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Vascularized composite allotransplantation (VCA) is an emerging field in transplant surgery. Despite overall positive outcomes, VCA confers risk for multiple complications related to the procedure and subsequent immunosuppression. Post-transplant lymphoproliferative disorder (PTLD) is a heterogeneous group of lymphoproliferative disorders occurring after solid organ and hematopoietic stem cell transplant. A patient with PTLD after bilateral upper extremity transplantation is presented as well as a review of all known cases of PTLD after VCA, with a focus on the unique epidemiology, presentation, and treatment in this population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Zaccardelli, Lucas, LaCasce, Chandraker, Azzi and Talbot.)

The current tools for diagnosing and monitoring native kidney diseases as well as allograft rejection in transplant patients are suboptimal. Creatinine and proteinuria are non-specific and poorly sensitive markers of injury. Tissue biopsies are invasive and carry potential complications. In this article, we overview the different techniques of liquid biopsy and discuss their potential to improve patients' kidney health. Several diagnostic, predictive, and prognostic biomarkers have been identified with the ability to detect and monitor the activity of native kidney diseases as well as early and chronic allograft rejection, such as donor-derived cell-free DNA, exosomes, messenger RNA/microsomal RNA, proteomics, and so on. While the results are encouraging, additional research is still needed as no biomarker appears to be perfect for a routine application in clinical practice. Despite promising advancements in biomarkers, the most important issue is the lack of standardized pre-analytical criteria. Large validation studies and uniformed standard operating procedures are required to move the findings from bench to bedside. Establishing consortia such as the Liquid Biopsy Consortium for Kidney Diseases can help expedite the research process, allow large studies to establish standardized procedures, and improve the management and outcomes of kidney diseases and of kidney transplant recipients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors JRA and PC declared that they were editorial board members of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. This had no impact on the peer review process and the final decision. The reviewer AA declared a shared parent affiliation with the authors AN, KC, SR, MD, COB, JA, and JRA to the handling editor at the time of review., (© 2023 Nassar, Cashman, Rao, Dagher, O'Brien, Afif, Cravedi and Azzi.)

In the transplant community, research efforts exploring endogenous alternatives to inducing tolerogenic allo-specific immune responses are much needed. In this regard, CD4  +  FoxP3 + regulatory T cells (T regs ) are appealing candidates due to their intrinsic natural immunosuppressive qualities. To date, various homeostatic factors that dictate T reg survival and fitness have been elucidated, particularly the non-redundant roles of antigenic CD3 ζ /T-cell-receptor, co-stimulatory CD28, and cytokine interleukin (IL-)2 dependent signaling. Many of the additional biological signals that affect T regs remain to be elucidated, however, especially in the transplant context. Previously, we demonstrated an unexpected link between type I interferons (IFNs) and T regs in models of multiple myeloma (MM)-where MM plasmacytes escaped immunological surveillance by enhancing type I IFN signaling and precipitating upregulated T reg responses that could be overturned with specific knockdown of type I IFN signaling. Here, we elaborated on these findings by assessing the role of type I IFN signaling (IFN-α and -β) on T reg homeostasis within an alloimmune context. Specifically, we studied the induction of T regs from naïve CD4 T cells. Using in vitro and in vivo models of murine skin allotransplantation, we found that type I IFN indeed spatiotemporally enhanced the polarization of naïve CD4 T cells into FoxP3 + T regs . Notably, however, this effect was not independent of, and rather co-dependent on, ancillary cytokine signals including IL-2. These findings provide evidence for the relevance of type I IFN pathway in modulating FoxP3 + T reg responses and, by extension, stipulate an additional means of facilitating T reg fitness via type I IFNs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Eskandari, Allos, Safadi, Sulkaj, Sanders, Cravedi, Ghobrial, Berger and Azzi.)