Anti-U11/U12 RNP antibodies in systemic sclerosis: a new serologic marker associated with pulmonary fibrosis.
OBJECTIVE
To characterize a new serum autoantibody in patients with systemic sclerosis (SSc) directed against U11/U12 RNP and to identify the clinical features associated with this autoantibody.


METHODS
We identified autoantibodies directed against the U11/U12 RNP complex in sera of patients with SSc and confirmed antibody specificity by immunoprecipitation, reverse transcriptase-polymerase chain reaction, and Southern blotting. We determined the prevalence of these antibodies in SSc and their specificity for SSc. We compared anti-U11/U12 RNP autoantibody-positive and negative SSc patients on demographic, disease classification, clinical variables, and survival.


RESULTS
We identified 33 patients with anti-U11/U12 RNP antibodies. In 2 consecutive series of SSc patients first seen at 10-year intervals (1994-1995 and 2004-2005), the prevalence of anti-U11/U12 RNP antibody-positive patients was 15 of 462 (3.2%). Seventeen (52%) of these 33 patients had limited cutaneous involvement. All patients had Raynaud's phenomenon and 82% had gastrointestinal (GI) involvement. None had "intrinsic" pulmonary arterial hypertension. The most significant clinical difference between anti-U11/U12 antibody-positive and negative cohorts was the prevalence of lung fibrosis, which occurred in 79% of the anti-U11/U12 RNP antibody-positive patients versus 37% of the anti-U11/U12 RNP antibody-negative patients (P < 0.0001). GI involvement was also significantly increased in the anti-U11/U12 RNP antibody-positive group. Patients with anti-U11/U12 RNP antibodies and pulmonary fibrosis had a 2.25-fold greater risk of death than anti-U11/U12 RNP negative patients with pulmonary fibrosis.


CONCLUSIONS
Anti-U11/U12 RNP antibodies are present in the sera of approximately 3% of patients with SSc and are a marker for lung fibrosis, which is often severe.
Fertig
Noreen
N
University of Pittsburgh, Pittsburgh, PA 15213, USA.
Domsic
Robyn T
RT
Rodriguez-Reyna
Tatiana
T
Kuwana
Masataka
M
Lucas
Mary
M
Medsger
Thomas A
TA
Feghali-Bostwick
Carol A
CA
D000328:Adult; D000918:Antibody Specificity / Q000276:immunology; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D047468:Immunoprecipitation; D008297:Male; D008875:Middle Aged; D011658:Pulmonary Fibrosis / Q000097:blood* / Q000175:diagnosis / Q000401:mortality; D017411:Ribonucleoproteins, Small Nuclear / Q000276:immunology*; D012595:Scleroderma, Systemic / Q000097:blood* / Q000150:complications / Q000276:immunology*; D015996:Survival Rate
D001323:Autoantibodies; D015415:Biomarkers; D017411:Ribonucleoproteins, Small Nuclear; C552126:U11-U12 small nuclear ribonucleoprotein