Antibodies to U1-RNP are part of the clinical definition of mixed connective tissue disease (MCTD). These antibodies and other well-defined antibodies tend to arise together in affected patients. Although still speculative, hypotheses that link U1-RNP antibodies to the development of autoimmunity in MCTD and that associate U1-RNP antibodies with mechanisms of tissue injury in MCTD have emerged and are being tested. Salient features of these hypotheses include: (1) an antigen-driven response that is due to impaired clearance of potentially immunogenic self-antigens, (2) inadequate B- and T-cell tolerance to RNP autoantigens, and (3) immunogenic properties of the RNA component of targeted ribonucleoproteins. Further studies are needed to establish whether anti-RNP antibodies have prognostic importance that is relevant to practicing clinicians.
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