Publications

Publications

  • Application of Mass Cytometry Platforms to Solid Organ Transplantation. Transplantation Zhang, W., Sen, A., Pena, J. K., Reitsma, A., Alexander, O. C., Tajima, T., Martinez, O. M., Krams, S. M. 2024

    Abstract

    Transplantation serves as the cornerstone of treatment for patients with end-stage organ disease. The prevalence of complications, such as allograft rejection, infection, and malignancies, underscores the need to dissect the complex interactions of the immune system at the single-cell level. In this review, we discuss studies using mass cytometry or cytometry by time-of-flight, a cutting-edge technology enabling the characterization of immune populations and cell-to-cell interactions in granular detail. We review the application of mass cytometry in human and experimental animal studies in the context of transplantation, uncovering invaluable contributions of the tool to understanding rejection and other transplant-related complications. We discuss recent innovations that have the potential to streamline and standardize mass cytometry workflows for application to multisite clinical trials. Additionally, we introduce imaging mass cytometry, a technique that couples the power of mass cytometry with spatial context, thereby mapping cellular interactions within tissue microenvironments. The synergistic integration of mass cytometry and imaging mass cytometry data with other omics data sets and high-dimensional data platforms to further define immune dynamics is discussed. In conclusion, mass cytometry technologies, when integrated with other tools and data, shed light on the intricate landscape of the immune response in transplantation. This approach holds significant potential for enhancing patient outcomes by advancing our understanding and facilitating the development of new diagnostics and therapeutics.

    View details for DOI 10.1097/TP.0000000000004925

    View details for PubMedID 38467594

  • Impact of Induction Therapy on Rejection in Pediatric Transplantation: A Multicenter Study in the US Tajima, T., Chin, C., Desai, D. M., Fishbein, T. M., Mazariegos, G. V., Tekin, A., Venick, R., Krams, S. M., Martinez, O. M., Esquivel, C. O. LIPPINCOTT WILLIAMS & WILKINS. 2023: S495
  • 311.2: Risk factors for Epstein-Barr virus DNAemia in pediatric transplantation: A multicenter study in the United States. Transplantation Tajima, T., Bernstein, D., Boyd, S. D., Gratzinger, D., Lum, G., Sasaki, K., Tan, B., Weinberg, K., Armstrong, B., Brown, M., Chin, C., Desai, D., Fishbein, T. M., Mazariegos, G., Robien, M. A., Tekin, A., Twist, C. J., Venick, R. S., Krams, S. M., Martinez, O. M., Esquivel, C. O. 2023; 107 (10S1): 71-72

    View details for DOI 10.1097/01.tp.0000993400.94644.c0

    View details for PubMedID 37845955

  • Highlights from the 12th congress of the international pediatric transplant association, Austin, Texas 2023. Pediatric transplantation Chinnakotla, S., Esquivel, C., Twombley, K., Posfay-Barbe, K., Krams, S. M. 2023: e14592

    Abstract

    The 12th Congress of the (IPTA) event in Austin, Texas, had over 400 attendees from 40 countries. The attendees included a diverse mix of pediatric transplant professionals from several specialties including physicians, surgeons, scientists, nurses, organ procurement personnel, advance transplant providers, pharmacists, administrators, fellows, residents, and students. The 4-day event featured nearly 200 abstracts, 90 oral presentations, 24 mini oral presentations, and more than 80 poster presentations. All of these presentations encouraged vibrant discussions and supported the exchange of new clinical and basic science information regarding clinical care management, basic science research, socioeconomic, and ethical and organ donation issues relevant to pediatric transplantation. We briefly describe here the highest scored presented abstracts at IPTA 2023 that are divided into two categories: clinical and basic sciences.

    View details for DOI 10.1111/petr.14592

    View details for PubMedID 37632202

  • High-dimensional profiling of pediatric immune responses to solid organ transplantation. Cell reports. Medicine Rao, M., Amouzgar, M., Harden, J. T., Lapasaran, M. G., Trickey, A., Armstrong, B., Odim, J., Debnam, T., Esquivel, C. O., Bendall, S. C., Martinez, O. M., Krams, S. M. 2023: 101147

    Abstract

    Solid organ transplant remains a life-saving therapy for children with end-stage heart, lung, liver, or kidney disease; however, ∼33% of allograft recipients experience acute rejection within the first year after transplant. Our ability to detect early rejection is hampered by an incomplete understanding of the immune changes associated with allograft health, particularly in the pediatric population. We performed detailed, multilineage, single-cell analysis of the peripheral blood immune composition in pediatric solid organ transplant recipients, with high-dimensional mass cytometry. Supervised and unsupervised analysis methods to study cell-type proportions indicate that the allograft type strongly influences the post-transplant immune profile. Further, when organ-specific differences are considered, graft health is associated with changes in the proportion of distinct T cell subpopulations. Together, these data form the basis for mechanistic studies into the pathobiology of rejection and allow for the development of new immunosuppressive agents with greater specificity.

    View details for DOI 10.1016/j.xcrm.2023.101147

    View details for PubMedID 37552988

Publications

  • The IPTA Nashville consensus conference on post-transplant lymphoproliferative disorders after solid organ transplantation in children: IV-consensus guidelines for the management of post-transplant lymphoproliferative disorders in children and adolescents. Pediatric transplantation Allen, U. D., L'Huillier, A. G., Bollard, C. M., Gross, T. G., Hayashi, R. J., Höcker, B., Maecker-Kolhoff, B., Marks, S. D., Mazariegos, G. V., Smets, F., Trappe, R. U., Visner, G., Chinnock, R. E., Comoli, P., Danziger-Isakov, L., Dulek, D. E., Dipchand, A. I., Ferry, J. A., Martinez, O. M., Metes, D. M., Michaels, M. G., Preiksaitis, J., Squires, J. E., Swerdlow, S. H., Wilkinson, J. D., Dharnidharka, V. R., Green, M., Webber, S. A., Esquivel, C. O. 2024; 28 (5): e14781

    Abstract

    The International Pediatric Transplant Association convened an expert consensus conference to assess current evidence and develop recommendations for various aspects of care relating to post-transplant lymphoproliferative disorders (PTLD) after pediatric solid organ transplantation. This report addresses the outcomes of deliberations by the PTLD Management Working Group. A strong recommendation was made for reduction in immunosuppression as the first step in management. Similarly, strong recommendations were made for the use of the anti-CD20 monoclonal antibody (rituximab) as was the case for chemotherapy in selected scenarios. In some scenarios, there is uncoupling of the strength of the recommendations from the available evidence in situations where such evidence is lacking but collective clinical experiences drive decision-making. Of note, there are no large, randomized phase III trials of any treatment for PTLD in the pediatric age group. Current gaps and future research priorities are highlighted.

    View details for DOI 10.1111/petr.14781

    View details for PubMedID 38808744

  • Epstein-Barr virus-associated post-transplant lymphoproliferative disorders in pediatric transplantation: A prospective multicenter study in the United States. Pediatric transplantation Tajima, T., Martinez, O. M., Bernstein, D., Boyd, S. D., Gratzinger, D., Lum, G., Sasaki, K., Tan, B., Twist, C. J., Weinberg, K., Armstrong, B., Desai, D. M., Mazariegos, G. V., Chin, C., Fishbein, T. M., Tekin, A., Venick, R. S., Krams, S. M., Esquivel, C. O. 2024; 28 (4): e14763

    Abstract

    Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disorders (PTLD) is the most common malignancy in children after transplant; however, difficulties for early detection may worsen the prognosis.The prospective, multicenter, study enrolled 944 children (≤21 years of age). Of these, 872 received liver, heart, kidney, intestinal, or multivisceral transplants in seven US centers between 2014 and 2019 (NCT02182986). In total, 34 pediatric EBV+ PTLD (3.9%) were identified by biopsy. Variables included sex, age, race, ethnicity, transplanted organ, EBV viral load, pre-transplant EBV serology, immunosuppression, response to chemotherapy and rituximab, and histopathological diagnosis.The uni-/multivariable competing risk analyses revealed the combination of EBV-seropositive donor and EBV-naïve recipient (D+R-) was a significant risk factor for PTLD development (sub-hazard ratio: 2.79 [1.34-5.78], p = .006) and EBV DNAemia (2.65 [1.72-4.09], p < .001). Patients with D+R- were significantly more associated with monomorphic/polymorphic PTLD than those with the other combinations (p = .02). Patients with monomorphic/polymorphic PTLD (n = 21) had significantly more EBV DNAemia than non-PTLD patients (p < .001) and an earlier clinical presentation of PTLD than patients with hyperplasias (p < .001), within 6-month post-transplant. Among non-liver transplant recipients, monomorphic/polymorphic PTLD were significantly more frequent than hyperplasias in patients ≥5 years of age at transplant (p = .01).D+R- is a risk factor for PTLD and EBV DNAemia and associated with the incidence of monomorphic/polymorphic PTLD. Intensive follow-up of EBV viral load within 6-month post-transplant, especially for patients with D+R- and/or non-liver transplant recipients ≥5 years of age at transplant, may help detect monomorphic/polymorphic PTLD early in pediatric transplant.

    View details for DOI 10.1111/petr.14763

    View details for PubMedID 38682750

  • Application of Mass Cytometry Platforms to Solid Organ Transplantation. Transplantation Zhang, W., Sen, A., Pena, J. K., Reitsma, A., Alexander, O. C., Tajima, T., Martinez, O. M., Krams, S. M. 2024

    Abstract

    Transplantation serves as the cornerstone of treatment for patients with end-stage organ disease. The prevalence of complications, such as allograft rejection, infection, and malignancies, underscores the need to dissect the complex interactions of the immune system at the single-cell level. In this review, we discuss studies using mass cytometry or cytometry by time-of-flight, a cutting-edge technology enabling the characterization of immune populations and cell-to-cell interactions in granular detail. We review the application of mass cytometry in human and experimental animal studies in the context of transplantation, uncovering invaluable contributions of the tool to understanding rejection and other transplant-related complications. We discuss recent innovations that have the potential to streamline and standardize mass cytometry workflows for application to multisite clinical trials. Additionally, we introduce imaging mass cytometry, a technique that couples the power of mass cytometry with spatial context, thereby mapping cellular interactions within tissue microenvironments. The synergistic integration of mass cytometry and imaging mass cytometry data with other omics data sets and high-dimensional data platforms to further define immune dynamics is discussed. In conclusion, mass cytometry technologies, when integrated with other tools and data, shed light on the intricate landscape of the immune response in transplantation. This approach holds significant potential for enhancing patient outcomes by advancing our understanding and facilitating the development of new diagnostics and therapeutics.

    View details for DOI 10.1097/TP.0000000000004925

    View details for PubMedID 38467594

  • Effect of Cellular Senescence in Disease Progression and Transplantation: Immune Cells and Solid Organs. Transplantation Kirchner, V. A., Badshah, J. S., Hong, S. K., Martinez, O., Pruett, T. L., Niedernhofer, L. J. 2023

    Abstract

    Aging of the world population significantly impacts healthcare globally and specifically, the field of transplantation. Together with end-organ dysfunction and prolonged immunosuppression, age increases the frequency of comorbid chronic diseases in transplant candidates and recipients, contributing to inferior outcomes. Although the frequency of death increases with age, limited use of organs from older deceased donors reflects the concerns about organ durability and inadequate function. Cellular senescence (CS) is a hallmark of aging, which occurs in response to a myriad of cellular stressors, leading to activation of signaling cascades that stably arrest cell cycle progression to prevent tumorigenesis. In aging and chronic conditions, senescent cells accumulate as the immune system's ability to clear them wanes, which is causally implicated in the progression of chronic diseases, immune dysfunction, organ damage, decreased regenerative capacity, and aging itself. The intimate interplay between senescent cells, their proinflammatory secretome, and immune cells results in a positive feedback loop, propagating chronic sterile inflammation and the spread of CS. Hence, senescent cells in organs from older donors trigger the recipient's alloimmune response, resulting in the increased risk of graft loss. Eliminating senescent cells or attenuating their inflammatory phenotype is a novel, potential therapeutic target to improve transplant outcomes and expand utilization of organs from older donors. This review focuses on the current knowledge about the impact of CS on circulating immune cells in the context of organ damage and disease progression, discusses the impact of CS on abdominal solid organs that are commonly transplanted, and reviews emerging therapies that target CS.

    View details for DOI 10.1097/TP.0000000000004838

    View details for PubMedID 37953486

  • Impact of Induction Therapy on Rejection in Pediatric Transplantation: A Multicenter Study in the US Tajima, T., Chin, C., Desai, D. M., Fishbein, T. M., Mazariegos, G. V., Tekin, A., Venick, R., Krams, S. M., Martinez, O. M., Esquivel, C. O. LIPPINCOTT WILLIAMS & WILKINS. 2023: S495