Association of LTBP2 with acute exacerbation (AE) of IPF
(A) Comparison of serum LTBP2 concentrations between patients with (n=24) and without (n=92) AE of IPF at IPF diagnosis or within 6 months of IPF diagnosis. Statistical comparison was performed using the Mann–Whitney U test. (B–D) Immunohistochemistry images of diffuse alveolar damage in an autopsied lung from a patient with AE of IPF, stained by Hematoxylin–Eosin, anti-LTBP2 antibody, and anti-αSMA antibody, respectively. Intra-alveolar LTBP2-positive hyaline membranes (arrows) and edematous alveolar walls with many αSMA-positive cells were observed. Hyaline membranes were not stained when a normal rabbit polyclonal IgG was used as the primary antibody. (E–G) Immunofluorescence images of the same lung section (color: green = αSMA; red = LTBP2; white = lineage markers (CD45, CD324, CD31, podoplanin, and h-caldesmon)). (E) LTBP2 positivity was found in or around interstitial myofibroblasts (triangles) and in the hyaline membrane (arrow). (F) In a thickened alveolar wall, diffuse positivity for both αSMA and LTBP2 was observed. (G) Smooth muscle cells (h-caldesmon-positive cells) at a fibrotic interstitium showed positivity for LTBP2 as well as αSMA.