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. Conclusion. 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.