Clinical Associations of Anti-RNPC3 Autoantibodies in Mixed Connective Tissue Disease

The RNA-binding region-containing protein 3 (RNPC3) protein acts as a molecular bridge, promoting U11/U12 RNP complex formation. In previous reports, patients with systemic sclerosis (SSc) with anti-RNPC3 autoantibodies had an increased risk of interstitial lung disease (ILD), severe gastrointestinal (GI) disease, and cancer. The aim of this study was to compare phenotypic features of patients with mixed connective tissue disease (MCTD) with and without anti-RNPC3 autoantibodies.

A retrospective MCTD cohort was studied. Addressable laser bead immunoassay was used to detect anti-RNPC3 autoantibodies with <1,000 mean fluorescence intensity (MFI) as normal reference range, 1,000 to 2,999 MFI as low-titer positivity and ≥3,000 MFI as high-titer positivity. Cancer occurrence within (±) five years of MCTD diagnosis and comparison of clinical features between anti-RNPC3+ and anti-RNPC3- subgroups were analyzed.

Fifteen of 66 (23%) patients with MCTD were anti-RNPC3+, which were associated with a higher frequency of sclerodactyly (anti-RNPC3+ vs anti-RNPC3-: 100% vs 67%, P = 0.007), but their frequency in ILD and GI involvement was similar (4 of 12, 33% vs 18 of 44, 41%, P = 0.73; and 13 of 14, 93% vs 43 of 46, 93% P = 0.91, respectively). Cancer was present in 3 of 15 (20%) anti-RNPC3+ compared to 3 of 51 (5.9%) anti-RNPC3- patients (P = 0.13). Numerically, more malignancy was observed among patients with high-titer anti-RNPC3+ (unadjusted odds ratio 16.00, 95% confidence interval 0.54-484.28, P = 0.07).

Anti-RNPC3 autoantibodies were associated with a higher frequency of SSc skin involvement in patients with MCTD. Anti-RNPC3 autoantibodies, especially in high titers, might be the markers for an increased risk of cancer in MCTD that needs to be confirmed in larger cohorts.