Recent data suggest that the presence of circulating autoantibodies is associated with specific histopathologic findings, even in the absence of characterizable CTD. Song and colleagues compared and contrasted secondary histopathologic features among three groups of patients with usual interstitial pneumonia (UIP) pattern lung injury. Group 1 (n = 39) comprised subjects with CTD-UIP; group 2 (n = 27), subjects who had idiopathic UIP with ANA or RF positivity; and group 3 (n = 34), subjects who had idiopathic UIP and were antibody negative. Presumably, the subjects in group 2 (antibody-positive, idiopathic UIP) were not considered as having CTD based on the absence of characterizable extrathoracic features or more specific autoantibodies. Among those with CTD-UIP were more germinal centers, plasma cells, and fewer fibroblastic foci than that found in all subjects with idiopathic UIP. Interestingly, however, histopathologic features differed between the subgroups of idiopathic UIP (groups 2 and 3) based on autoantibody status. Although none of the subjects with antibody-positive idiopathic UIP (group 2) had extrathoracic features of CTD, they had higher germinal center scores and more plasma cells than subjects with antibody-negative idiopathic UIP (group 3). Notably, no histopathologic features distinguished CTD-UIP (group 1) from antibody-positive idiopathic UIP (group 2). Among those subjects with idiopathic UIP (groups 2 and 3), antibody status did not affect survival, although as the authors point out, this might have been due to the small sample sizes in each group, but those with idiopathic UIP had a worse prognosis than those with CTD-UIP (group 1). The impact of circulating, albeit nonspecific, autoantibodies on the underlying histopathologic features is of interest and raises the possibility that systemic autoimmunity may be of etiologic importance in this cohort. The significance of these findings is not known, but we believe that they merit further investigation.