Anti-thymocyte globulins in kidney transplantation: focus on current indications and long-term immunological side effects

Abstract

Antithymocyte globulins (ATGs) are part of the immunosuppression arsenal currently used by clinicians to prevent or treat acute rejection in solid organ transplantation. ATG is a mixture of non-specific anti-lymphocyte immunoglobulins targeting not only T cell subsets but also several other immune and non-immune cells, rendering its precise immunoglobulin composition difficult to appreciate or to compare from one preparation to another. Furthermore, several mechanisms of action have been described. Taken together, this probably explains the efficacy and the side effects associated with this drug. Recent data suggest a long-term negative impact on allograft and patient outcomes, pointing out the need to better characterize the potential toxicity and the benefit-risk balance associated to this immunosuppressive therapy within large clinical trials.

T cell reconstitution after lymphocyte depletion features a different pattern of inhibitory receptor expression in ABO- versus HLA-incompatible kidney transplant recipients

“…Interestingly, high TIGIT expression has also being observed in allogenic hematopoietic stem cell transplantation, where it may mitigate the severity of graft-versushost disease (GVHD) [36,37]. In ABOi patients, TIGIT expression was negatively associated with cytokine production in CD4 + T cells, suggesting it could be a marker of hypofunctional, or exhausted, T cells, as described in other conditions [8,38,39]. This correlation was lost in HLAi patients, together with other positive correlations already described.…”

Update on Immunosuppression in Liver Transplantation

“…43 Antithymocyte globulin has an established role in prophylaxis and treatment of rejection in solid organ recipients, especially in cases of high immunologic risk. 44 Among LT recipients, possibilities of an ATG induction and a deescalated use of CNIs were investigated. A scheduled ATG induction followed later with CNI administration was compared with a conventional early CNI regimen.…”

“…Clinically significant side effects of ATG may include cytokine release, lymphopenia, opportunistic infections, posttransplant lymphoproliferative disease, and other malignancies. 44…”

Lack of Benefit and Potential Harm of Induction Therapy in Simultaneous Liver‐Kidney Transplants

“…Complications of r‐ATG in the short term seem to be mostly infection related (sepsis) and cardiovascular in origin . As a polyclonal lymphocyte‐depleting agent, r‐ATG causes extended periods of CD4 T cell lymphopenia and, subsequently, hastened immunosenescence, associated with a susceptibility to opportunistic infections via thymic, bone marrow, and peripheral T cell mechanisms . Additionally, infectious exposures, such as CMV, may further accelerate immunosenescence .…”

“…As a polyclonal lymphocyte‐depleting agent, r‐ATG causes extended periods of CD4 T cell lymphopenia and, subsequently, hastened immunosenescence, associated with a susceptibility to opportunistic infections via thymic, bone marrow, and peripheral T cell mechanisms . Additionally, infectious exposures, such as CMV, may further accelerate immunosenescence . In a United States Renal Data System analysis of over 73,000 KTA recipients reported by Meier‐Kriesche et al, r‐ATG was associated with an almost 8% increased risk of deaths related to infections when compared with no induction .…”