Differential immunoglobulin class-mediated responses to components of the U1 small nuclear ribonucleoprotein particle in systemic lupus erythematosus and mixed connective tissue disease

Abstract

The objective of this paper is to determine whether patients with systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD) possess differential IgM- and IgG-specific reactivity against peptides from the U1 small nuclear ribonucleoprotein particle (U1 snRNP). The IgM- and IgG-mediated responses against 15 peptides from subunits of the U1 snRNP were assessed by indirect enzyme linked immunosorbent assays (ELISAs) in sera from patients with SLE and MCTD and healthy individuals (n = 81, 41, and 31, respectively). Additionally, 42 laboratory tests and 40 clinical symptoms were evaluated to uncover potential differences. Binomial logistic regression analyses (BLR) were performed to construct models to support the independent nature of SLE and MCTD. Receiver operating characteristic (ROC) curves corroborated the classification power of the models. We analyzed IgM and IgG anti-U1 snRNP titers to classify SLE and MCTD patients. IgG anti-U1 snRNP reactivity segregates SLE and MCTD from nondisease controls with an accuracy of 94.1% while IgM-specific anti-U1 snRNP responses distinguish SLE from MCTD patients with an accuracy of 71.3%. Comparison of the IgG and IgM anti-U1 snRNP approach with clinical tests used for diagnosing SLE and MCTD revealed that our method is the best classification tool of those analyzed (p ≤ 0.0001). Our IgM anti-U1 snRNP system along with lab tests and symptoms provide additional molecular and clinical evidence to support the hypothesis that SLE and MCTD may be distinct syndromes.