This article on antibodies to Sm and RNP is part of a series on immunologic testing guidelines (1–5). The introduction to the series outlines the full methodology for obtaining data, grading the literature, combining the information from multiple sources, and for developing recommendations (1).
The Sm antigen was named after a patient, Smith, who had systemic lupus erythematosus (SLE). Antibodies to Sm were identified in 1966 by immunodiffusion (ID) to a phosphate-buffered saline extract of calf thymus (subsequently called extractable nuclear antigen [ENA]) and by hemagglutination (HA) (6). The antigen to which anti-Sm antibodies bind consists of a series of proteins: B, B', D, E, F, and G complexed with small nuclear RNAs: U1, U2, U4–6, and U5. These complexes of nuclear proteins and RNAs are called small nuclear ribonucleoprotein particles (snRNPs); they are important in the splicing of precursor messenger RNA (7), an integral step in the processing of RNA transcribed from DNA.
The anti-Sm immune reaction consists of multiple antibodies binding to multiple protein antigens (8); thus the anti-Sm antibody is better described as an antibody system.
Antibodies to the RNP antigen (originally called anti-Mo) were identified using ID in sera of patients with SLE by Mattioli and Reichlin in 1971 (9). The term RNP stems from the early observation that its antigenic activity could be destroyed by treatment with ribonuclease and trypsin (9); thus it was a ribonucleoprotein or “RNA protein” antigen (10), whereas the Sm antigen was resistant to such treatment (6). In 1971, Sharp et al (11) described a group of patients with a syndrome characterized by features of SLE, inflammatory muscle disease, and scleroderma, with an absence of renal disease and called it mixed connective tissue disease (MCTD). The sera of these patients contained antibodies to ENAs measured by passive hemagglutination. Subsequent studies showed that ENA contained both the Sm and RNP antigens (10–18) and that the patients described by Sharp et al were reacting with RNP (13). In 1979, Lerner and Steitz (8) demonstrated that both the Sm and RNP antigens were located on the U1 snRNP; therefore anti-RNP is sometimes referred to as anti–U1 RNP and anti–U1 snRNP antibodies.
The dogma regarding anti-Sm states it is found only in diseased individuals and is specific for SLE (19); furthermore, it is a criterion for the classification of SLE (18, 20, 21). The dogma regarding anti-RNP states it is found in rheumatic diseases such as SLE, Sjögren's syndrome (SS), rheumatoid arthritis (RA), polymyositis (PM), and systemic sclerosis (SSc) (22–24). High titers of anti-RNP are a requisite for the diagnosis of MCTD (13, 22, 23).
The purpose of this study was to carefully examine the literature, using established guidelines, to determine the sensitivity, specificity, and predictive values of anti-Sm and anti-RNP in the diagnosis of SLE and related diseases and their clinical associations, and to determine whether titers of these antibodies varied with any of these clinical features.