Environmental triggers of autoimmunity in anti-synthetase syndrome: the lungs under the spot light.

The prevalence of interstitial lung involvement in anti-synthetase syndrome (anti-SS) may be as high as 70% and is a major contributor to morbidity and mortality. Histidyl-tRNA synthetase (Jo-1) is the most common autoantigenic target among the aminoacyl-tRNA synthetases. We report two well documented anti-SS cases where it was observed significant exposure to a known inhaled offending antigen, development of a lymphocytic interstitial lung disease (ILD) and negative auto-antibodies, interpreted at first as hypersensitivity pneumonitis. Only after 14 and 30 months, respectively, the development of systemic symptoms compatible with anti-SS and anti-Jo-1 was observed. A growing body of evidence suggests that the lungs are the environment in which Jo-1 autoimmunity may be initiated and propagated. The description of the clinical and laboratorial evolution of these patients together with accumulated evidence of biological plausibility support the hypothesis that anti-SS can follow an episode of lung inflammation secondary to inhaled antigen exposure.