Unique association of extreme elevation of cell free DNA and histologic patterns of intra-alveolar injury among lung transplant recipients
Background: Donor-derived cell-free DNA (dd-cfDNA) is a valuable biomarker for allograft injury, but its association with various histopathologic injury patterns as specified in the Lung Allograft Standardized Histological Analysis (LASHA) protocol remains unclear. This study evaluates the relations...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-08-01
|
| Series: | JHLT Open |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2950133425001004 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849389486682669056 |
|---|---|
| author | Zehra Dhanani Omar Al Omari Alonso Marquez Kartik Shenoy Fatima Anjum |
| author_facet | Zehra Dhanani Omar Al Omari Alonso Marquez Kartik Shenoy Fatima Anjum |
| author_sort | Zehra Dhanani |
| collection | DOAJ |
| description | Background: Donor-derived cell-free DNA (dd-cfDNA) is a valuable biomarker for allograft injury, but its association with various histopathologic injury patterns as specified in the Lung Allograft Standardized Histological Analysis (LASHA) protocol remains unclear. This study evaluates the relationship between various histopathologic findings as per the LASHA protocol, dd-cfDNA levels including extreme molecular injury (EMI), and allograft outcomes. Methods: We conducted a retrospective analysis of lung transplant recipients at a single center (2022-2024). A total of 84 patients with 589 dd-cfDNA samples were analyzed, with 124 samples having corresponding transbronchial biopsy (TBBX) and bronchoalveolar lavage (BAL) data. EMI was defined as dd-cfDNA > 5%. Multivariate regression analyses examined associations between histopathologic findings—including hemosiderin-laden macrophages (HLM) and organizing pneumonia (OP)—clinical comorbidities, EMI, and allograft outcomes. Results: EMI was observed in 29% of the cohort and was significantly associated with CLAD (p = 0.04), diabetes (p = 0.009), and elevated DSAs (p = 0.03). EMI was also more frequently detected in Black patients. On histopathology, OP was present in 11.2% of TBBX samples, while 8.9% had HLM. Patients with OP had significantly higher median dd-cfDNA levels compared to those without OP (p < 0.05) and exhibited lymphocytic-predominant BAL (p < 0.001). HLM was more prevalent in Black patients and in those with clinical or radiographic suspicion of OP, even in the absence of OP on histopathology. Conclusion: Our study highlights novel associations between dd-cfDNA, histopathologic findings, comorbidities, race, and allograft injury, emphasizing the need for personalized monitoring and risk stratification in lung transplantation and to explore mechanisms underlying the observed disparities. |
| format | Article |
| id | doaj-art-066daed46e7740bf91446ae1464cd002 |
| institution | Kabale University |
| issn | 2950-1334 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JHLT Open |
| spelling | doaj-art-066daed46e7740bf91446ae1464cd0022025-08-20T03:41:57ZengElsevierJHLT Open2950-13342025-08-01910030510.1016/j.jhlto.2025.100305Unique association of extreme elevation of cell free DNA and histologic patterns of intra-alveolar injury among lung transplant recipientsZehra Dhanani0Omar Al Omari1Alonso Marquez2Kartik Shenoy3Fatima Anjum4Thoracic Medicine and Surgery, Temple University Hospital, Philadelphia, PA; Corresponding author: Zehra Dhanani, Department of Thoracic Medicine and Surgery, Temple University Hospital, 3401 North Broad Street, Philadelphia, PA 19140.Thoracic Medicine and Surgery, Temple University Hospital, Philadelphia, PAThoracic Medicine and Surgery, Temple University Hospital, Philadelphia, PAThoracic Medicine and Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia, PAThoracic Medicine and Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia, PABackground: Donor-derived cell-free DNA (dd-cfDNA) is a valuable biomarker for allograft injury, but its association with various histopathologic injury patterns as specified in the Lung Allograft Standardized Histological Analysis (LASHA) protocol remains unclear. This study evaluates the relationship between various histopathologic findings as per the LASHA protocol, dd-cfDNA levels including extreme molecular injury (EMI), and allograft outcomes. Methods: We conducted a retrospective analysis of lung transplant recipients at a single center (2022-2024). A total of 84 patients with 589 dd-cfDNA samples were analyzed, with 124 samples having corresponding transbronchial biopsy (TBBX) and bronchoalveolar lavage (BAL) data. EMI was defined as dd-cfDNA > 5%. Multivariate regression analyses examined associations between histopathologic findings—including hemosiderin-laden macrophages (HLM) and organizing pneumonia (OP)—clinical comorbidities, EMI, and allograft outcomes. Results: EMI was observed in 29% of the cohort and was significantly associated with CLAD (p = 0.04), diabetes (p = 0.009), and elevated DSAs (p = 0.03). EMI was also more frequently detected in Black patients. On histopathology, OP was present in 11.2% of TBBX samples, while 8.9% had HLM. Patients with OP had significantly higher median dd-cfDNA levels compared to those without OP (p < 0.05) and exhibited lymphocytic-predominant BAL (p < 0.001). HLM was more prevalent in Black patients and in those with clinical or radiographic suspicion of OP, even in the absence of OP on histopathology. Conclusion: Our study highlights novel associations between dd-cfDNA, histopathologic findings, comorbidities, race, and allograft injury, emphasizing the need for personalized monitoring and risk stratification in lung transplantation and to explore mechanisms underlying the observed disparities.http://www.sciencedirect.com/science/article/pii/S2950133425001004Organizing pneumoniaHemosiderin laden macrophagesAllograft injuryChronic lung allograft dysfunctionImmune-mediated injury |
| spellingShingle | Zehra Dhanani Omar Al Omari Alonso Marquez Kartik Shenoy Fatima Anjum Unique association of extreme elevation of cell free DNA and histologic patterns of intra-alveolar injury among lung transplant recipients JHLT Open Organizing pneumonia Hemosiderin laden macrophages Allograft injury Chronic lung allograft dysfunction Immune-mediated injury |
| title | Unique association of extreme elevation of cell free DNA and histologic patterns of intra-alveolar injury among lung transplant recipients |
| title_full | Unique association of extreme elevation of cell free DNA and histologic patterns of intra-alveolar injury among lung transplant recipients |
| title_fullStr | Unique association of extreme elevation of cell free DNA and histologic patterns of intra-alveolar injury among lung transplant recipients |
| title_full_unstemmed | Unique association of extreme elevation of cell free DNA and histologic patterns of intra-alveolar injury among lung transplant recipients |
| title_short | Unique association of extreme elevation of cell free DNA and histologic patterns of intra-alveolar injury among lung transplant recipients |
| title_sort | unique association of extreme elevation of cell free dna and histologic patterns of intra alveolar injury among lung transplant recipients |
| topic | Organizing pneumonia Hemosiderin laden macrophages Allograft injury Chronic lung allograft dysfunction Immune-mediated injury |
| url | http://www.sciencedirect.com/science/article/pii/S2950133425001004 |
| work_keys_str_mv | AT zehradhanani uniqueassociationofextremeelevationofcellfreednaandhistologicpatternsofintraalveolarinjuryamonglungtransplantrecipients AT omaralomari uniqueassociationofextremeelevationofcellfreednaandhistologicpatternsofintraalveolarinjuryamonglungtransplantrecipients AT alonsomarquez uniqueassociationofextremeelevationofcellfreednaandhistologicpatternsofintraalveolarinjuryamonglungtransplantrecipients AT kartikshenoy uniqueassociationofextremeelevationofcellfreednaandhistologicpatternsofintraalveolarinjuryamonglungtransplantrecipients AT fatimaanjum uniqueassociationofextremeelevationofcellfreednaandhistologicpatternsofintraalveolarinjuryamonglungtransplantrecipients |