ackground Antitopoisomerase I (ATA), anticentromere (ACA) and anti- RNA polymerase III (RNAP3) antibodies are included in the 2013 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for systemic sclerosis (SSc). A subset of patients with SSc satisfy criteria but may lack these specific autoantibodies, being classified as ‘triple- negative’. Methods We conducted a retrospective evaluation of triple- negative patients with SSc prevalence and clinical features among the multicentric Systemic sclerosis Progression INvestiGation registry. Results Out of 1480 patients with SSc, 295 (19.9%) were triple- negative, while 1185 (81.1%) hadSc- specific antibodies: ACA (54.3%), ATA (43.6%) and RNAP3 (2.1%). The triple- negative group showed a higher prevalence of myopathy (16.7% vs 10.1%, p=0.003), suggested by higher creatine phosphokinase (CPK) levels (126.2 vs 92.5 U/mL, p=0.002), more frequent CPK increase over 2–3 times (2.4% vs 0.2%, p=0.028). Triple- negative patients also exhibited fewer vascular complications, including digital ulcers (17.3% vs 22.8%, p=0.04) and calcinosis (8.2% vs 12.8%, p=0.027), and a higher prevalence of interstitial lung disease (p<0.001). Consistently, lower diffusing capacity for carbon monoxide (66.4% vs 70.98%, p=0.004) and forced vital capacity (97.01% vs 102.92%, p<0.001) were found in the triple- negative group. Triple- negative patients more frequently received 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), while less frequently received prostanoids (71.6% vs 85.9%, p<0.001), calcium channel blockers (80.1% vs 87.7%, p=0.005) and phosphodiesterase- 5 inhibitors (4% vs 20%, p<0.001). Conclusions A higher prevalence of myopathy and interstitial lung disease and a reduced vascular burden were found in the triple- negative patients, suggesting that the non- specific and non- routinely tested autoantibodies may identify an SSc endotype resembling sclero- myositis.
Clinical and serological features of triple autoantibody- negative patients with systemic sclerosis: insights from the multicentric SPRING registry of the Italian Society for Rheumatology / Batani, V., Cavazzana, I., Orlandi, M., De Angelis, R., Campochiaro, C., De Lorenzis, E., Natalello, G., Verardi, L., Bajocchi, G., Bellando-Randone, S., Zanframundo, G., Foti, R., Cacciapaglia, F., Cuomo, G., Ariani, A., Rosato, E., Lepri, G., Girelli, F., Riccieri, V., Zanatta, E., et al.. - In: RMD OPEN. - ISSN 2056-5933. - (2026), pp. 1-11. [10.1136/rmdopen-2025-006495]
Clinical and serological features of triple autoantibody- negative patients with systemic sclerosis: insights from the multicentric SPRING registry of the Italian Society for Rheumatology
Batani V;Orlandi M;Lumetti F;Spinella A;De Pinto M;Salvarani C;Giuggioli D;Ferri C;
2026
Abstract
ackground Antitopoisomerase I (ATA), anticentromere (ACA) and anti- RNA polymerase III (RNAP3) antibodies are included in the 2013 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for systemic sclerosis (SSc). A subset of patients with SSc satisfy criteria but may lack these specific autoantibodies, being classified as ‘triple- negative’. Methods We conducted a retrospective evaluation of triple- negative patients with SSc prevalence and clinical features among the multicentric Systemic sclerosis Progression INvestiGation registry. Results Out of 1480 patients with SSc, 295 (19.9%) were triple- negative, while 1185 (81.1%) hadSc- specific antibodies: ACA (54.3%), ATA (43.6%) and RNAP3 (2.1%). The triple- negative group showed a higher prevalence of myopathy (16.7% vs 10.1%, p=0.003), suggested by higher creatine phosphokinase (CPK) levels (126.2 vs 92.5 U/mL, p=0.002), more frequent CPK increase over 2–3 times (2.4% vs 0.2%, p=0.028). Triple- negative patients also exhibited fewer vascular complications, including digital ulcers (17.3% vs 22.8%, p=0.04) and calcinosis (8.2% vs 12.8%, p=0.027), and a higher prevalence of interstitial lung disease (p<0.001). Consistently, lower diffusing capacity for carbon monoxide (66.4% vs 70.98%, p=0.004) and forced vital capacity (97.01% vs 102.92%, p<0.001) were found in the triple- negative group. Triple- negative patients more frequently received 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), while less frequently received prostanoids (71.6% vs 85.9%, p<0.001), calcium channel blockers (80.1% vs 87.7%, p=0.005) and phosphodiesterase- 5 inhibitors (4% vs 20%, p<0.001). Conclusions A higher prevalence of myopathy and interstitial lung disease and a reduced vascular burden were found in the triple- negative patients, suggesting that the non- specific and non- routinely tested autoantibodies may identify an SSc endotype resembling sclero- myositis.
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