Clinical Significance of Anti-U1 RNP Antibodies Recognizing The Conformation Structure on U1 RNA/70-kd Protein Complex in Patients with Mixed Connective Tissue Disease

Abstract

Objectives: To study the clinical significance of anti-U1 ribonucleoprotein (RNP) antibodies recognizing the conformational structure of the U1 RNA/70-kd protein complex in patients with mixed connective tissue disease (MCTD). Methods: Antibodies recognizing the conformational structure of U1 RNP were detected in sera from 185 MCTD patients by comparing results obtained with enzyme-linked immunosorbent assays (ELISAs) using recombinant 70-kd, A and C proteins as the antigen sources (P-ELISA) with results obtained with ELISAs making use of those proteins plus in vitro-transcribed U1 RNA (C-ELISAs). Results: Fifteen of the 185 MCTD sera were positive in C-ELISAs but negative in P-ELISAs. Immunoprecipitation assays showed that 13 of those 15 sera contained anti-U1 RNP antibodies that specifically recognized the conformational structure of the U1 RNA/70-kd protein complex. Comparison of the clinical characteristics demonstrated that 69% of patients with anti-U1 RNA/70-kd protein complex antibodies also fulfilled the criteria for systemic lupus erythematosus (SLE). Moreover, the frequencies of almost all clinical features associated with SLE were higher in patients with antibodies against the U1 RNA/70-kd protein complex than in those without the antibodies; in particular, the frequencies of CNS lupus and positivity for anti-double stranded DNA antibodies were significantly higher in patients positive for anti-U1 RNA/70-kd protein complex antibodies. Conclusions: These findings suggest that MCTD patients positive for anti-U1 RNA/70-kd complex antibodies that specifically recognize the conformational structure of the complex exhibit characteristic clinical features strongly associated with SLE and may represent a special subset of MCTD.