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Pediatric Transplants

IgG antibodies to ATG early after pediatric hematopoietic SCT increase the risk of acute GVHD

Bone Marrow Transplantation volume 47, pages 360–368 (2012)Cite this article

Abstract

Anti-thymocyte globulin (ATG), raised in rabbits, is frequently used in allogeneic hematopoietic SCT (HSCT), to prevent graft rejection and acute GVHD. In solid organ transplant patients, antibodies to rabbit IgG result in an enhanced clearance of ATG. The occurrence of such antibodies in HSCT recipients and their clinical impact is unknown. Concentrations of ATG and anti-ATG antibodies were measured in 72 pediatric HSCT recipients treated with ATG as part of the conditioning. Anti-ATG antibodies were detected in 20 children (28%), all transplanted with a non-depleted graft. IgG anti-ATG, alone or combined with IgM and/or IgA anti-ATG, appeared in 10 children. Four patients developed IgG anti-ATG antibodies early (before day 22) post-HSCT. They had steep drops in ATG levels and showed rapid T-cell recovery, which was associated with a significantly increased risk of acute GVHD. In six patients IgG anti-ATG responses occurred later (range 28–46 days) after HSCT without an increased risk of GVHD. A total of 10 children only mounted an IgM (and IgA) anti-ATG response, which was without major impact on ATG levels. These results indicate that early development of IgG anti-ATG antibodies has a major impact on acute GVHD. Routine analysis ATG/anti-ATG Ab measurement should be considered.

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Acknowledgements

We thank the medical and nursing staff of the pediatric transplant unit for implementing this study protocol, JLM Waaijer for her assistance in the management and sampling of patients, H Putter from the medical statistics department for advice, A van Strien for performing a literature study, and AGS van Halteren and MW Schilham for critically reading the manuscript.

Author contributions: CJvdZ designed and performed the study and prepared the manuscript, RB and MvT designed the study and prepared the manuscript, AJ-H and SR performed the measurements, RE and AL participated in interpretation of data and finalizing the manuscript.

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  1. C M Jol-van der Zijde and R G M Bredius: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Pediatric Stem Cell Transplantation, Leiden University Medical Center (LUMC), Leiden, The Netherlands

    C M Jol-van der Zijde, R G M Bredius, A M Jansen-Hoogendijk, S Raaijmakers, R M Egeler, A C Lankester & M J D van Tol

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  1. C M Jol-van der Zijde
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Correspondence to C M Jol-van der Zijde.

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Jol-van der Zijde, C., Bredius, R., Jansen-Hoogendijk, A. et al. IgG antibodies to ATG early after pediatric hematopoietic SCT increase the risk of acute GVHD. Bone Marrow Transplant 47, 360–368 (2012). https://doi.org/10.1038/bmt.2011.166

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