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Towards functional transplant donor matching by measurement of granzyme A and granzyme B production levels

Lookup NU author(s): Professor Anne Dickinson, Dr Xiao WangORCiD

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Abstract

Graft-versus-host disease (GvHD) can be a major complication after allogeneic stem cell transplantation (SCT) especially when donor and recipient are unrelated. The latter serious complication, together with the growing number of available unrelated stem cell donors, demand a simple in vitro assay for functional stem cell donor selection. Activated donor cytotoxic T lymphocytes (CTLs) and natural killer cells produce granzymes (Gr) that are involved in the pathogenesis of GvHD. We measured granzymes A and B (GrA and GrB) production levels in the supernatants of 96 h pretransplant mixed lymphocyte cultures (MLC) of 26 sibling and 31 unrelated patient/donor pairs by enzyme-linked immunosorbent assay (ELISA). In detail, the GrA and GrB production levels from a selected cohort of 37 potential patient/donor pairs were correlated with relative responses (RR) of MLC and with human leukocyte antigen (HLA) class II mismatches and with the development of acute GvHD in a second, consecutive cohort of 20 sibling SCT recipients. In vitro measurement of GrA and GrB production levels significantly correlated with the RR of pretransplant MLC (r=0.492, pless than or equal to0.01 and r=0.853, pless than or equal to0.01, respectively) and increased with the number of HLA class II mismatches between patient and donor. Pretransplant GrA production levels were significantly associated with the in vivo development of acute GvHD grades II-IV in patients transplanted with an HLA-identical sibling donor (pless than or equal to0.001). In conclusion, in vitro GrA and GrB production levels can be measured by a quantitative and sensitive ELISA. This novel and simple method may be used for functional selection of unrelated stem cell donors and for the identification of patients who are at risk for acute GvHD grades II-IV (C) 2004 Elsevier B.V. All rights reserved.

Publication metadata

Author(s): Kircher B, Hack CE, Dickinson AM, Wang XN, Oudshoorn M, Sachs A, Wolbink A, Niederwieser D, Eibl GJ, van Houwelingen HC, Goulmy E

Publication type: Article

Publication status: Published

Journal: Journal of Immunological Methods

Year: 2004

Volume: 293

Issue: 1-2

Pages: 51-59

ISSN (print): 0022-1759

ISSN (electronic): 1872-7905

Publisher: Elsevier BV

URL: http://dx.doi.org/10.1016/j.jim.2004.06.024

DOI: 10.1016/j.jim.2004.06.024

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