Pulmonary Pathologic Manifestations of Anti-Alanyl-tRNA Synthetase (Anti–PL-12)–Related Inflammatory Myopathy

Abstract

Context.— Patients with anti–aminoacyl-tRNA synthetase syndrome (ARS), a subset of idiopathic inflammatory myopathy, have a high prevalence of lung involvement. Autoantibodies directed against alanyl-tRNA synthetase (anti–PL-12 Abs) represent 1 of the 8 autoantibodies currently described under the rubric of ARS. Objective.— To describe the clinical, radiographic, and pulmonary histopathologic findings in patients possessing anti–PL-12 autoantibodies. Design.— Patients with anti–PL-12 ARS were identified in the University of Pittsburgh Idiopathic Inflammatory Myopathy registry. Lung biopsies from 10 patients and lung explants from 2 patients with anti–PL-12 ARS were reviewed, together with chest computed tomography and clinical records. Results.— Patients primarily presented with dyspnea and variable combinations of cough, fever, mechanic's hands, Raynaud phenomenon, and skin and muscle involvement. Chest computed tomography most commonly showed lower lung zone-predominant reticular infiltrates and traction bronchiectasis, with or without honeycomb change. Surgical lung biopsies and pneumonectomies for lung transplantation revealed usual interstitial pneumonia in 8 of 12 cases (67%), nonspecific interstitial pneumonia in 2 of 12 cases (17%), and organizing pneumonia in 2 of 12 cases (17%). Lymphoplasmacytic interstitial inflammation with lymphoid aggregates was common. Conclusions.— Lung disease is often the first manifestation of anti–PL-12 ARS. There are no pathognomonic histopathologic features to distinguish anti–PL-12 ARS-related lung disease from idiopathic variants of diffuse interstitial lung disease. Increased inflammation, lymphoid aggregates, and nonspecific interstitial pneumonia–like areas in a biopsy, as well as clinical features of mechanic's hands, Raynaud phenomenon, arthritis, and fever, should prompt pathologists to suggest involvement by ARS.