Mismatches of Minor Histocompatibility Antigens between HLA-Identical Donors and Recipients and the Development of Graft-Versus-Host Disease after Bone Marrow Transplantation

Goulmy, Els; Schipper, R.F.; Pool, J.; Blokland, E.; Falkenburg, J.H. Frederik; Vossen, Jaak M.; Gratwohl, Aloïs; Vogelsang, G. B.; Houwelingen, Hans C. van; Rood, Jon J. van

doi:10.1056/nejm199602013340501

Cited by 567 publications

(355 citation statements)

References 20 publications

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“…Nevertheless, it has long been established that alloreactivity against MHC molecules is not the only factor conditioning GVHD since the 1-3% occurrence of DR/DQ and DP recombination cannot account for the 20-50% of GVHD reported between genotypically identical siblings (1). Moreover, the contribution of minor histocompatibility antigens to the increased risk of GVHD has been recently demonstrated (19). Because minor histocompatibility antigens disparity is bound to be significantly greater between unrelated than between genoidentical individuals (20), it is likely that specific T cells directed against minor antigens also contribute to the increased risk of GVHD after unrelated bone marrow transplantation.…”

Section: Discussionmentioning

confidence: 99%

Acute graft versus host disease due to T lymphocytes recognizing a single HLA-DPB1*0501 mismatch.

Gaschet¹,

Lim²,

Liem³

et al. 1996

J. Clin. Invest.

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Analysis of a large number of unrelated bone marrow transplantations (BMT) has shown that HLA-DP incompatibility did not detectably influence the risk for acute graft-versushost disease (aGVHD). Accordingly, it was proposed that HLA-DP determinants did not function as transplantation antigens in the same way as HLA-A, -B, or -DR. We have previously shown that HLA-DP (as well as HLA-A, -B, -DQ, or -DR)-specific T cells could be isolated from skin biopsies of patients who developed an aGVHD after semiallogeneic BMT. Nevertheless, whether a single HLA-DP mismatched allele could induce a detectable allo-specific reaction in vivo after BMT remained to be established. To directly address this issue we studied one patient who presented aGVHD after receiving purified CD34 ϩ bone marrow (BM) cells from an unrelated donor with a single HLA-DP mismatch in the GVHD direction. To characterize the immunological events associated with GVHD, we analyzed the peripheral T cell repertoire, the T cell receptor V ␤ diversity, and the specificity of T cells invading a skin biopsy at the onset of GVHD. Our results demonstrated that a large fraction of skin-infiltrating lymphocytes, which expressed diverse T cell receptors, were reactive against this single HLA-DPB1*0501 mismatch and consequently that a single HLA-DP mismatch between BM donor and recipient can activate a strong T cell response in vivo. ( J. Clin. Invest. 1996. 98:100-107.)

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Section: Discussionmentioning

confidence: 99%

Acute graft versus host disease due to T lymphocytes recognizing a single HLA-DPB1*0501 mismatch.

Gaschet¹,

Lim²,

Liem³

et al. 1996

J. Clin. Invest.

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“…7 In BMT that are MHC matched but mHA disparate, donor T cells still recognize MHC peptide derived from the products of recipient polymorphic genes, the mHAs. [8][9][10] The expression of mHAs is wide and variable. Thus, different mHAs might dictate variable phenotype, target organ involvement, development kinetics of GVHD and antitumor responses after allogeneic BMT.…”

Section: Triggers For Induction Of Gvhdmentioning

confidence: 99%

New perspectives on the biology of acute GVHD

Paczesny

Hanauer

Sun

et al. 2009

Bone Marrow Transplant

157

126

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The use of allogeneic hematopoietic cell transplantation (HCT) has increased as new techniques have been developed for transplantation in patients who previously would not have been considered HCT candidates. However, its efficacy continued to be limited by the development of frequent and severe acute GVHD. The complex and intricate pathophysiology of acute GVHD is a consequence of interactions between the donor and host innate and adaptive immune responses. Multiple inflammatory molecules and cell types are implicated in the development of GVHD that can be categorized as:(1) triggers that initiate GVHD by therapy-induced tissue damage and the antigen disparities between host and graft tissue; (2) sensors that detect the triggers, that is, process and present alloantigens; (3) mediators such as T-cell subsets (naive, memory, regulatory, Th17 and natural killer T cells) and (4) the effectors and amplifiers that cause damage of the target organs. These multiple inflammatory molecules and cell types that are implicated in the development of GVHD have been described with models that use stepwise cascades. Herein, we provide a novel perspective on the immunobiology of acute GVHD and briefly discuss some of the outstanding questions and limitations of the model systems.

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“…However, these findings do not necessarily imply a role for these MiHAs in GVHD, because host reactive anti-MiHAs CTLs were found with similar frequencies in patients with or without GVHD (35). Goulmy et al have recently reported that a mismatch of HA-1 MiHA, whose molecular structure is unknown, was associated with an increased rate of GVHD in adult recipients of bone marrow transplants (36). Thus, HA-1 is heretofore the only MiHA that has been implicated in GVHD.…”

Section: Discussionmentioning

confidence: 99%

Identification of an immunodominant mouse minor histocompatibility antigen (MiHA). T cell response to a single dominant MiHA causes graft-versus-host disease.

Perreault

Jutras²,

Roy³

et al. 1996

J. Clin. Invest.

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Mismatches of Minor Histocompatibility Antigens between HLA-Identical Donors and Recipients and the Development of Graft-Versus-Host Disease after Bone Marrow Transplantation

Abstract: A mismatch of minor histocompatibility antigen HA-1 can cause GVHD in adult recipients of allogeneic bone marrow from HLA-identical donors. Prospective HA-1 typing may improve donor selection and identify recipients who are at high risk for GVHD.

Cited by 567 publications

References 20 publications

Acute graft versus host disease due to T lymphocytes recognizing a single HLA-DPB1*0501 mismatch.

Acute graft versus host disease due to T lymphocytes recognizing a single HLA-DPB1*0501 mismatch.

New perspectives on the biology of acute GVHD

Identification of an immunodominant mouse minor histocompatibility antigen (MiHA). T cell response to a single dominant MiHA causes graft-versus-host disease.

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