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Possible role of minor h antigens in the persistence of donor chimerism after stem cell transplantation; relevance for sustained leukemia remission

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Possible role of minor h antigens in the persistence of donor chimerism after stem cell transplantation; relevance for sustained leukemia remission. / van der Torren, Cornelis R; van Hensbergen, Yvette; Luther, Susanne; Aghai, Zohara; Rychnavská, Zuzana Stachová; Slot, Manon; Scherjon, Sicco; Kröger, Nicolaus; Ganser, Arnold; Weissinger, Eva M; Goulmy, Els; Hambach, Lothar.

In: PLOS ONE, Vol. 10, No. 3, 01.01.2015, p. e0119595.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

van der Torren, CR, van Hensbergen, Y, Luther, S, Aghai, Z, Rychnavská, ZS, Slot, M, Scherjon, S, Kröger, N, Ganser, A, Weissinger, EM, Goulmy, E & Hambach, L 2015, 'Possible role of minor h antigens in the persistence of donor chimerism after stem cell transplantation; relevance for sustained leukemia remission', PLOS ONE, vol. 10, no. 3, pp. e0119595. https://doi.org/10.1371/journal.pone.0119595

APA

van der Torren, C. R., van Hensbergen, Y., Luther, S., Aghai, Z., Rychnavská, Z. S., Slot, M., Scherjon, S., Kröger, N., Ganser, A., Weissinger, E. M., Goulmy, E., & Hambach, L. (2015). Possible role of minor h antigens in the persistence of donor chimerism after stem cell transplantation; relevance for sustained leukemia remission. PLOS ONE, 10(3), e0119595. https://doi.org/10.1371/journal.pone.0119595

Vancouver

van der Torren CR, van Hensbergen Y, Luther S, Aghai Z, Rychnavská ZS, Slot M et al. Possible role of minor h antigens in the persistence of donor chimerism after stem cell transplantation; relevance for sustained leukemia remission. PLOS ONE. 2015 Jan 1;10(3):e0119595. https://doi.org/10.1371/journal.pone.0119595

Bibtex

@article{ca4f9a3b857f4c9aa0ee14bce5681068,
title = "Possible role of minor h antigens in the persistence of donor chimerism after stem cell transplantation; relevance for sustained leukemia remission",
abstract = "Persistent complete donor chimerism is an important clinical indicator for remissions of hematological malignancies after HLA-matched allogeneic stem cell transplantation (SCT). However, the mechanisms mediating the persistence of complete donor chimerism are poorly understood. The frequent coincidence of complete donor chimerism with graft-versus-leukemia effects and graft-versus-host disease suggests that immune responses against minor histocompatibility antigens (mHags) are playing an important role in suppressing the host hematopoiesis after allogeneic SCT. Here, we investigated a possible relationship between donor immune responses against the hematopoiesis-restricted mHag HA-1 and the long-term kinetics of host hematopoietic chimerism in a cohort of 10 patients after allogeneic HLA-matched, HA-1 mismatched SCT. Functional HA-1 specific CTLs (HA-1 CTLs) were detectable in 6/10 patients lysing host-type hematopoietic cells in vitro. Presence of HA-1 CTLs in the peripheral blood coincided with low host hematopoiesis levels quantified by highly sensitive mHag specific PCR. Additionally, co-incubation of host type CD34+ cells with HA-1 CTLs isolated after allogeneic SCT prevented progenitor and cobblestone area forming cell growth in vitro and human hematopoietic engraftment in immunodeficient mice. Conversely, absence or loss of HA-1 CTLs mostly coincided with high host hematopoiesis levels and/or relapse. In summary, in this first study, presence of HA-1 CTLs paralleled low host hematopoiesis levels. This coincidence might be supported by the capacity of HA-1 CTLs isolated after allogeneic SCT to specifically eliminate host type hematopoietic stem/progenitor cells. Additional studies involving multiple mismatched mHags in more patients are required to confirm this novel characteristic of mHag CTLs as factor for the persistence of complete donor chimerism and leukemia remission after allogeneic SCT.",
author = "{van der Torren}, {Cornelis R} and {van Hensbergen}, Yvette and Susanne Luther and Zohara Aghai and Rychnavsk{\'a}, {Zuzana Stachov{\'a}} and Manon Slot and Sicco Scherjon and Nicolaus Kr{\"o}ger and Arnold Ganser and Weissinger, {Eva M} and Els Goulmy and Lothar Hambach",
year = "2015",
month = jan,
day = "1",
doi = "10.1371/journal.pone.0119595",
language = "English",
volume = "10",
pages = "e0119595",
journal = "PLOS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "3",

}

RIS

TY - JOUR

T1 - Possible role of minor h antigens in the persistence of donor chimerism after stem cell transplantation; relevance for sustained leukemia remission

AU - van der Torren, Cornelis R

AU - van Hensbergen, Yvette

AU - Luther, Susanne

AU - Aghai, Zohara

AU - Rychnavská, Zuzana Stachová

AU - Slot, Manon

AU - Scherjon, Sicco

AU - Kröger, Nicolaus

AU - Ganser, Arnold

AU - Weissinger, Eva M

AU - Goulmy, Els

AU - Hambach, Lothar

PY - 2015/1/1

Y1 - 2015/1/1

N2 - Persistent complete donor chimerism is an important clinical indicator for remissions of hematological malignancies after HLA-matched allogeneic stem cell transplantation (SCT). However, the mechanisms mediating the persistence of complete donor chimerism are poorly understood. The frequent coincidence of complete donor chimerism with graft-versus-leukemia effects and graft-versus-host disease suggests that immune responses against minor histocompatibility antigens (mHags) are playing an important role in suppressing the host hematopoiesis after allogeneic SCT. Here, we investigated a possible relationship between donor immune responses against the hematopoiesis-restricted mHag HA-1 and the long-term kinetics of host hematopoietic chimerism in a cohort of 10 patients after allogeneic HLA-matched, HA-1 mismatched SCT. Functional HA-1 specific CTLs (HA-1 CTLs) were detectable in 6/10 patients lysing host-type hematopoietic cells in vitro. Presence of HA-1 CTLs in the peripheral blood coincided with low host hematopoiesis levels quantified by highly sensitive mHag specific PCR. Additionally, co-incubation of host type CD34+ cells with HA-1 CTLs isolated after allogeneic SCT prevented progenitor and cobblestone area forming cell growth in vitro and human hematopoietic engraftment in immunodeficient mice. Conversely, absence or loss of HA-1 CTLs mostly coincided with high host hematopoiesis levels and/or relapse. In summary, in this first study, presence of HA-1 CTLs paralleled low host hematopoiesis levels. This coincidence might be supported by the capacity of HA-1 CTLs isolated after allogeneic SCT to specifically eliminate host type hematopoietic stem/progenitor cells. Additional studies involving multiple mismatched mHags in more patients are required to confirm this novel characteristic of mHag CTLs as factor for the persistence of complete donor chimerism and leukemia remission after allogeneic SCT.

AB - Persistent complete donor chimerism is an important clinical indicator for remissions of hematological malignancies after HLA-matched allogeneic stem cell transplantation (SCT). However, the mechanisms mediating the persistence of complete donor chimerism are poorly understood. The frequent coincidence of complete donor chimerism with graft-versus-leukemia effects and graft-versus-host disease suggests that immune responses against minor histocompatibility antigens (mHags) are playing an important role in suppressing the host hematopoiesis after allogeneic SCT. Here, we investigated a possible relationship between donor immune responses against the hematopoiesis-restricted mHag HA-1 and the long-term kinetics of host hematopoietic chimerism in a cohort of 10 patients after allogeneic HLA-matched, HA-1 mismatched SCT. Functional HA-1 specific CTLs (HA-1 CTLs) were detectable in 6/10 patients lysing host-type hematopoietic cells in vitro. Presence of HA-1 CTLs in the peripheral blood coincided with low host hematopoiesis levels quantified by highly sensitive mHag specific PCR. Additionally, co-incubation of host type CD34+ cells with HA-1 CTLs isolated after allogeneic SCT prevented progenitor and cobblestone area forming cell growth in vitro and human hematopoietic engraftment in immunodeficient mice. Conversely, absence or loss of HA-1 CTLs mostly coincided with high host hematopoiesis levels and/or relapse. In summary, in this first study, presence of HA-1 CTLs paralleled low host hematopoiesis levels. This coincidence might be supported by the capacity of HA-1 CTLs isolated after allogeneic SCT to specifically eliminate host type hematopoietic stem/progenitor cells. Additional studies involving multiple mismatched mHags in more patients are required to confirm this novel characteristic of mHag CTLs as factor for the persistence of complete donor chimerism and leukemia remission after allogeneic SCT.

U2 - 10.1371/journal.pone.0119595

DO - 10.1371/journal.pone.0119595

M3 - SCORING: Journal article

C2 - 25774796

VL - 10

SP - e0119595

JO - PLOS ONE

JF - PLOS ONE

SN - 1932-6203

IS - 3

ER -