Journal of Heart and Lung Transplantation最新文献

{"title":"Comparative whole-exome sequencing of ambulatory patients and transplant recipients with idiopathic dilated cardiomyopathy.","authors":"Ju-Hee Lee, Jinhwa Kong, Seulgi Kim, Bong-Jo Kim, Hae Young Lee, Junho Hyun, Jae-Joong Kim, Hyun-Young Park, Myeong-Chan Cho, Sang Cheol Kim, Sang Eun Lee, Ali Torkamani","doi":"10.1016/j.healun.2026.07.022","DOIUrl":"10.1016/j.healun.2026.07.022","url":null,"abstract":"<p><strong>Background: </strong>Idiopathic dilated cardiomyopathy (DCM) is a major cause of advanced heart failure and heart transplantation (HTx), yet the genetic correlates of progression to HTx and transplant-relevant arrhythmic phenotypes remain incompletely defined. We examined the genetics of idiopathic DCM in a Korean population, focusing on HTx/death and arrhythmic outcomes, to identify adverse outcome-linked genotype-phenotype associations.</p><p><strong>Methods: </strong>Whole-exome sequencing was performed in 202 Korean patients with idiopathic DCM, including 56 HTx recipients and 146 ambulatory patients, and compared the findings with 1093 population-based controls. Genotype-phenotype correlations were analyzed for major clinical outcomes, including HTx, death, arrhythmias, and left ventricular functional recovery.</p><p><strong>Results: </strong>Pathogenic/likely pathogenic variants were identified in 32% of patients (38% in HTx vs 30% in ambulatory patients). TTN was the most frequently affected gene overall (12%), but LMNA variants predominated in HTx recipients (20% vs 4%, p = 0.001). LMNA carriers showed substantially higher odds of HTx/death (OR 14.65, 95% CI 3.32-139.31; FDR p<0.001), and strong association with arrhythmias, including ventricular tachyarrhythmias and atrial fibrillation. Both missense and loss-of-function LMNA variants were associated with adverse outcomes. In contrast, TNNT2 variants were observed exclusively in ambulatory patients and identified a favorable functional-recovery phenotype, with a greater likelihood of LVEF recovery ≥10 percentage points (OR 6.03, 95% CI 1.52-28.71; FDR p = 0.016).</p><p><strong>Conclusions: </strong>LMNA variants mark a high-risk transplant-trajectory phenotype in Korean idiopathic DCM. Genetic testing may aid early identification and management of candidates for advanced HF therapies, including HTx and durable MCS.</p>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148604150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Donor disposition and lung utilization following \"Not Expected to Progress\" coding in donation after circulatory death: A national registry analysis.","authors":"Brian Jafari, Lauryn Spinetta, Vaidehi Kaza, Matthias Peltz, Christopher Heid, John Murala, Suresh Keshavamurthy","doi":"10.1016/j.healun.2026.07.018","DOIUrl":"10.1016/j.healun.2026.07.018","url":null,"abstract":"<p><strong>Background: </strong>Donation-after-circulatory-death (DCD) lung transplantation expands access for waitlisted patients, but uncertainty regarding donor progression may lead centers to decline offers using refusal code 753 (\"DCD donor neurological function/not expected to arrest\"). We sought to characterize the disposition of these donors and center practices in their allocation.</p><p><strong>Methods: </strong>Using national registry match-run data from January 2021 through June 2024 linked with Organ Procurement and Transplant Network (OPTN) transplant data, we identified DCD donors from whom lung offers were generated. Donors declined at least once with code 753 were classified as not expected to progress (NEP). Donor progression, organ procurement, and post-transplant survival were compared with standard DCD (S-DCD) donors.</p><p><strong>Results: </strong>Among 6,140 NEP donors, 3,687 (60.0%) progressed to circulatory death and had at least one organ procured. Among progressed NEP donors, lungs were recovered from 908 donors (24.6%), and 670 donors ultimately yielded at least one transplanted lung. Post-transplant survival did not differ between linked recipients of NEP and S-DCD lungs (log-rank p = 0.15).</p><p><strong>Conclusions: </strong>Many DCD donors declined using code 753 ultimately progressed after withdrawal of life-sustaining therapy, with lungs recovered in only a minority of these cases. The uncertainty surrounding donor progression may restrict access to DCD lung transplantation for waitlisted patients. Standardized DCD assessment, donor management, and policy guidance may help centers manage uncertainty when fielding DCD offers.</p>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148592060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Misdiagnosed as idiopathic pulmonary arterial hypertension: Methylmalonic acidemia as a reversible cause of pediatric pulmonary hypertension.","authors":"Yan Wu, Yuan-Rui Deng, Xiao-Pei Cui, Sheng-Song Zhu, Jiang-Shan Tan, Song Hu, Lu Hua","doi":"10.1016/j.healun.2026.07.021","DOIUrl":"10.1016/j.healun.2026.07.021","url":null,"abstract":"<p><strong>Background: </strong>Methylmalonic acidemia (MMA)-induced pulmonary hypertension (PH) is a rare but treatable cause of pediatric PH, often misdiagnosed as idiopathic pulmonary arterial hypertension (IPAH).</p><p><strong>Methods: </strong>We conducted a 10-year, multicenter retrospective study of children with clinically unexplained PH. Thirteen patients with MMA-PH were compared to 113 with idiopathic or hereditary PAH (IPAH/HPAH) regarding clinical features, hemodynamics, and outcomes.</p><p><strong>Results: </strong>MMA-PH accounted for 2.7% of pediatric PH cases. Patients presented younger (7±4 vs. 11±5 years, p=0.008) and exhibited higher rates of growth failure (84.6% vs. 15.9%, p<0.001), anorexia/malnutrition (76.9% vs. 14.2%, p<0.001), recurrent pneumonia (46.2% vs. 13.3%, p=0.003), microscopic hematuria (84.6% vs. 1.8%, p<0.001), and proteinuria (31% vs. 4.4%, p=0.007) than IPAH/HPAH. All had the combined MMA subtype with markedly elevated homocysteine (median 87 µmol/L vs. 18 µmol/L, p<0.001). With metabolic therapy (hydroxocobalamin, betaine, etc.) and short-term pulmonary vasodilators, all achieved complete clinical and hemodynamic remission within 1 year. Median follow-up was 7.0 years; no relapse occurred.</p><p><strong>Conclusions: </strong>Elevated total homocysteine and multisystem involvement should prompt metabolic screening in children with unexplained PH. Early diagnosis and metabolite-targeted treatment can lead to sustained, nearly curative outcomes, distinguishing MMA-PH from IPAH/HPAH. Routine homocysteine testing is recommended in the diagnostic workup of pediatric PH.</p>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148592032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"When \"not a candidate\" becomes a verdict: Reframing intensive care for patients with advanced heart failure.","authors":"Diana De Oliveira Gomes, Shashank S Sinha, Vanessa Blumer","doi":"10.1016/j.healun.2026.07.023","DOIUrl":"10.1016/j.healun.2026.07.023","url":null,"abstract":"<p><p>The designation \"not an advanced heart failure candidate\" is applied to patients deemed ineligible for heart transplantation or durable left ventricular assist device (LVAD) therapy at a specific point in time. While this designation accurately captures a therapeutic boundary, it is increasingly conflated with broader notions of futility, diminished prognosis, and reduced appropriateness for cardiac intensive care unit (CICU) admission. This conflation is both clinically inaccurate and potentially harmful. Transplant and LVAD candidacy are determined by a narrow, time-sensitive, and often modifiable set of criteria that do not necessarily reflect whether a patient can benefit from invasive hemodynamic monitoring, decongestion, guideline-directed medical therapy initiation, rhythm or conduction interventions, or coronary or peripheral revascularization. Contemporary data demonstrate that acute decompensated heart failure now accounts for most cardiogenic shock cases encountered in contemporary CICUs, a population in which advanced therapy ineligibility is common yet in whom thoughtful critical care may yield meaningful hemodynamic improvement, end-organ recovery, and reassessment of candidacy. This perspective argues for a triage framework that evaluates CICU appropriateness across 3 independent domains: acute physiologic need, reversibility of the index derangement, and longitudinal prognosis aligned with patient preferences. Advanced therapy ineligibility should close one door, not determine how many remain open.</p>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148592131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinct metabolomic and lipidomic profiles across donation after circulatory death recovery strategies reveal a common signature associated with primary graft dysfunction.","authors":"Elizabeth J Bashian, Sariah Hyacinth, Charles D Nicoli, Thomas F O'Shea, Samantha L Nelson, Anit Tyagi, Logan Boyle, Nicholas R Teman, Amrut V Ambardekar, Andrew Gelman, Wanzhu Zhao, Michael T Cain, Jordan R H Hoffman, Benjamin J Kopecky","doi":"10.1016/j.healun.2026.06.017","DOIUrl":"10.1016/j.healun.2026.06.017","url":null,"abstract":"<p><p>Donation after circulatory death (DCD) heart transplantation has expanded the donor pool, but the biologic consequences of different recovery strategies remain incompletely understood. Using coronary sinus blood obtained immediately following reperfusion, we performed metabolomic profiling in 31 DCD heart transplant recipients and lipidomic profiling in a nested cohort of 11 recipients with various DCD procurement methods as follows: thoraco-abdominal normothermic regional perfusion (n=10); normothermic machine perfusion (n=10), or cold oxygenated rapid recovery (n=11). Partial least squares discriminant analysis demonstrated distinct metabolomic clustering according to procurement strategy. Moderate or severe PGD occurred in 16 recipients (51.6%) and was associated with depletion of tricarboxylic acid (TCA) cycle and redox metabolites together with accumulation of acylcarnitines and amino-acid catabolic intermediates, consistent with impaired mitochondrial energetics, oxidative stress, and membrane injury. Despite distinct procurement-specific metabolic phenotypes, PGD was associated with a common metabolic signature characterized by impaired mitochondrial energetics, oxidative stress, acylcarnitine accumulation, and phospholipid remodeling, highlighting potential mechanistic targets for graft preservation and risk stratification.</p>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148361288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibody-mediated rejection after heart transplantation: Diagnostic gaps, suboptimal outcomes, and emerging tools.","authors":"Jose B Cruz Rodriguez, Deepak Acharya","doi":"10.1016/j.healun.2026.06.018","DOIUrl":"10.1016/j.healun.2026.06.018","url":null,"abstract":"","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148361261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical course and outcomes of antibody-mediated rejection after heart transplant in the contemporary era.","authors":"Bin Q Yang, Mahmoud Elesawy, Sofia Laux, Elena Deych, Amanda Fernandes, Vikram Pattanayak, Kristen E Wong, Lana Tsao, Daniel A Zlotoff, Antonia Kreso, Joel D Schilling, Gregory D Lewis","doi":"10.1016/j.healun.2026.06.005","DOIUrl":"10.1016/j.healun.2026.06.005","url":null,"abstract":"<p><strong>Background: </strong>Antibody-mediated rejection (AMR) after heart transplant (HT) is associated with increased risk of mortality and graft loss. Contemporary studies delineating AMR presentation, management, and response to treatment are lacking, especially for patients who do not have typical immunohistological evidence of rejection (biopsy-negative, BN-AMR). In this study, we sought to describe the prevalence and clinical course of BN-AMR compared to biopsy-positive (BP-AMR) patients in a multicenter HT population.</p><p><strong>Methods: </strong>We conducted a retrospective analysis of all adult HT recipients at 2 academic medical centers. AMR was further divided into BP-AMR and BN-AMR, depending on their endomyocardial biopsy findings. The primary outcome was death and secondary outcome was a composite of death, retransplant, and new International Society of Heart and Lung Transplant grade 2 or 3 coronary artery vasculopathy.</p><p><strong>Results: </strong>A total of 742 patients were included in this study. We found that AMR occurred in 10% of HT recipients and was associated with worse overall survival compared to those with only cellular rejection or no rejection. BN-AMR accounted for 33% of AMR cases. Compared to BP-AMR, BN-AMR was diagnosed later, less aggressively treated, and associated with high morbidity and mortality. The long-term outcomes between BP-AMR and BN-AMR were similarly poor, with 5-year mortality approaching 50% after diagnosis.</p><p><strong>Conclusions: </strong>AMR after HT is associated with poor clinical outcomes and BN-AMR is common. Future studies should focus on incorporating novel tools for earlier detection of AMR and investigating AMR sub-phenotypes and optimal modes of treatment.</p>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148277604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic implications of the updated ISHLT definition for severe graft dysfunction: An analysis from the International PGD Consortium and UNOS Databases.","authors":"N K Dhingra, A D Devore, S A Hall, K K Khush, S Chih, L Truby, M Signorile, F Foroutan, J Guzman Bofarull, K Takeda, E Rodenas-Alesina, J Han, G Kim, L Potena, J Lerman, H J Ross, M Farrero Torres, M G Crespo-Leiro, M Rivas-Lasarte, R Moayedifar, L Hastenteufel, C-P S Fan, D Couto Mallon, H Luikart, E Henricksen, M Sabatino, M Tremblay-Gravel, P-E Noly, R J Miller, A Zuckermann, M Farr, V Rao, A K Martin, Y Moayedi","doi":"10.1016/j.healun.2026.05.032","DOIUrl":"10.1016/j.healun.2026.05.032","url":null,"abstract":"<p><strong>Purpose: </strong>The proposed 2024 ISHLT consensus definition for severe graft dysfunction after heart transplant (HT) expands the 2014 criteria by including de novo intra-aortic balloon pump (IABP) support as diagnostic for severe dysfunction. We evaluated the prognostic implications of this reclassification using data from the International Consortium on PGD (herein 'Consortium') and United Network for Organ Sharing (UNOS) registries.</p><p><strong>Methods: </strong>Heart Transplant (HT) recipients were categorized into the following groups (1) meeting 2014 severe PGD criteria, (2) reclassified as severe early graft dysfunction (EGD) by the 2024 criteria based on a newly placed IABP within 24 h of HT, or (3) not meeting severe PGD criteria. KM survival curves and log-rank tests were used to compare unadjusted survival. A multivariable Cox regression model was used to determine the association of group status on 1 year mortality.</p><p><strong>Results: </strong>A total of 7239 HT recipients with relevant data were included in this analysis: 4087 in the Consortium and 3152 from UNOS. In the Consortium cohort, 361 (8.8%), 116 (2.8%), and 3610 (88.3%) patients comprised Groups 1, 2 and 3, respectively. Group 1 had more pre-transplant temporary and durable mechanical circulatory support, along with longer ischemic times. At 1 year post-HT, mortality in patients with de novo IABP (12.1% in Consortium, 9.6% in UNOS) was significantly lower than in patients with 2014 severe PGD (36.3% in Consortium, 27.2% in UNOS), and more closely resembled those without severe PGD (7.4% in Consortium, 5.6% in UNOS) [Log-rank p < 0.001 in both groups]. After adjustment for potential confounders, both reclassified patients with a de novo IABP [Group 2: HR 0.30 (0.17-0.51)] and patients without severe PGD [Group 3: HR 0.17 (0.14-0.22)] had significantly reduced risk of 1 year mortality compared to those with 2014 severe PGD (P<0.001) in the Consortium. These findings were replicated in the UNOS population.</p><p><strong>Conclusion: </strong>In this analysis of two contemporary, multicentre databases, patients who received an isolated de novo IABP within the first 24 h postoperatively had significantly better survival than those who were dependent on extra-corporeal membrane oxygenation (ECMO) or ventricular assist devices after HT. Combining these disparate patient groups in the new severe PGD definition may obscure prognostic differences and diminish recognition of the most severe PGD phenotype.</p>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2026-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148210713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of kidney ischemic time on two-year survival and graft outcomes after simultaneous heart-kidney transplantation: Analysis of the OPTN registry.","authors":"Naoki Tadokoro, Michael M Givertz, Taylor Nordan, Vanessa S Faria, Sho Takemoto, Noelle C Bryan, Mansoo Cho, Tanujit Dey, Mandeep R Mehra, Akinobu Itoh","doi":"10.1016/j.healun.2026.06.001","DOIUrl":"10.1016/j.healun.2026.06.001","url":null,"abstract":"<p><strong>Background: </strong>Prolonged kidney cold ischemic time (CIT) exceeding 18 to 24 hours worsens outcomes in isolated kidney transplantation, but its impact on simultaneous heart-kidney transplantation (SHKT) remains unclear.</p><p><strong>Methods: </strong>We retrospectively analyzed 2363 adult primary SHKT recipients from the OPTN database (2014 to 2024), stratified by kidney CIT at the cohort median: CIT ≤17 hours (n = 1251 [52.9%]) and CIT >17 hours (n = 1112 [47.1%]). Baseline differences were adjusted using inverse probability of treatment weighting (IPTW) based on 12 covariates selected from clinical relevance and prior literature. Two-year mortality was assessed using IPTW-adjusted Kaplan-Meier analysis and doubly robust Cox proportional hazards regression. Kidney graft failure was evaluated using Fine-Gray subdistribution hazard models with death as a competing event.</p><p><strong>Results: </strong>After IPTW adjustment, excellent covariate balance was achieved (all absolute standardized mean differences <0.10; weighted pseudo-population: n = 1225 vs n = 1082). Two-year IPTW-adjusted survival was 87.0% (95% CI, 84.7-89.5) in the CIT ≤17 hours group vs 82.0% (95% CI, 79.2-84.9) in the CIT >17 hours group (weighted log-rank p = 0.006). In doubly robust Cox analysis, CIT >17 hours was independently associated with higher 2-year mortality (HR, 1.44; 95% CI, 1.10-1.87; p = 0.007). Fine-Gray analysis showed no significant association with kidney graft failure (SHR, 1.16; 95% CI, 0.78-1.71; p = 0.47), while the subdistribution hazard for death was significantly elevated (SHR, 1.51; 95% CI, 1.13-2.01; p = 0.005).</p><p><strong>Conclusions: </strong>Prolonged kidney CIT in SHKT is independently associated with increased 2-year mortality but not kidney graft failure, with excess mortality driven by infection-related death.</p>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2026-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148211572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatial transcriptomics reveals differences in bronchus-associated lymphoid tissue composition in stable and rejecting human lung allografts.","authors":"Alexander N Wein, Changxu Fan, Vladimir Sukhov, Junedh M Amrute, Jon H Ritter, Amit I Bery, Maxim Artyomov, Alexander S Krupnick, Ruben G Nava, Andrew E Gelman, Kory J Lavine, Daniel Kreisel","doi":"10.1016/j.healun.2026.06.003","DOIUrl":"10.1016/j.healun.2026.06.003","url":null,"abstract":"<p><strong>Background: </strong>Lung allograft rejection is determined by pathologist grading of transbronchial biopsies (TBBx) according to criteria established by the International Society of Heart and Lung Transplantation (ISHLT). Lymphocytic bronchiolitis (LB), described as mononuclear cells in bronchiolar submucosa, exhibits significant histologic overlap with bronchus-associated lymphoid tissue (BALT) leading to diagnostic uncertainty. Additionally, the role of BALT in tolerance and rejection is debated. We sought to characterize lymphoid aggregates in ISHLT acute cellular rejection (ACR) grades A0 or A3 biopsies to better understand the spectrum of BALT and rejection lesions.</p><p><strong>Methods: </strong>TBBx were reviewed for the presence of BALT. Representative A0 and A3 biopsies were selected for spatial transcriptomics and multiplex immunofluorescence microscopy.</p><p><strong>Results: </strong>Spatial transcriptomics of allograft biopsies enabled unbiased identification of BALT and rejection lesions via neighborhood analysis. CXCL9/10⁺ T and PDL1/L2⁺ myeloid cell clusters were enriched in A0 BALT, while an NKG7⁺CD8⁺ T cell cluster was enriched in A3 BALT. Higher expression of CXCL9 and CXCL10 in the BALT correlated with A0 grade. Computational methods identified occult areas of lymphoid aggregates in rejecting lung parenchyma with similarity to rejection lesions. A3 BALT and rejection lesions showed substantial similarities. Immunofluorescence confirmed the key transcriptomics findings.</p><p><strong>Conclusions: </strong>This study suggests a relationship between the immune microenvironment in BALT and graft rejection. Additionally, lymphoid infiltration in allografts graded A3 may be more widespread than apparent on Hematoxylin and Eosin (H&E) stain.</p>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2026-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148210835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}