The pulmonary histopathologic manifestations of the anti-PL7/antithreonyl transfer RNA synthetase syndrome

Summary

The pulmonary histopathologic manifestations of the antisynthetase syndromes is poorly understood and reported. Eight cases of interstitial lung disease related to the presence of antitheonyl (PL7) transfer RNA synthetase autoantibodies along with a review of biopsy changes reported in the English literature are described. Most patients presented with dyspnea and cough, with myositis, skin changes including “mechanic's hands,” and Raynaud phenomenon. Biopsy patterns of injury included usual interstitial pneumonia (n = 4), organizing pneumonia (n = 2), nonspecific interstitial pneumonia, and lymphoid interstitial pneumonia (n = 1 each), which, in a minority of instances, contrasted with predictions by thoracic radiologists based on high-resolution computed tomographic scans. This study emphasizes the integrated clinical, radiologic, and pathologic approach to interstitial lung disease, especially in connective tissue disorders, and points out the occurrence of usual interstitial pneumonia and organizing pneumonia in this patient group where nonspecific interstitial pneumonia has been the dominant pattern of clinical interest.

Introduction

The lung is the most frequent extramuscular organ afflicted in the idiopathic inflammatory myopathies including polymyositis and dermatomyositis (DM). Clinical respiratory signs and symptoms can derive from respiratory muscle weakness, infectious complications, aspiration due to oropharyngeal dysfunction, or complications of immunosuppressive therapy [1], [2], [3], [4], [5]. The association of interstitial lung disease (ILD) and the myositis spectrum of disease is well known, and the incidence varies depending on the subclassification of the syndrome and autoantibody profiles [6], [7], [8], [9], [10], [11]. The highest incidence occurs in the so-called antisynthetase syndrome (ASS) in which patients have autoantibodies that target aminoacyl transfer RNA synthetases that catalyze the binding of specific amino acids to their cognate transfer RNA during protein synthesis [1]. Patients often present with myositis, ILD, arthritis, Raynaud phenomenon, fever, and mechanic's hands with variations in incidence dependent on the unique antiaminoacyl transfer RNA synthetase antibody [1], [3]. Anti-Jo1 (antihistidyl transfer RNA synthetase) is the most common autoantibody in this group and is associated with pulmonary disease in more than 70% of cases [1], [12]. Others include anti-PL7 (antithreonyl), anti-PL12 (antialanyl), anti-OJ (anti-isoleucyl), anti-EJ (antiglycyl), and anti-KS (antiasparaginyl), among others. Although anti-Jo1 occurs in 20% to 30% of ASSs, the second most common, anti-PL7 (antithreonyl) occurs in 3% to 17% of cases and also has a high incidence of clinical ILD [13], [14], [15], [16], [17], [18], [19]. Despite its relative frequency and its involvement of the lung, the pulmonary pathology of anti-PL7 synthetase syndrome (APL7SS) has been poorly described, with few biopsy reported cases in the literature [13], [14], [15], [16]. In this study, we report the largest study of the pulmonary histopathology of anti-PL7 pulmonary disease in conjunction with a review of the reported biopsy findings in the English literature.