Persistent lymphopenia after kidney transplantation: increased mortality and decreased homeostatic mechanisms
IntroductionKidney transplant (KTx) recipients commonly develop transient lymphopenia due to treatment with alemtuzumab, rabbit anti-thymocyte globulin (rATG) or other conditions. However, persistent lymphopenia lasting for years has not been studied in detail. The goal of this study was to determin...
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Frontiers Media S.A.
2025-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1605794/full |
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| author | Yun Liang Byron Smith Walter Park Zhihao Li Ahmed Abdelrheem Esma Kesik Mateo Velasquez Mejia Kevin Pavelko Kevin Pavelko Erik Jessen Tambi Jarmi Girish K. Mour Sumi S. Nair Mark D. Stegall Mark D. Stegall Mark D. Stegall |
| author_facet | Yun Liang Byron Smith Walter Park Zhihao Li Ahmed Abdelrheem Esma Kesik Mateo Velasquez Mejia Kevin Pavelko Kevin Pavelko Erik Jessen Tambi Jarmi Girish K. Mour Sumi S. Nair Mark D. Stegall Mark D. Stegall Mark D. Stegall |
| author_sort | Yun Liang |
| collection | DOAJ |
| description | IntroductionKidney transplant (KTx) recipients commonly develop transient lymphopenia due to treatment with alemtuzumab, rabbit anti-thymocyte globulin (rATG) or other conditions. However, persistent lymphopenia lasting for years has not been studied in detail. The goal of this study was to determine the prevalence of persistent lymphopenia, evaluate its association with mortality and investigate possible mechanisms by which it occurs. MethodsWe retrospectively studied peripheral blood lymphocyte and leukocyte counts in 7307 adult, solitary renal transplant recipients transplanted between 1/2006 to 12/2020. ResultsWhile leukocyte counts generally remained within the normal range, lymphocyte counts 3 years after KTx were below normal in 31% (compared to 14% pretransplant and 54% at 1 year). Increasing severity of lymphopenia at 3 years was associated with increasing risk of mortality. The major risk factors for lymphopenia at 3 years were: receiving alemtuzumab or rATG for induction or the treatment of rejection, increasing recipient age, pretransplant dialysis, a low lymphocyte count pretransplant, and having a prior kidney transplant. Mass cytometry immunophenotyping at 3 years showed that B cells, NK cells and all T cell subsets (CD4, CD8, naïve, memory, etc.) decreased with decreasing lymphocyte counts. This included fewer recent thymic emigrants, naïve T cells, and stem-cell like memory T cells (TSCM), suggesting an impaired homeostasis of peripheral T cells. PD-1 expression was increased with decreasing lymphocyte counts in T and B cells and in most T cell subsets including CD4 TSCM, CD4 and CD8 naïve cells, and CD4 recent thymic emigrants. DiscussionWe conclude that persistent lymphopenia might be partially due to impaired homeostatic mechanisms in T, B and NK cells and might be a simple, useful biomarker for individualizing patient management. |
| format | Article |
| id | doaj-art-c3f2fe2bd7f9464fb1c043b0538df8e4 |
| institution | OA Journals |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-c3f2fe2bd7f9464fb1c043b0538df8e42025-08-20T02:07:51ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-06-011610.3389/fimmu.2025.16057941605794Persistent lymphopenia after kidney transplantation: increased mortality and decreased homeostatic mechanismsYun Liang0Byron Smith1Walter Park2Zhihao Li3Ahmed Abdelrheem4Esma Kesik5Mateo Velasquez Mejia6Kevin Pavelko7Kevin Pavelko8Erik Jessen9Tambi Jarmi10Girish K. Mour11Sumi S. Nair12Mark D. Stegall13Mark D. Stegall14Mark D. Stegall15Department of Surgery, Mayo Clinic, Rochester, MN, United StatesDivision of Clinical Trials and Biostatistics, Mayo Clinic, Rochester, MN, United StatesWilliam J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, MN, United StatesWilliam J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, MN, United StatesWilliam J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, MN, United StatesWilliam J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, MN, United StatesWilliam J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, MN, United StatesImmune Monitoring Core, Mayo Clinic, Rochester, MN, United StatesDepartment of Immunology, Mayo Clinic, Rochester, MN, United StatesDivision of Computational Biology, Mayo Clinic, Rochester, MN, United StatesDivision of Transplantation Medicine, Mayo Clinic, Jacksonville, FL, United StatesDivision of Nephrology, Mayo Clinic, Scottsdale, AZ, United StatesDivision of Nephrology, Mayo Clinic, Scottsdale, AZ, United StatesDepartment of Surgery, Mayo Clinic, Rochester, MN, United StatesDivision of Clinical Trials and Biostatistics, Mayo Clinic, Rochester, MN, United StatesDepartment of Immunology, Mayo Clinic, Rochester, MN, United StatesIntroductionKidney transplant (KTx) recipients commonly develop transient lymphopenia due to treatment with alemtuzumab, rabbit anti-thymocyte globulin (rATG) or other conditions. However, persistent lymphopenia lasting for years has not been studied in detail. The goal of this study was to determine the prevalence of persistent lymphopenia, evaluate its association with mortality and investigate possible mechanisms by which it occurs. MethodsWe retrospectively studied peripheral blood lymphocyte and leukocyte counts in 7307 adult, solitary renal transplant recipients transplanted between 1/2006 to 12/2020. ResultsWhile leukocyte counts generally remained within the normal range, lymphocyte counts 3 years after KTx were below normal in 31% (compared to 14% pretransplant and 54% at 1 year). Increasing severity of lymphopenia at 3 years was associated with increasing risk of mortality. The major risk factors for lymphopenia at 3 years were: receiving alemtuzumab or rATG for induction or the treatment of rejection, increasing recipient age, pretransplant dialysis, a low lymphocyte count pretransplant, and having a prior kidney transplant. Mass cytometry immunophenotyping at 3 years showed that B cells, NK cells and all T cell subsets (CD4, CD8, naïve, memory, etc.) decreased with decreasing lymphocyte counts. This included fewer recent thymic emigrants, naïve T cells, and stem-cell like memory T cells (TSCM), suggesting an impaired homeostasis of peripheral T cells. PD-1 expression was increased with decreasing lymphocyte counts in T and B cells and in most T cell subsets including CD4 TSCM, CD4 and CD8 naïve cells, and CD4 recent thymic emigrants. DiscussionWe conclude that persistent lymphopenia might be partially due to impaired homeostatic mechanisms in T, B and NK cells and might be a simple, useful biomarker for individualizing patient management.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1605794/fullkidney transplantlymphopeniamortalityinductionimmunosuppression |
| spellingShingle | Yun Liang Byron Smith Walter Park Zhihao Li Ahmed Abdelrheem Esma Kesik Mateo Velasquez Mejia Kevin Pavelko Kevin Pavelko Erik Jessen Tambi Jarmi Girish K. Mour Sumi S. Nair Mark D. Stegall Mark D. Stegall Mark D. Stegall Persistent lymphopenia after kidney transplantation: increased mortality and decreased homeostatic mechanisms Frontiers in Immunology kidney transplant lymphopenia mortality induction immunosuppression |
| title | Persistent lymphopenia after kidney transplantation: increased mortality and decreased homeostatic mechanisms |
| title_full | Persistent lymphopenia after kidney transplantation: increased mortality and decreased homeostatic mechanisms |
| title_fullStr | Persistent lymphopenia after kidney transplantation: increased mortality and decreased homeostatic mechanisms |
| title_full_unstemmed | Persistent lymphopenia after kidney transplantation: increased mortality and decreased homeostatic mechanisms |
| title_short | Persistent lymphopenia after kidney transplantation: increased mortality and decreased homeostatic mechanisms |
| title_sort | persistent lymphopenia after kidney transplantation increased mortality and decreased homeostatic mechanisms |
| topic | kidney transplant lymphopenia mortality induction immunosuppression |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1605794/full |
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