Anti-th/to-positivity in a cohort of patients with idiopathic pulmonary fibrosis.
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.
Fischer
Aryeh
A
Division of Rheumatology and the Interstitial Lung Disease Program, National Jewish Medical and Research Center, NJMRC, Denver, Colorado 80206, USA. fischera@njc.org
Pfalzgraf
Frederick J
FJ
Feghali-Bostwick
Carol A
CA
Wright
Timothy M
TM
Curran-Everett
Douglas
D
West
Sterling G
SG
Brown
Kevin K
KK
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
D000974:Antibodies, Antinuclear; D017411:Ribonucleoproteins, Small Nuclear