Background: The increase in the use of monoclonal antibodies (mAB) as a targeted therapy for a variety of diseases has been accompanied by an increase in reports of interstitial lung abnormalities in treated patients.
Objective: Bronchoalveolar lavage (BAL) is routinely performed in these patients to rule out infection, so we sought to determine the BAL cellular pattern in individuals with mAB-induced lung disease (mAB-ILD).
Methods: We utilized a case-control study design. Among patients treated with mAB, cases were defined as those with otherwise-unexplained interstitial lung abnormalities, which resolved after cessation of treatment, while controls were defined as those with interstitial abnormalities clearly explained by other etiologies.
Results: From 2000 to 2012, we identified 9 cases and 7 controls. The mean age of the cases was 62.6 ± 26 years and 6 were female. The most common radiographic finding was diffuse ground-glass opacities. The most common BAL cellular pattern was mixed inflammation with moderate lymphocytic and mild neutrophilic alveolitis. The cases had a higher mean lymphocyte count than the controls (40.1 ± 32.6 vs. 13.1 ± 25.5, p = 0.008). The rest of the BAL cellular analyses were similar between the 2 groups. The median CD4:CD8 ratio in 7 patients with >15% lymphocytes was 0.9 (0.6-3). There was no significant difference in the CD4:CD8 ratio between the 2 groups.
Conclusions: Mixed inflammation with moderate lymphocytic and mild neutrophilic alveolitis is the most common BAL cellular pattern in patients with mAB-ILD. Such findings may be useful for the early identification of mAB-ILD.
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http://dx.doi.org/10.1159/000362521 | DOI Listing |
Respir Res
January 2025
Department of Public Health and Clinical Medicine, Section of Medicine, Umeå University, 901 87, Umeå, Sweden.
Background: In COPD, the balance between matrix metalloproteinases (MMPs) and their natural inhibitors [tissue inhibitors of metalloproteinases (TIMPs)] is shifted towards excessive degradation, reflected in bronchoalveolar lavage (BAL) as increased MMP concentrations. Because of their critical role in lung homeostasis, MMP activity is tightly regulated, but to what extent this regulation occurs through epigenetic mechanisms remains unknown.
Methods: To explore the interplay between MMPs, TIMPs, and DNA methylation (DNAm) we (1) analysed MMP-9, -12, and TIMP-1 concentrations in BAL fluid, and profiled DNAm in BAL cells from 18 COPD and 30 control subjects, (2) estimated protein-COPD relationships using multivariable regression, (3) identified protein quantitative trait methylation loci (pQTMs) with COPD as a potential modifier in a separate interaction model, and (4) integrated significant interactions with a previous COPD GWAS meta-analysis.
J Allergy Clin Immunol
January 2025
Division of Allergy, Pulmonary and Critical Care Medicine, University of Wisconsin-Madison, Madison, Wis. Electronic address:
Background: Airway inflammation has a critical role in asthma pathogenesis and pathophysiology. Yet, the molecular pathways contributing to airway inflammation are not fully known, particularly Type-2 (T2) inflammation characterized by both eosinophilia and higher FeNO levels.
Objective: To identify genes whose level of expression in epithelial brushing samples were associated with both bronchoalveolar lavage (BAL) eosinophilia and generation of FeNO.
Nat Immunol
January 2025
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Hematopoietic stem cells must mitigate myriad stressors throughout their lifetime to ensure normal blood cell generation. Here, we uncover unfolded protein response stress sensor inositol-requiring enzyme-1α (IRE1α) signaling in hematopoietic stem and progenitor cells (HSPCs) as a safeguard against myeloid leukemogenesis. Activated in part by an NADPH oxidase-2 mechanism, IRE1α-induced X-box binding protein-1 (XBP1) mediated repression of pro-leukemogenic programs exemplified by the Wnt-β-catenin pathway.
View Article and Find Full Text PDFViruses
November 2024
C.U.R.E. (University Center for Liver Disease Research and Treatment), Liver Unit, Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy.
SARS-CoV-2 infection induces a humoral immune response, producing virus-specific antibodies such as IgM, IgG, and IgA. IgA antibodies are present at mucosal sites, protecting against respiratory and other mucosal infections, including SARS-CoV-2, by neutralizing viruses or impeding attachment to epithelial cells. Since SARS-CoV-2 spreads through the nasopharynx, the specific IgAs of SARS-CoV-2 are produced quickly after infection, effectively contributing to virus neutralization.
View Article and Find Full Text PDFCells
December 2024
Immunology Service, Clinical University Hospital Virgen de la Arrixaca (HCUVA), Biomedical Research Institute of Murcia Pascual Parrilla (IMIB), 30120 Murcia, Spain.
Interstitial lung diseases (ILDs) are pathologies affecting the pulmonary interstitium and, less frequently, the alveolar and vascular epithelia. Bronchoalveolar lavage (BAL) is commonly used in ILD evaluation since it allows the sampling of the lower respiratory tract. The prognostic value of BAL cell counts in ILD is unknown.
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