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.