Document resource
Introduction Topoisomerase I (ATA), anticentromere (ACA), and RNA polymerase III (RNAP3) antibodies are key biomarkers in systemic sclerosis (SSc), essential for clinical stratification and included in the 2013 ACR/EULAR criteria, although growing evidence suggests that additional, non-classical autoantibodies may also be involved in disease mechanisms. Although data on the prevalence of patients lacking the three major SSc-specific autoantibodies—commonly referred to as ‘triple-negative’—exist, evidence remains limited and inconsistent. This study aimed to assess the prevalence of triple-negative patients in the Italian multicenter SPRING registry (Systemic sclerosis Progression INvestiGation) and to characterize their clinical features, comorbidities, and treatments,Material and Methods Patients from the SPRING registry who fulfilled the 2013 ACR/EULAR classification criteria for systemic sclerosis (SSc) were included. Triple-negativity was defined as the absence of ATA, ACA, and RNAP3.Results The total cohort included 1480 SSc patients. Of these, 295 (19.9%) were classified as triple-negative. These patients were more frequently located in Central (24.5%) and Southern Italy (22.1%) compared to Northern regions (16.7%) (p=0.004). Triple-negative patients showed a higher prevalence of nucleolar (29.2% vs. 13.1%) and speckled (38.6% vs. 12.5%) ANA patterns (p=0.001 for both). They also exhibited a greater prevalence of myopathy (16.7% vs. 10.1%, p=0.003), with higher mean CPK levels (126.2 vs. 92.5 U/mL, p=0.002) and more frequent CPK increases of 2–3 times (2.4% vs. 0.2%, p=0.028) and more than 3 times the upper limit of normal (3.2% vs. 0.6%, p=0.035). Interstitial lung disease (ILD) was also more common in triple-negative patients (p<0.001), and was associated with lower DLCO (66.4% vs. 70.98%, p=0.004) and FVC (97.01% vs. 102.92%, p<0.001). Vascular involvement was significantly less frequent in triple-negative patients, who showed a lower prevalence of digital ulcers (17.3% vs. 22.8%, p=0.04) and calcinosis (8.2% vs. 12.8%, p=0.027).Therapeutic strategies also differed between the groups: triple-negative patients were more frequently treated with corticosteroids (79.3% vs. 67.9%, p=0.003), cyclophosphamide (43.4% vs. 26%, p<0.001), and azathioprine (38.5% vs. 22.3%, p=0.002), and less frequently with prostanoids (71.6% vs. 85.9%, p<0.001), calcium-channel blockers (80.1% vs. 87.7%, p=0.005), and PDE5 inhibitors (4% vs. 20%, p<0.001).Conclusions Nearly 20% of the patients in our cohort were triple-negative and characterized by a higher prevalence of myopathy and interstitial lung disease (ILD), a lower incidence of vascular complications, and more frequent use of immunosuppressants, features suggestive of a specific clinical endotype, possibly resembling scleromyositis. The association of this serological profile with a defined clinical phenotype supports the need for targeted investigations to clarify its pathogenic relevance.Abstract P.061 Figure 1Immunological profile (fig 1) and comparison of demographic, autoantibody, comorbidity characteristics (2A)and disease features (2B) between groups