1878 - Circulating Anti-U11/U12 Ribonucleoprotein Antibodies in Systemic Sclerosis Are Markers of Severe Lung Fibrosis

Noreen Fertig1, Tatiana Rodriguez-Reyna1, Masataka Kuwana2, Thomas A. Medsger, Jr1, Carol A. Feghali-Bostwick1. 1University of Pittsburgh, Pittsburgh, PA; 2Keio University, Tokyo, Japan
Presentation Number: 1878

Purpose: To characterize autoantibodies against components of the minor splicesomal complex, the U11/U12 ribonucleoprotein (RNP) complex, in systemic sclerosis (SSc) patients and to identify clinical features associated with their presence.
Methods: Sera of 257 adults and 102 childhood-onset SSc patients were screened for the presence of autoantibodies directed against the low abundance U11/U12 RNP complex. The antibody specificity was confirmed by immunoprecipitation, RT-PCR and southern blotting of small nuclear RNAs (snRNA). Sera were obtained at the first visit, and updated information on clinical variables and outcomes was obtained from review of medical records. Chi square was used to compare frequencies, with Fisher’s correction when appropriate. student’s t test was used to compare continuous data. All statistical analyses were two-tailed and results were considered statistically significant if p values were less than 0.05.
Results: Anti-U11/U12 RNP antibodies were detected in the sera of 28 (5%) patients with SSc. Slightly more than half of these patients (57%) had limited cutaneous disease and none had overlap with other connective tissue disease. All patients had Raynaud phenomenon, 61% had severe digital ischemia, 82% had gastrointestinal involvement, and none of the patients had skeletal muscle or renal involvement. Anti-U11/U12 RNP autoantibodies were significantly associated with clinical, functional and/or radiographic evidence of pulmonary fibrosis (86%). Of the patients with pulmonary fibrosis, 67% had severe (FVC < 50% predicted) or end-stage (supplemental oxygen required) lung fibrosis. Three of these patients underwent lung transplant surgery. None of the patients had intrinsic pulmonary arterial hypertension (PAP>35 mmHg on echocardiogram or PAP>25 mmHg on right heart catheterization without evidence of heart or other lung diseases). Eleven (40%) died from lung disease-related complications during a mean follow-up of 6.6 years. Lung fibrosis was equally distributed among patients with diffuse and limited cutaneous skin involvement.
Conclusions: Anti-U11/U12 RNP antibodies are present in sera of patients with SSc independent of other SSc-associated autoantibodies and are a marker of severe, progressive, often fatal lung fibrosis.

 N. Fertig, None; T. Rodriguez-Reyna, None; M. Kuwana, None; T.A. Medsger, Jr, None; C.A. Feghali-Bostwick, None.