Effects of Antirejection Drugs on Innate Immune Cells After Kidney Transplantation

Abstract

Over the last decades, our understanding of adaptive immune responses to solid organ transplantation increased considerably and allowed development of immunosuppressive drugs targeting key alloreactive T cells mechanism. As a result, rates of acute rejection dropped and short-term graft survival improved significantly. However, long-term outcomes are still disappointing. Recently, increasing evidence supports that innate immune responses plays roles in allograft rejection and represents a valuable target to further improve long-term allograft survival. Innate immune cells are activated by molecules with stereotypical motifs produced during injury (i.e., damage-associated molecular patterns, DAMPS) or infection (i.e., pathogen-associated molecular patterns, PAMPs). Activated innate immune cells can exert direct pro-and anti-inflammatory effects, while also priming adaptive immune responses. These cells are activated after transplantation by multiple stimuli, including ischemia-reperfusion injury, rejection, and infections. Data from animal models of graft rejection, show that inhibition of innate immunity promotes development of tolerance. Therefore, understanding mechanisms of innate immunity is important to improve graft outcomes. This review discusses effects of currently used immunosuppressive agents on innate immune responses in kidney transplantation.

Successful recovery from severe COVID‐19 pneumonia after kidney transplantation: The interplay between immunosuppression and novel therapy including tocilizumab

“…17 The impact of long-term immunosuppression on the course of SARS-CoV-2 infection is not clear, and CNIs may play a positive role in mitigating the activation of the innate immune response and preventing the evolution of interstitial pneumonia. 18,19 We are also aware of the additional risk of infection when increasing steroid therapy, and that the appropriate treatment is a careful balance between the risk of graft loss and the risk of worsening the infection.…”

“…The impact of long‐term immunosuppression on the course of SARS‐CoV‐2 infection is not clear, and CNIs may play a positive role in mitigating the activation of the innate immune response and preventing the evolution of interstitial pneumonia 18,19 …”

Clinical outcome in solid organ transplant recipients with COVID-19: A single-center experience

“…In our experience, CNI tapering or withdrawal did not halt deterioration of respiratory failure, suggesting that its maintenance may partially prevent immune activation and the cytokine storm believed to be the driver of the most serious clinical pictures. [2][3][4] Interestingly, 2 patients with a recent liver transplant (<2 months before the infection), both treated with 2 doses of basiliximab and high-dose methylprednisolone as induction therapy, did not develop any significant symptom or radiological abnormalities. In conclusion, we did not see a higher mortality in solid organ transplant recipients with COVID-19 and comorbidities appear to play a significant role in the outcome of COVID-19 in this subpopulation, as recently suggested by others.…”

Mathematical modeling of interaction between innate and adaptive immune responses in COVID‐19 and implications for viral pathogenesis

“…A large body of research has been done on the effects of the drugs on different parts of immune response. 27,28 The goal of investigating immunosuppressive drugs is to explore their possible applications in COVID-19 disease management.…”