Abstract and Introduction
Abstract
Objective: To analyse the prevalence, the clinical characteristics, the overall survival and the event-free survival (EFS) of SSc patients who express anti-U11/U12 RNP (RNPC-3) antibodies.
Methods: A total of 447 SSc patients from Barcelona (n = 286) and Milan (n = 161) were selected. All samples were tested using a particle-based multi-analyte technology. We compared anti-RNPC-3 positive and negative patients. Epidemiological, clinical features and survival were analysed. End-stage lung disease (ESLD) was defined if the patient developed forced vital capacity <50% of predicted, needed oxygen therapy or lung transplantation. EFS was defined as the period of time free of either ESLD or death.
Results: Nineteen of 447 (4.3%) patients had anti-RNPC-3 antibodies and interstitial lung disease (ILD) was more frequent (11, 57.9% vs 144, 33.6%, P =0.030) in individuals with anti-RNPC-3 antibodies. More patients reached ESLD in the positive group (7, 36.8% vs 74, 17.3%, P = 0.006), and a higher use of non-glucocorticoid immunosuppressive drugs was observed (11, 57.9% vs 130, 30.4%, P = 0.012). Anti-RNPC-3 positive patients had lower EFS, both in the total cohort (log-rank P =0.001), as well as in patients with ILD (log-rank P = 0.002). In multivariate Cox regression analysis, diffuse cutaneous subtype, age at onset, the presence of ILD or pulmonary arterial hypertension and the expression of anti-RNPC-3 positivity or anti-topo I were independently associated with worse EFS.
Conclusion: The presence of anti-RNPC-3 was associated with higher frequency of ILD and either ESLD or death. These data suggest anti-RNPC-3 is an independent poor prognosis antibody in SSc, especially if ILD is also present.
Introduction
ANAs are present in ~90% of sera from SSc patients.[1,2] Besides the classical autoantibodies that are part of the SSc classification criteria, several other antibodies can be found, albeit with lower prevalence, some of which clearly associate with disease phenotypes and prognosis.[2–7] The evaluation of serologic status combined with skin involvement and disease duration seems to be the best predictor of clinical outcome and prognosis.[8] One of the most common causes of death in SSc patients is interstitial lung disease (ILD). Interestingly, autoantibodies have been reported to stratify SSc according to the survival time.[3]
Antibodies against RNPs are frequently found in SSc, such as anti-U1 RNP and anti-U3 RNP antibodies.[7] Antibodies to the U11/U12 complex of spliceosome (also known as anti-U11/U12 RNP) were first described by Gilliam and Steitz in 1993.[9] Recently, clinical features of patients with anti-U11/U12, especially directed against the main antigenic target RNPC-3 have been described. This antibody was associated with serious complications of the disease such as severe gastrointestinal (GI) involvement and ILD,[10,11] as well as synchronous cancer.[12] The objective of the present study was to analyse the prevalence, the clinical characteristics, the overall survival and the event-free survival (EFS) of patients who express anti-RNPC-3 antibody in two cohorts.
Rheumatology. 2022;61(1):154-162. © 2022 Oxford University Press
