Anti-thymocyte globulins capable of binding to T and B cells reduce graft-vs-host disease without increasing relapse

Abstract

Anti-thymocyte globulin (ATG) is polyclonal, containing Ab specificities capable of binding to various immune-cell subsets implicated in the pathogenesis of GVHD, including T cells, B cells, natural killer cells, monocytes/macrophages, neutrophils and DC. We wished to determine which ATG specificities are important for GVHD prevention. We measured day 7 serum levels of 23 ATG specificities in 120 hematopoietic cell transplant recipients whose myeloablative conditioning included 4.5 mg/kg ATG (thymoglobulin). High levels of ATG specificities capable of binding to T-and B-cell subsets were associated with a low likelihood of acute GVHD (aGVHD). High levels of these ATG specificities were associated with increased rates of viral but not bacterial or fungal infections. They were not associated with an increased risk of malignancy relapse; on the contrary, high levels of ATG specificities capable of binding to regulatory T cells and invariant NKT cells were associated with a low risk of relapse. In conclusion, high levels of ATG antibodies to Ag(s) expressed on T and B cells are associated with a low risk of aGVHD and a high risk of viral but not bacterial or fungal infections. These antibodies have neutral or beneficial effects on relapse.

Impact of Serotherapy on Immune Reconstitution and Survival Outcomes After Stem Cell Transplantations in Children: Thymoglobulin Versus Alemtuzumab

“…Alemtuzumab is a humanized monoclonal antibody specific for CD52. In the HSCT setting, both types of serotherapy are used to eliminate T cells, but they also target other cell types, eg, B cells and natural killer (NK) cells [6][7][8][9][10]. ATG and alemtuzumab are considered instrumental in reducing the risk of rejection by suppressing the reaction of host T cells against the graft.…”

ABO, alemtuzumab and allogeneic transplantation

“…ATG does contain antibodies reactive with NKT cells, including iNKT cells, although activity appears to be weak based on antibody clearance. 17 In mice and humans, ATG leads to only mild decreases in iNKT cells (9%) compared with other lymphocyte populations, leading to a 200-fold relative increase in circulating iNKT cells. 18 As a consequence, there is increasing interest in the use of alemtuzumab over ATG in ABO-mismatched solid organ transplantation, with encouraging results.…”

IL15 levels on day 7 after hematopoietic cell transplantation predict chronic GVHD

“…As high ATG and high IL15 levels appear to have both anti-GVHD and pro-viral effects 16,32 (see Results), the homeostatic production of IL15 may be stimulated by low numbers of both alloreactive and antiviral CD8 T cells.…”

“…Prophylaxis of cGVHD using T-cell depletion ex vivo (for example, by graft enrichment for CD34 cells) or in vivo (for example, using alemtuzumab or polyclonal anti-T-cell antibodies like rabbit antithymocyte globulin (ATG)) is more efficacious than treatment. [9][10][11][12][13][14][15] However, the prophylaxis has side effects (for example, viral infections 16 ). Therefore, it would be desirable to give prophylaxis or preemptive therapy only to patients at high risk of developing cGVHD.…”