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. 2025 Jan 2;65(1):2400839.
doi: 10.1183/13993003.00839-2024. Print 2025 Jan.

Skewed adaptive immune responses are involved in alpha-1 antitrypsin deficiency emphysema

Joselyn Rojas-Quintero  1 , Scott A Ochsner  2 , Hyun-Sung Lee  3 , Christine Cong  1 , Alan Waich Cohen  1 , Adrianne S Colborg  4 , Konstantin Tsoyi  1 , Maria C Basil  5 , Edward Cantu  6 , Ivan O Rosas  1 , Neil J McKenna  2 , Raúl San-José Estépar  7 , Igor Barjaktarevic  8 , Andrew A Wilson  9 , Francesca Polverino  10
Affiliations

Skewed adaptive immune responses are involved in alpha-1 antitrypsin deficiency emphysema

Joselyn Rojas-Quintero et al. Eur Respir J. .
No abstract available

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Conflict of interest statement

Conflict of interest: E. Cantu reports grants from NIH, XVIVO Inc, CareDx and Pulmocide, consultancy fees from CSL Behring and United Therapeutics, support for attending meetings from Pulmocide Ltd, and leadership roles with International Society for Heart and Lung Transplantation (Board of Directors), UNOS Lung Committee (regional representative) and FDA (consultant for device group). I.O. Rosas reports grants from Three Lakes Foundation and Boehringer Ingelheim, and consultancy fees from Genentech Roche, Boehringer Ingelheim and Avalyn Pharmaceuticals. N.J. McKenna reports support for the present study from NIH. R. San-José Estépar reports support for the present study from NHLBI, grants or contracts from Lung Biotechnology, Insmed and Boehringer Ingelheim, consulting fees from Leuko Labs and Mount Sinai, board membership of Fundación MVision, and that they are co-founder and stockholder of Quantitative Image Solutions, and hold three patents. I. Barjaktarevic reports grants from Theravance, Viatris, Aerogen, Alpha-1 Foundation, Johnny Carson's Foundation and Takeda, consultancy fees from AstraZeneca, Sanofi/Regeneron, Grifols, Verona Pharma, Inhibrx and Takeda, and payment or honoraria for lectures, presentations, manuscript writing or educational events from AstraZeneca, Sanofi/Regeneron, Grifols, Verona Pharma, Inhibrx and Takeda. A.A. Wilson reports support for the present study from NIH, grants from Grifols NA and Beam Therapeutics, and a leadership role with Alpha-1 Foundation (Scientific Director). F. Polverino reports support for the present study from NHLBI (HL149744) and Baylor College of Medicine funds, grants from Victory Houston and Boehringer Ingelheim, consultancy fees from Sanofi-Regeneron, Verona Pharma, Genentech, AstraZeneca and Amgen, support for attending meetings from ATS, and leadership roles with European Respiratory Journal (Section Editor) and RCMB (program committee chair). The remaining authors have no potential conflicts of interest to disclose.

Figures

Figure
Figure
In A, representative pictures of peripheral lung from AATD and WT-AAT emphysematous patients triple immunostained for pan B cell marker (CD20, green), plasma cell marker (CD138, red), and follicular dendritic cell marker (CD21, cyan). The dotted line highlights a germinal center in a AATD patient. In B, FFPE lung sections from AATD and WT-AAT emphysematous patients were immunostained to assess B cell subsets in parenchyma. Data are presented as mean±SEM bars with scatter plot overlay; *P<0.05; ***P<0.001. In C, representative pictures of LF immunostained for pan B cell marker (CD20, red) and AAT protein (green), showing AAT deposits in the periphery of LFs. In D, representative pictures from WT-AAT emphysema and AATD emphysema subjects, immunostained for macrophages (CD68, red) and AAT polymers (green). The inset shows abundant accumulation of AAT polymer inside alveolar macrophages. In E, unsupervised tSNE plot of the transcriptomic signatures shows neat clustering of the AATD groups (red dots) compared to the WT-AAT (blue dots) emphysema groups. Unsupervised tSNE plot of the transcriptomic signatures shows neat clustering of ROIs from the AATD groups (highlighted by a dotted line) compared to the WT-AAT emphysema groups. In F, GSVA analysis of enriched pathways between WT-AAT (blue) and AATD (red) subjects. In G, volcano plot shows the differential gene expression in parenchyma between AATD (red) and WT-AAT (green) patients. In H, High-confidence transcriptional intersection results per ROI, showing the enrichment of B cell transcription factors. In I, cell deconvolution per ROI was performed using CIBERSORTx, and cell type enrichment between AATD (red) and WT-AAT (blue) patients are shown.
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