Session Information
Title: Systemic Sclerosis, Fibrosing Syndromes and Raynaud's - Pathogenesis, Animal Models and Genetics
Session Type: Abstract Submissions (ACR)
Background/Purpose: Research on systemic sclerosis (SSc)-associated interstitial lung disease (ILD) has been hindered by the paucity of lung tissues, as SSc patients with lung involvement are not routinely biopsied. To gain further insights into the pathogenesis of lung fibrosis in SSc, we used lung tissue microarrays (TMAs) for the detection of 4 proteins of interest in SSc-associated ILD and idiopathic pulmonary fibrosis (IPF).
Methods: Lung tissues were obtained from the explanted lungs of patients undergoing lung transplantation. Normal lung tissues were obtained from controls. H&E sections were used for the selection of suitable regions. These regions were used for obtaining 1 mm cores. A TMA was constructed containing 117 cores from patients with SSc-associated ILD, IPF, and normal controls. Sections from the TMA block were used for detection of TTF-1, thrombomodulin, laminin, and Smad4 using immunohistochemistry (IHC). Distribution and levels of expression were qualitatively assessed using light microscopy.
Results: TTF-1, thrombomodulin, laminin, and Smad4 were detected in all cores on the TMA slide. The distribution of the proteins differed in normal lungs compared to fibrotic lungs since the two subepithelial layers in normal lungs are closely apposed in the absence of fibrosis. We observed subtle differences in distribution and levels of protein expression between SSc and IPF. TTF-1 expression appeared reduced in areas of fibrosis and inflammation in both diseases. Thrombomodulin staining of airway basal cells was weaker and patchier in SSc than IPF. Laminin expression was reduced in areas of fibrosis in both SSc and IPF, but IPF lungs showed stronger laminin staining around vessels compared to SSc lungs. Nuclear Smad4 expression was more prominent and more widespread in perivascular smooth muscle cells of SSc than IPF lungs.
Conclusion: Lung TMAs are useful to simultaneously compare localization and expression levels of proteins in lung tissues from multiple patients and controls. Our initial IHC findings suggest that differences exist in the distribution and levels of TTF-1, thrombomodulin, laminin, and Smad4, and such differences can be identified using TMAs.
Disclosure:
F. Schneider,
None;
C. A. Feghali-Bostwick,
None.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/detection-of-proteins-in-lung-tissues-of-patients-with-systemic-sclerosis-using-tissue-microarrays/