Abstract Introduction Antisynthetase syndrome (ASyS) is a rare autoimmune disorder characterized by a triad of myositis, arthritis, and interstitial lung disease (ILD), and by the presence of anti-aminoacyl-tRNA synthetases. Among them, anti-Jo-1 is the most common, whereas anti-PL-12 is associated to severe ILD and worse outcomes. The ILD pattern often appears as non-specific interstitial pneumonia (NSIP) or organizing pneumonia, but usual interstitial pneumonia (UIP) is uncommon, with poor prognosis. We report a case of anti-PL-12-positive ASyS with UIP pattern, satisfactorily treated with lung transplantation. Case Presentation A 65-year-old Hispanic woman, lifelong non-smoker, initially presented with chronic arthralgias, cough, Raynaud’s phenomenon, periorbital rash, and recurrent pneumonia-like episodes. High-resolution computerized tomography showed lower lobe ground-glass opacities, traction bronchiectasis, and fibrosis suggestive of NSIP. Serologic workup revealed positive PL-12 antibodies, supporting a diagnosis of ASyS.Despite initial management with mycophenolate mofetil and low-dose prednisone, the patient developed worsening cough and dyspnea. Repeat imaging demonstrated progression to severe fibrosis with features of UIP, confirmed by surgical lung biopsy. Pulmonary function testing showed progressive restrictive disease and declining DLCO, with oxygen required at night and on exertion.Nintedanib was initiated but discontinued after three months due to intolerance. Given progressive, treatment-refractory disease, the patient was referred for lung transplantation. The patient underwent a successful bilateral lung transplant, was weaned off oxygen supplementation, and showed improved functional capacity. Discussion This case shows a rare presentation of ASyS positive for anti-PL12, a less common variant than anti-Jo-1 but is strongly associated with rapid ILD progression and worse overall survival. Although NSIP is the predominant radiographic pattern, UIP can also occur and is associated with poorer outcomes. Our patient was anti-PL12 positive and progressed from NSIP-like changes to biopsy-proven UIP despite being on immunosuppression and having intolerance to antifibrotic therapy.Lung transplantation remains the only effective option in advanced, progressive ILD.Outcomes in connective tissue disease (CTD)-associated ILD have been described to be comparable to those of IPF. Yang et al. showed similar posttransplant survival rates in non-myositis CTD-ILD to IPF. However, patients with myositis-associated ILD had significantly poorer survival at 6 months and 2 years compared with IPF (38% vs. 73% and 19% vs. 60%, respectively), reflecting the clinical complexity and management challenges of ASyS presenting with severe ILD. Such findings emphasize the key role of timely lung transplantation evaluation, especially in anti-PL12-associated disease, where early intervention provides sustained stability with functional recovery. This abstract is funded by: None
Cedano et al. (Fri,) studied this question.