周一“星”视角|猪肺移植中敲除猪白细胞抗原表达可使无免疫抑制的移植物存活；老年患者中单肺与双肺移植比较：一项倾向性匹配分析

01

Constanca Figueiredo1, Che‍n Chen-Wacker1, Jawad Salman2, Marco Carvalho-Oliveira1, Thierry Siemeni Monthé3, Klaus Höffler2, Tamina Rother1, Karolin Hacker2, Emilio Valdivia1, Olena Pogozhykh1, Sabine Hammer4, Wiebke Sommer5, Yuliia Yuzefovych1, Nadine We‍nzel1, Axel Haverich2, Gregor Warnecke5, Rainer Blasczyk1

1 Institute of Transfusion Medicine and Transplant engineering, hannover Medical School, 30625 hannover, Germany.

2 Department of cardiothoracic, Transplant and Vascular Surgery, hannover Medical School, 30625 hannover, Germany.

3 Department of cardiothoracic Surgery, Jena University hospital, 07747 Jena, Germany. 

4 Institute of immunology, department of Pathobiology, University of Veterinary Medicine Vienna, 1210 Vienna, austria.

5 Department of cardiac Surgery, University of Kiel, 24105 Kiel, Germany.

Background: 

Immune rejection remains the major obstacle to long-term survival of allogeneic lung transplants. The expression of major histocompatibility complex molecules and minor histocompatibility antigens triggers allogeneic immune responses that can lead to allograft rejection. Transplant outcomes therefore depend on long-term immunosuppression, which is associated with severe side effects. To address this problem, we investigated the effect of genetically engineered transplants with permanently down-regulated swine leukocyte antigen (SLA) expression to prevent rejection in a porcine allogeneic lung transplantation (LTx) model. 

Methods: 

Minipig donor lungs with unmodified SLA expression (control group, n = 7) or with modified SLA expression (treatment group, n = 7) were used to evaluate the effects of SLA knockdown on allograft survival and on the nature and strength of immune responses after terminating an initial 4-week period of immunosuppression after LTx. Genetic engineering to down-regulate SLA expression was achieved during ex vivo lung perfusion by lentiviral transduction of short hairpin RNAs targeting mRNAs encoding β2-microglobulin and class II transactivator.

Results: 

Whereas all grafts in the control group were rejected within 3 months, five of seven animals in the treatment group maintained graft survival without immunosuppression during the 2-year monitoring period. Compared with controls, SLA-silenced lung recipients had lower donor-specific antibodies and proinflammatory cytokine concentrations in the serum.

Conclusion: 

These data demonstrate a survival benefit of SLA–down-regulated lung transplants in the absence of immunosuppression.

[CITATION]:Constanca Figueiredo, Chen Chen-Wacker, Jawad Salman, et al. Knockdown of swine leukocyte antigen expression in porcine lung transplants enables graft survival without immunosuppression, Science Translational Medicine, 2024 Jul 17;16(756):eadi9548.

[DOI]: 10.1126/scitranslmed.adi9548.

[IF]: 15.8

02

Noah Weingarten1, Atul C. Mehta2, Marie Budev2, Usman Ahmad3, James Yun3, Kenneth McCurry3, Haytham Elgharably 4

1 Department of Surgery, University of Pennsylvania, Philadelphia, PA.

2 Respiratory Institute, Department Pulmonary Medicine, Cleveland Clinic, Cleveland, OH.

3 Heart, Vascular and Thoracic Institute, Department of Cardiovascular Surgery, Cleveland Clinic, Cleveland, OH.

4 Heart, Vascular and Thoracic Institute, Department of Cardiovascular Surgery, Cleveland Clinic, Cleveland, OH.

Background: 

Single lung transplantation (SLT) is associated with worse long-term outcomes than bilateral lung transplantation (BLT), but often is performed for older adults at risk of not tolerating BLT. How do the outcomes of SLT and BLT compare among older adult recipients?

Methods: 

The Scientific Registry of Transplant Recipients database (2005-2022) was queried for lung transplant recipients 65 years of age or older. Patients were stratified by whether they underwent BLT or SLT and propensity matched. Baseline characteristics and morbidity were compared with frequentist statistics. Survival was analyzed via Kaplan-Meier estimation. Risk factors for mortality were identified with Cox regression.

Results: 

Of 9,904 included patients, 4,829 (48.8%) underwent SLT. Patients who underwent SLT had lower lung allocation scores (39.6 vs 40.6; P < 0.001), more interstitial lung disease (74.4% vs 64.6%; P < 0.001), and lower rates of bridging (0.7% vs 2.4%; P < 0.001). Groups did not differ significantly by sex, body mass index, or donor characteristics. Propensity matching resulted in 2,539 patients in each group. On matched analysis, patients undergoing SLT had shorter lengths of stay (14 days vs 18 day), lower reintubation rates (14.7% vs 19.8%), and less postoperative dialysis use (4.2% vs 6.4%; P < 0.001 for all). Patients who underwent SLT had comparable survival at 30 days (97.6% vs 97.3%; P = 0.414) and 1 year (85.5% vs 86.3%; P = 0.496), but lower survival at 5 years (45.4% vs 53.4%; P < 0.001) on matched analysis. SLT was a risk factor for 5-year mortality (adjusted hazard ratio, 1.19; P < 0.001).

Conclusion: 

In older adults, SLT is associated with less morbidity and comparable early survival relative to BLT, but lower five-year survival. SLT is reasonable to perform in older adults at high risk for not tolerating BLT.

[CITATION]: Weingarten N, Mehta AC, Budev M, et al. Single vs Double Lung Transplantation in Older Adults: A Propensity-Matched Analysis. Chest. 2024 Sep 5:S0012-3692(24)05138-9.

[DOI]: 10.1016/j.chest.2024.08.044

[IF]:9.5