Clinical relevance of the minor histocompatibility antigen HA-1 in allogeneic bone marrow transplantation between HLA identical siblings

Tait, Brian D.; Maddison, Rebecca; McCluskey, James; Deayton, Sue; Heatley, Sue L.; Lester, Susan; Bardy, Peter; Szer, Jeff; Grigg, Andrew; Spencer, Andrew; Schwarer, Anthony P.; Holdsworth, Rhonda

doi:10.1016/s0041-1345(00)02816-5

Cited by 12 publications

(6 citation statements)

References 8 publications

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“…Others described increased incidence of cGVHD in the case of mismatched autosomal MiHAs localized on hematopoietic cells: HA-1, HA-2, and HA-8 [15, 16, 23, 65]. There are also reports that report no impact of autosomal MiHAs on GVHD [49, 66]. …”

Section: Discussionmentioning

confidence: 99%

Occurrence and Impact of Minor Histocompatibility Antigens' Disparities on Outcomes of Hematopoietic Stem Cell Transplantation from HLA-Matched Sibling Donors

Dzierżak‐Mietła

Markiewicz

Siekiera³

et al. 2012

Bone Marrow Research

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We have examined the alleles of eleven minor histocompatibility antigens (MiHAs) and investigated the occurrence of immunogenic MiHA disparities in 62 recipients of allogeneic hematopoietic cell transplantation (allo-HCT) with myeloablative conditioning performed between 2000 and 2008 and in their HLA-matched sibling donors. Immunogenic MiHA mismatches were detected in 42 donor-recipient pairs: in 29% MiHA was mismatched in HVG direction, in another 29% in GVH direction; bidirectional MiHA disparity was detected in 10% and no MiHA mismatches in 32%. Patients with GVH-directed HY mismatches had lower both overall survival and disease-free survival at 3 years than patients with compatible HY; also higher incidence of both severe acute GvHD and extensive chronic GVHD was observed in patients with GVH-directed HY mismatch. On contrary, GVH-directed mismatches of autosomally encoded MiHAs had no negative effect on overall survival. Results of our study help to understand why posttransplant courses of allo-HCT from siblings may vary despite the complete high-resolution HLA matching of a donor and a recipient.

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Section: Discussionmentioning

confidence: 99%

Occurrence and Impact of Minor Histocompatibility Antigens' Disparities on Outcomes of Hematopoietic Stem Cell Transplantation from HLA-Matched Sibling Donors

Dzierżak‐Mietła

Markiewicz

Siekiera³

et al. 2012

Bone Marrow Research

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“…A similar effect on GVHD was also reported earlier for mHAs present solely on hematopoietic cells, such as HA-1, 4,23-26 HA-2 23 and HA-8, 27 although it was not confirmed by others. [28][29][30][31] We have observed only a trend toward more frequent cGVHD in the presence of GVH-directed immunogenic disparities of mHAs with restricted tissue distribution. Moreover, when HA-1 mismatch was directed oppositely (in HVG direction), cGVHD tended to occur less frequently.…”

Section: Presence Of Mha Disparitiesmentioning

confidence: 99%

Immunogenic disparities of 11 minor histocompatibility antigens (mHAs) in HLA-matched unrelated allogeneic hematopoietic SCT

Markiewicz

Siekiera²,

Karolczyk

et al. 2008

Bone Marrow Transplant

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We determined the alleles of 11 mHAs and investigated the association of immunogenic mHA mismatches between a donor and a recipient with a course of allogeneic hematopoietic SCT (allo-HSCT) from 10/10 alleles HLA-matched unrelated donors in 92 recipients after myeloablative conditioning between 2004 and 2006. The frequency analysis of mHA alleles, genotypes and phenotypes accompanied by appropriate restriction HLA Ags allowed for an estimation of the probability of immunogenic mismatches, which was the highest for HA-1, HA-8 and HY. GVH-directed disparity of mHAs with broad tissue distribution, especially of the sex-related HY Ag, influenced the results of allo-HSCT from HLAmatched unrelated donors by not only increasing the probability of chronic GVHD (cGVHD) but also by decreasing the relapse rate.

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“…31 However, this finding has not been consistently seen, with subsequent studies observing both similar [32][33][34] and conflicting results. [35][36][37] HA-1-specific CTLs have been demonstrated in the peripheral blood of HSCT recipients as early as 14 days after transplantation with significantly increased levels during acute GVHD. 38 A study of 3 patients treated with donor lymphocyte infusion (DLI) for hematologic malignancy after allogeneic HSCT showed that a high percentage of the leukemia-reactive T cells in the recipients were directed against HA-1 or HA-2.…”

Section: Minor Histocompatibility Antigensmentioning

confidence: 99%

Beyond HLA: the significance of genomic variation for allogeneic hematopoietic stem cell transplantation

Mullally

Ritz

2006

Blood

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The last 2 years have seen much excitement in the field of genetics with the identification of a formerly unappreciated level of "structural variation" within the normal human genome. Genetic structural variants include deletions, duplications, and inversions in addition to the recently discovered, copy number variants. Single nucleotide polymorphisms are the most extensively evaluated variant within the genome to date. Combining our knowledge from these studies with our rapidly accumulating understanding of structural variants, it is apparent that the extent of genetic dissimilarity between any 2 individuals is considerable and much greater than that which was previously recognized. Clearly, this more diverse view of the genome has significant implications for allogeneic hematopoietic stem cell transplantation, not least in the generation of transplant antigens but also in terms of individual susceptibility to transplant-related toxicities. With advances in DNA sequencing technology we now have the capacity to perform genome-wide analysis in a high throughput fashion, permitting a detailed genetic analysis of patient and donor prior to transplantation. Understanding the significance of this additional genetic information and applying it in a clinically meaningful way will be one of the challenges faced by transplant clinicians in the future. Introduction Structural variation in the human genomeRecently, much focus has been directed at documenting the extent of normal human genomic variation, particularly in the form of single nucleotide polymorphisms (SNPs; Table 1). In October 2005, phase 1 of the International Hapmap Project was published. 2 This project catalogued more than one million SNPs, genomewide, into a publicly accessible database (www.hapmap.org). Approximately 11 500 of the SNPs recorded in phase 1 are nonsynonymous coding SNPs. Other examples of genomic variation include gene deletions, inverted gene sequences, multiple copy gene duplications, segmental duplications and large-scale copy number variants (CNVs). Each of these structural variants is shown schematically in Figure 1.In the year prior to the Hapmap publication, 2 landmark studies reported that large-scale CNVs are distributed widely throughout the human genome and that a high proportion of these encompass known genes. 3,4 These studies were groundbreaking because they challenged the previously held view that the complete DNA sequences of any 2 individuals are 99.9% identical, the 0.1% difference being largely attributed to SNPs. Subsequently, several studies on CNVs followed, 5-7 culminating in a large international study of the Hapmap population by Redon et al 101 that identified more than 1400 CNVs spanning approximately 12% of the human genome. Even with this comprehensive evaluation, it is likely that this present index of CNVs is far from complete and new variants are continually being discovered. 8 In 2006, 3 studies specifically characterized deletion variants in the human genome. 9-11 Combined, these investigations described ap...

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Clinical relevance of the minor histocompatibility antigen HA-1 in allogeneic bone marrow transplantation between HLA identical siblings

Cited by 12 publications

References 8 publications

Occurrence and Impact of Minor Histocompatibility Antigens' Disparities on Outcomes of Hematopoietic Stem Cell Transplantation from HLA-Matched Sibling Donors

Occurrence and Impact of Minor Histocompatibility Antigens' Disparities on Outcomes of Hematopoietic Stem Cell Transplantation from HLA-Matched Sibling Donors

Immunogenic disparities of 11 minor histocompatibility antigens (mHAs) in HLA-matched unrelated allogeneic hematopoietic SCT

Beyond HLA: the significance of genomic variation for allogeneic hematopoietic stem cell transplantation

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