# Deciphering the Reactivity of Autoantibodies Directed against the RNP-A, -C and 70 kDa Components of the U1-snRNP Complex: “Double or Nothing”?

## TL;DR

This study explores how different autoantibodies against the U1-snRNP complex can help distinguish between mixed connective tissue disease and systemic lupus erythematosus.

## Contribution

The study introduces the RNP index as a more informative diagnostic tool for MCTD versus SLE.

## Key findings

- The RNP index showed higher sensitivity and specificity for MCTD compared to SLE.
- No preferential association of IgG or IgM autoantibodies was found between SLE and MCTD.
- Analyzing autoantibody proportions in U1-snRNP is more informative than analyzing individual autoantibodies.

## Abstract

Background: The positivity of anti-RNP autoantibodies as biological criteria for the diagnosis of mixed connective tissue disease (MCTD) has recently divided the rheumatology community. Autoantigenicity of the U1-snRNP complex tends to generate multiple autoantibodies against RNP-A, -C and -70 KDa or Sm proteins. The aim of this study is to identify the most informative autoantibodies in clinical practice, in particular, to contribute to differential diagnosis between MCTD and systemic lupus erythematosus (SLE). Methods: Sera from 74 patients positive for anti-RNP autoantibodies were selected over a period of one year of laboratory practice. Autoantibodies directed against extractable nuclear antigen, RNP proteins (A, C, 70 KDa) and 40 kDa fragments of RNP-70 KDa were investigated by using quantitative fluoroenzymatic assay and Western blot analysis. Results: Among the 74 patients, 40 patients were diagnosed with SLE, 20 with MCTD, six with another autoimmune disease, three with SARS-CoV-2 infection, three with cancer and two were healthy. No preferential clinical association of IgG or IgM autoantibodies directed against each of the RNP proteins was found between SLE and MCTD. In contrast, the proportion of autoantibodies directed against the RNP component within the U1-snRNP complex showed a significantly higher RNP index in patients with MCTD than in those with SLE (p = 0.011), with good performance (sensitivity: 69.2%, specificity: 88.9%). Conclusions: The analysis of the proportion of the different autoantibodies directed against the U1-snRNP complex is more informative than the analysis of each autoantibody separately. A follow-up of patients could be informative about the interest of the RNP index as a predictor of disease evolution.