Relationship between HLA alleles and cytomegalovirus infection after allogeneic hematopoietic stem cell transplant

Chen, Yolande; Rocha, Vanderson; Bittencourt, Henrique; Scieux, Catherine; Loiseau, Pascale; Esperou, Hélène; Devergié, A; Guardiola, Philippe; Socié, Gèrard; Chevret, Sylvie; Charron, Dominique; Gluckman, Éliane; Ribaud, Patricia

doi:10.1182/blood.v98.2.500

Cited by 9 publications

(5 citation statements)

References 5 publications

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“…The clinical relevance of these results is not clear. Some earlier reports have claimed that some HLA alleles, and HLA-DR15 in particular, might be associated with deficient immunity against CMV, although this was not verified later [ 16 , 34 ]. On the other hand, a higher incidence of HLA-DR15, HLA-A30, and HLA-B40 was found in a subgroup of AHSCT recipients with CMV reactivation in the absence of aGVHD [ 12 ].…”

Section: Discussionmentioning

confidence: 99%

Factors Associated with Cytomegalovirus Reactivation Following Allogeneic Hematopoietic Stem Cell Transplantation: Human Leukocyte Antigens Might Be Among the Risk Factors

Acar¹,

Akı²,

Bozdayı³

et al. 2014

Tjh

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Objective: Cytomegalovirus (CMV) is a significant cause of morbidity and mortality in allogeneic hematopoietic stem cell transplantation (AHSCT) recipients. Current practice includes prophylactic and preemptive treatment modalities, which have risks, side effects, and costs of their own. There is no established risk scoring system that applies to all patients. We aimed to investigate the risk factors for CMV reactivation in AHSCT recipients.Materials and Methods: We retrospectively analyzed the risk factors for CMV reactivation in 185 consequent AHSCT recipients transplanted between September 2003 and December 2009 at the Stem Cell Transplantation Unit of Gazi University. Besides the standard transplant-related parameters, HLA antigens were also included among the variables analyzed. Results: Despite the very high rate of donor (94.6%) and recipient (100%) seropositivity, which are the so-called major risk factors in previous reports, our reactivation rate was much lower, with a frequency of 24.9%. The underlying disease, sex, conditioning regimen, and presence of antithymocyte globulin or fludarabine in the conditioning regimen had no impact on reactivation rate. CMV reactivation was significantly more frequent in recipients with graft-versus-host disease (GVHD) compared to those without GVHD (p<0.0001). CMV reactivation was significantly more frequent (p<0.05) in patients with HLA-B14, HLA-DRB1*01, and HLA-DRB1*13 antigens and less frequent in recipients with HLA-A11 and HLA-DRB1*04 antigens (p<0.05). Conclusion: Universal risk factors/scores that apply to all transplant recipients are required for tailored prophylaxis and/or treatment strategies for CMV reactivation. Uncovering the role of genetic factors, including HLA antigens, as possible risk factors might lead the way to risk-adaptive strategies for adoptive cellular therapy and/or vaccination.

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Section: Discussionmentioning

confidence: 99%

Factors Associated with Cytomegalovirus Reactivation Following Allogeneic Hematopoietic Stem Cell Transplantation: Human Leukocyte Antigens Might Be Among the Risk Factors

Acar¹,

Akı²,

Bozdayı³

et al. 2014

Tjh

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“…DRB1*13 alleles are also associated with higher risk of HSV-2 lesions (Lekstrom-Himes et al 1999 ), while DRB1*13:02 is associated with lower risk of HSV-1 lesions (Malo and Wank 1998 ), highlighting the impact of a few residue differences on disease risk. Finally of note, while A*11 is only identified as significant in the meta-analysis in its well-defined association with decreased NPC (EBV) risk in South Asian populations (Bei et al 2010 ; Hildesheim et al 2002 ; Tang et al 2012 ; Tse et al 2009 ), it has also been found associated with KS in Italians (Goedert et al 2016 ) and HCMV reactivation in transplant patients (Chen et al 2001 ).…”

Section: Hla Alleles Associated With Herpesvirus Infection and Diseasementioning

confidence: 99%

The impact of HLA polymorphism on herpesvirus infection and disease

Palmer¹,

Norman²

2023

Immunogenetics

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Human Leukocyte Antigens (HLA) are cell surface molecules, central in coordinating innate and adaptive immune responses, that are targets of strong diversifying natural selection by pathogens. Of these pathogens, human herpesviruses have a uniquely ancient relationship with our species, where coevolution likely has reciprocating impact on HLA and viral genomic diversity. Consistent with this notion, genetic variation at multiple HLA loci is strongly associated with modulating immunity to herpesvirus infection. Here, we synthesize published genetic associations of HLA with herpesvirus infection and disease, both from case/control and genome-wide association studies. We analyze genetic associations across the eight human herpesviruses and identify HLA alleles that are associated with diverse herpesvirus-related phenotypes. We find that whereas most HLA genetic associations are virus- or disease-specific, HLA-A*01 and HLA-A*02 allotypes may be more generally associated with immune susceptibility and control, respectively, across multiple herpesviruses. Connecting genetic association data with functional corroboration, we discuss mechanisms by which diverse HLA and cognate receptor allotypes direct variable immune responses during herpesvirus infection and pathogenesis. Together, this review examines the complexity of HLA-herpesvirus interactions driven by differential T cell and Natural Killer cell immune responses.

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“…CMV infection was defined as pp65 antigenemia of 1/ 200,000 leukocytes [24] in 2 consecutive tests. CMV infection was treated with ganciclovir or foscarnet for 2-3 weeks or until a patient had 2 consecutive tests with negative results.…”

Section: Monitoring For CMV Infection and Preemptive Therapymentioning

confidence: 99%

Patterns of Cytomegalovirus Reactivation Are Associated with Distinct Evolutive Profiles of Immune Reconstitution after Allogeneic Hematopoietic Stem Cell Transplantation

et al. 2008

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T cell-mediated immunity is essential for the control of cytomegalovirus (CMV) infections in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Our aims were to identify patterns of CMV-specific immune responses associated with multiple or prolonged reactivations. We analyzed findings in 116 recipients during the course of infection or reactivation and latency. CD8(+) T cell responses were determined weekly, using HLA class I tetramers together with extended phenotypic analyses. Our results confirmed that recipients of allo-HSCT from unrelated donors were more susceptible to multiple reactivations and that the donor's CMV serological status influenced the occurrence of prolonged reactivations. We found that a lack of CMV-specific T cells after the first episode of reactivation was associated with multiple subsequent reactivations. In patients with uncontrolled reactivations, CMV-specific T cells of the late differentiation phenotype CD45RA(+)CD27(-)CD28(-) did not develop. Longitudinal evaluation of CD27 and CD45RA expression within the tetramer-positive subset could help identify patients in whom a protective immune response is developing. Evaluation of CMV-specific immune responses during the first episode of reactivation, together with extended phenotypes, could thus improve immune monitoring, especially in recipients at risk of uncontrolled viral reactivation.

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Relationship between HLA alleles and cytomegalovirus infection after allogeneic hematopoietic stem cell transplant

Cited by 9 publications

References 5 publications

Factors Associated with Cytomegalovirus Reactivation Following Allogeneic Hematopoietic Stem Cell Transplantation: Human Leukocyte Antigens Might Be Among the Risk Factors

Factors Associated with Cytomegalovirus Reactivation Following Allogeneic Hematopoietic Stem Cell Transplantation: Human Leukocyte Antigens Might Be Among the Risk Factors

The impact of HLA polymorphism on herpesvirus infection and disease

Patterns of Cytomegalovirus Reactivation Are Associated with Distinct Evolutive Profiles of Immune Reconstitution after Allogeneic Hematopoietic Stem Cell Transplantation

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