Anti-synthetase syndrome in ANA and anti-Jo-1 negative patients presenting with idiopathic interstitial pneumonia

Abstract

Objectives: To describe the clinical features of patients presenting with "idiopathic" interstitial pneumonia that were diagnosed with anti-synthetase syndrome based on clinical features and positive anti-PL-7 or PL-12 antibodies.

Methods: Over a 24-month period, we evaluated 37 patients who presented with clinical features of anti-synthetase (AS) syndrome, negative anti-Jo-1 antibodies, and who were assessed for other anti-tRNA synthetase (anti-tRS) antibodies. All data were abstracted from the medical record.

Results: Nine (24%) were confirmed to have non-anti-Jo-1 positive AS syndrome based on clinical features and the presence of other anti-tRS antibodies (seven with anti-PL-7, two with anti-PL-12 antibodies). All presented with dyspnea as the initial symptom and with ILD as the first manifestation. Elevated CPK was identified in three patients but only two had muscle weakness. Pulmonary physiology revealed restriction (forced vital capacity 60% of predicted) and impaired gas transfer (diffusing capacity for carbon monoxide 40% of predicted). All had similar findings on thoracic HRCT scans, with basilar predominance of abnormalities and patterns suggestive of non-specific interstitial pneumonia and organizing pneumonia. Immunomodulatory therapies were used to treat the ILD-responses were variable, but some subjects clearly improved.

Conclusion: Anti-PL-7 and PL-12 antibodies may be more common among patients presenting with "idiopathic" interstitial pneumonia than formerly considered and should be checked in patients with features of AS syndrome despite a negative screen for anti-nuclear or anti-Jo-1 antibodies. Further research is needed to advance understanding of anti-PL-7 or anti-PL-12-positive AS syndrome, including its prognosis and optimal approaches to therapy.

Figure 1. HRCT Findings in AS Syndrome

Panels A–C display coronal slices from three patients with AS syndrome. Note the extreme basilar predominance of findings, the extensive traction bronchiectasis in Panel B, and how the opacities in all three panels hug or “pancake” the diaphragms. White arrows in Panel A and black arrows in Panel B point to the major fissures being pulled caudally from the extensive lower lobe volume loss. Similar findings are seen in Panel C. Panels D and E are transverse slices from the same patient as Panel C. The black arrow in Panel D points to the extreme caudal aspect of the middle lobe affected by extensive ground glass opacities and fraction bronchiectasis. Note the patulous esophagus. Similar findings in the lung parenchyma are seen in Panel E.