q000453:epidemiology; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D008168:Lung / Q000473:pathology; D017563:Lung Diseases, Interstitial / Q000276:immunology / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011658:Pulmonary Fibrosis / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D012189:Retrospective Studies; D017411:Ribonucleoproteins, Small Nuclear / Q000276:immunology*; D015996:Survival Rate
chemical_list: D000974:Antibodies, Antinuclear; D017411:Ribonucleoproteins, Small Nuclear