The initial evaluation of patients with interstitial lung disease (ILD) primarily
involves a comprehensive, active search for the cause. Autoantibody assays, which can
suggest the presence of a rheumatic disease, are routinely performed at various
referral centers. When interstitial lung involvement is the condition that allows the
definitive diagnosis of connective tissue disease and the classical criteria are met,
there is little debate. However, there is still debate regarding the significance,
relevance, specificity, and pathophysiological role of autoimmunity in patients with
predominant pulmonary involvement and only mild symptoms or formes frustes of
connective tissue disease. The purpose of this article was to review the current
knowledge of autoantibody positivity and to discuss its possible interpretations in
patients with ILD and without clear etiologic associations, as well as to enhance the
understanding of the natural history of an allegedly new disease and to describe the
possible prognostic implications. We also discuss the proposition of a new term to be
used in the classification of ILDs: lung-dominant connective tissue disease.