Veronica Batani, Ilaria Cavazzana, Martina Orlandi, Rossella De Angelis, Corrado Campochiaro, Enrico De Lorenzis, Gerlando Natalello, Lucrezia Verardi, Gianluigi Bajocchi, Silvia Bellando-Randone, Giovanni Zanframundo, Rosario Foti, Fabio Cacciapaglia, Giovanna Cuomo, Alarico Ariani, Edoardo Rosato, Gemma Lepri, Francesco Girelli, Valeria Riccieri, Elisabetta Zanatta, Francesca Ingegnoli, Maria De Santis, Giuseppe Murdaca, Giuseppina Abignano, Pettiti Giorgio, Alessandra Della Rossa, Maurizio Caminiti, Anna Maria Iuliano, Lorenzo Beretta, Gianluca Bagnato, Ennio Lubrano, Ilenia De Andres, Luca Idolazzi, Cosimo Bruni, Marco Fornaro, Marta Saracco, Cecilia Agnes, Edoardo Cipolletta, Federica Lumetti, Amelia Spinella, Marco De Pinto, Luca Magnani, Veronica Codullo, Elisa Visalli, Carlo Iandoli, Antonietta Gigante, Greta Pellegrino, Erika Pigatto, Maria-Grazia Lazzaroni, Franco Franceschini, Francesca Motta, Antonio Tonutti, Gianna Mennillo, Marco Di Battista, Giuseppa Pagano Mariano, Federica Furini, Licia Vultaggio, Simone Parisi, Clara Lisa Peroni, Gerolamo Bianchi, Enrico Fusaro, Gian Domenico Sebastiani, Marcello Govoni, Salvatore D'Angelo, Franco Cozzi, Serena Guiducci, Andrea Doria, Carlo Salvarani, Florenzo Iannone, Maria Antonietta D'Agostino, Silvia Laura Bosello, Lorenzo Dagna, Dilia Giuggioli, Clodoveo Ferri, Marco Matucci Cerinic, Giacomo De Luca
Journal: RMD open 2026;12(2):
PMID: 42128529
BACKGROUND
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%) had SSc-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.
© Author(s) (or their employer(s)) 2026. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.
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