Anti-survival motor neuron complex antibodies as a novel biomarker for pulmonary arterial hypertension and interstitial lung disease in mixed connective tissue disease

Objective The presence of anti-U1 RNP antibodies (Abs) is critical for diagnosing MCTD. The aim of this study is to evaluate the clinical relevance of anti-survival motor neuron (SMN) complex Abs, which often coexist with anti-U1 RNP Abs. Methods A total of 158 newly diagnosed consecutive cases of SLE, SSc or MCTD with anti-U1 RNP Abs were enrolled in this multicentre observational study between April 2014 and August 2022. Serum anti-SMN complex Abs were screened by immunoprecipitation of S-35-methionine-labelled cell extracts, and associations between anti-SMN complex Abs positivity and clinical characteristics were analysed. Results Anti-SMN complex Abs were detected in 36% of MCTD patients, which was significantly higher than that in SLE (8%) or SSc (12%). Among MCTD patients classified based on the combination of the clinical features of SLE, SSc and idiopathic inflammatory myopathies, anti-SMN complex Abs showed the highest prevalence in a subset with clinical features of all three components. Anti-SMN complex Abs-positive MCTD had a higher prevalence of pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD), which are related to poor prognosis, than negative patients. Moreover, all three cases of death within 1 year of the treatment were positive for anti-SMN complex Abs. Conclusions Anti-SMN complex Abs is the first biomarker of a typical subset of MCTD which bears organ damages such as PAH and ILD.

Automated summary

This study evaluated the clinical relevance of anti-survival motor neuron (SMN) complex antibodies in patients with mixed connective tissue disease (MCTD). The results showed that the detection rate of anti-SMN complex antibodies was significantly higher in MCTD patients compared to those with systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). Furthermore, MCTD patients positive for anti-SMN complex antibodies had a higher prevalence of pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD).