0000000000082195
AUTHOR
Joannis Mytilineos
showing 16 related works from this author
P046 Deconstructing HLA-C mismatch in hematopoietic stem cell transplantation
2016
Contrary to other HLA loci, allele vs antigen mismatches in HLA-C appear to differentially impact HSCT outcome. Aim of this study was to investigate the independent role of other factors characterizing a patient’s HLA-C non-shared allele, in HSCT outcome as well as their distribution in allele vs antigen mismatched cases. 288 9/10 HLA-C mismatched unrelated transplant pairs, were additionally genotyped by sequence based typing for rs9264942(C/T) and rs67384697(ins/del), which are considered surrogate markers of HLA-C expression levels. A proxy MFI model as previously described (Petersdorf et al., Blood 2014), was also implemented in the analysis. All patient non-shared alleles were characte…
Donors with KIR-Bx Haplotypes Improve Outcome of Unrelated Hematopoietic Stem Cell Transplantation for Recipients with a Myeloid Malignant Disease an…
2015
relapse, or transplant related mortality (TRM) (p1⁄40.2, p1⁄40.1, p1⁄40.08, respectively). To investigate why higher CPSS scores were associated with higher mortality, we performed analysis restricted to patients with relapse following HCT. Those with intermediate-2/high riskhadnearly two-fold increase in riskof death after relapse compared to thosewith low/intermediate1 CPSS scores. Corresponding rates for low/intermediate-1 risk groups,OSat1year, 3years, and5yearswere61%,48%, and44% respectivelyand for intermediate-2/high riskgroupswere 38%, 32%, and19%respectively.OSofpatientswho receivedpre-HCT treatment with hypomethylating agents, chemotherapy, or both was not different compared to th…
P043 HLA-DPB matching and donor cytomegalovirus positive (CMV+) status: An “unconventional alliance” associated with a decreased relapse incidence in…
2017
Aim While the role of HLA-DPB1 (DP) compatibility in uHSCT regarding graft versus host disease (GVHD)- and graft versus leukaemia (GVL)-effects has been extensively discussed, its interaction with donor CMV status (dCMV), remains elusive. The aim of this study was, to investigate the impact of dCMV status in DP matched (DPM) and mismatched (DPMM) uHSCT. Methods 1749 HSCT transplant (Tx) pairs were DP genotyped with an exon 2 amplicon based NGS approach in order to assess their DP matching status. CMV sero-status as well as clinical data were retrieved from the German Stem Cell Registry. Overall survival (OS), relapse incidence (RI) and chronic GvHD (cGvHD) were defined as endpoints, while s…
16thIHIW: Anti-HLA alloantibodies of the of IgA isotype in re-transplant candidates
2012
Summary In this multicentre study, sera from 803 retransplant candidates, including 775 kidney transplant recipients, were analysed with regard to the presence and specificity of anti-HLA alloantibodies of the IgA isotype using a modified microsphere-based platform. Of the kidney recipients, nearly one-third (n = 237, 31%) had IgA alloantibodies. Mostly, these antibodies were found in sera that also harboured IgG alloantibodies that could be found in a total of 572 (74%) of patients. Interestingly, IgA anti-HLA antibodies were preferentially targeting HLA class I antigens in contrast to those of the IgG isotype, which targeted mostly both HLA class I and II antigens. Donor specificity of th…
Relative Impact of HLA Matching and Non-HLA Donor Characteristics on Outcomes of Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia and …
2018
Increasing donor-recipient HLA disparity is associated with negative outcomes of allogeneic hematopoietic stem cell transplantation (HSCT), but its comparative relevance amid non-HLA donor characteristics is not well established. We addressed this question in 3215 HSCTs performed between 2005 and 2013 in Germany for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Donors were HLA-matched related (MRD; n = 872) or unrelated (10/10 MUD, n = 1553) or HLA-mismatched unrelated (10/10 MMUD, n = 790). Overall survival (OS) was similar after MRD compared with 10/10 MUD HSCT, reflecting opposing hazards of relapse (hazard ratio [HR], 1.32; P.002) and nonrelapse mortality (HR, .63; P.0…
Association between human papillomavirus 16 E6 variants and human leukocyte antigen class I polymorphism in cervical cancer of Swedish women.
2003
Abstract Persistent infection with human papillomavirus (HPV), particularly HPV16, represents the prime risk factor in cervical carcinogenesis. HPV variants ( e.g. , within the E6 gene) together with immunogenetic factors of the host may be responsible either for effective viral clearance, or alternatively, for viral persistence. Peripheral blood from 27 HPV16 positive Swedish women with cervical carcinoma, who had previously been tested for HPV16 E6 variants, was used for human leukocyte antigen (HLA) class I typing. Women with HLA-B*44, HLA-B*51, or HLA-B*57 who were infected with the HPV16 E6 variant L83V had an approximately four- to fivefold increased risk for cancer compared with cont…
The Human Leukocyte Antigen-DPB1 Degree of Compatibility Is Determined by Its Expression Level and Mismatch Permissiveness: A German Multicenter Anal…
2021
T-cell epitope matching according to the TCE3 algorithm classifies HLA-DPB1 mismatches in permissive and non-permissive. This classification has been shown to be predictive for mortality and acute GvHD (aGvHD) events in large international cohorts. We retrospectively genotyped HLA-DPB1 in 3523 patients transplanted in Germany between 2000 and 2014 and in their unrelated donors using an Illumina amplicon-NGS based assay. Aim of the study was to evaluate DP-compatibility beyond the established TCE3 algorithm by assessing the combined effect of several DP-mismatch parameters on post-transplant outcome. We implemented an extended DP-mismatch assessment model where TCE3, DP allotype expression w…
High-resolution HLA matching in hematopoietic stem cell transplantation: a retrospective collaborative analysis.
2013
To validate current donor selection strategies based on previous international studies, we retrospectively analyzed 2646 transplantations performed for hematologic malignancies in 28 German transplant centers. Donors and recipients were high resolution typed for HLA-A, -B, -C, -DRB1, and -DQB1. The highest mortality in overall survival analysis was seen for HLA-A, -B, and DRB1 mismatches. HLA-DQB1 mismatched cases showed a trend toward higher mortality, mostly due to HLA-DQB1 antigen disparities. HLA incompatibilities at >1 locus showed additive detrimental effects. HLA mismatching had no significant effect on relapse incidence and primary graft failure. Graft source had no impact on surviv…
MICA-129 Dimorphism and Soluble MICA Are Associated With the Progression of Multiple Myeloma
2018
Natural killer (NK) cells are immune innate effectors playing a pivotal role in the immunosurveillance of multiple myeloma (MM) since they are able to directly recognize and kill MM cells. In this regard, among activating receptors expressed by NK cells, NKG2D represents an important receptor for the recognition of MM cells, being its ligands expressed by tumor cells, and being able to trigger NK cell cytotoxicity. The MHC class I-related molecule A (MICA) is one of the NKG2D ligands; it is encoded by highly polymorphic genes and exists as membrane-bound and soluble isoforms. Soluble MICA (sMICA) is overexpressed in the serum of MM patients, and its levels correlate with tumor progression. …
OR26. Investigating the impact of patient’s non-shared HLA-C Allotype expression levels in A 9/10 Single HLA-C mismatched hematopoieticstem cell tran…
2018
Aim Petersdorf et al. reported in 2014 an association between patient high expressed HLA-C (C) allotypes and inferior HSCT outcome using an imputed C-expression model (Apps et al., 2013). This study aims at: a) examining the validity of Apps et al. model in Caucasians by using the same methodology in a sample of 400 healthy German blood donors. b) specifically investigating the effect of patient’s non-shared (PNS) C expression levels on outcome by applying C expression imputed data in a 9/10 HLA C-mismatched HSCT setting. Methods Buffy coats from 400 healthy German blood donors were tested by flow cytometry as previously described (Apps et al., 2013) in order to determine C expression on ly…
Impact of Donor Activating KIR Genes on HSCT Outcome in C1-Ligand Negative Myeloid Disease Patients Transplanted with Unrelated Donors-A Retrospectiv…
2017
Natural Killer cells (NK) are lymphocytes with the potential to recognize and lyse cells which escaped T-cell mediated lysis due to their aberrant HLA expression profiles. Killer cell immunoglobulin-like receptors (KIR) influence NK-cell activity by mediation of activating or inhibitory signals upon interaction with HLA-C (C1, C2) ligands. Therefore, absence of ligands for donor inhibitory KIRs following hematopoietic stem cell transplantation (HSCT) may have an influence on its outcome. Previous studies showed that C1 negative patients have a decreased HSCT outcome. Our study, based on a cohort of 200 C1-negative patients, confirmed these findings for the endpoints: overall survival (OS: H…
Increased age-associated mortality risk in HLA-mismatched hematopoietic stem cell transplantation.
2016
We investigated a possible interaction between age-associated risk and HLA-mismatch associated risk on prognosis in different age categories of recipients of unrelated hematopoietic stem cell transplants (HSCT) (n=3019). Patients over 55 years of age transplanted with 8/10 donors showed a mortality risk of 2.27 (CI 1.70–3.03, P<0.001) and 3.48 (CI 2.49–4.86, P<0.001) when compared to 10/10 matched patients in the same age group and to 10/10 matched patients aged 18–35 years, respectively. Compared to 10/10 matched transplantations within each age category, the Hazards Ratio for 8/10 matched transplantation was 1.14, 1.40 and 2.27 in patients aged 18–35 years, 36–55 and above 55 years. Model…
Donor Genetic Determinant of Thymopoiesis rs2204985 Impacts Clinical Outcome after Single HLA Mismatched HSCT
2021
Abstract Introduction: A common genetic variant within the TCRA-TCRD locus has been recently identified as a predictive factor of thymic function and T cell repertoire diversity (Clave et al., 2018). Specifically it was shown in a mouse model that transplantation of rs2204985 AA human hematopoietic stem cells (HSC) into immunodeficient mice led to lower thymocyte counts and poorer TCR diversity. T cell mediated pathways are known to play a significant role in immunological processes affecting HSCT outcome like GvL, GvH and infection. Aim of this study was to investigate the potential impact of donor rs2204985 genotype on patient's outcome after unrelated HSCT. Methods: The study included 2,…
Matching for the MICA-129 polymorphism is beneficial in unrelated hematopoietic stem cell transplantation.
2016
Major histocompatibility complex class I polypeptide-related sequence A (MICA) is a highly polymorphic ligand of the activating NKG2D receptor on natural killer (NK) cells, γδ-T cells, and NKT cells. MICA incompatibilities have been associated with an increased graft-versus-host disease (GVHD) incidence, and the MICA-129 (met/val) dimorphism has been shown to influence NKG2D signaling in unrelated hematopoietic stem cell transplantation (uHSCT). We investigated the effect of MICA matching on survival after uHSCT. We sequenced 2172 patients and their respective donors for MICA. All patients and donors were high-resolution HLA-typed and matched for 10/10 (n = 1379), 9/10 (n = 636), or 8/10 (n…
Anti-HLA alloantibodies of the IgA isotype in re-transplant candidates part II: Correlation with graft survival
2017
We reported previously on the widespread occurrence of anti-HLA alloantibodies of the IgA isotype (anti-HLA IgA) in the sera of solid-organ re-transplantation (re-tx) candidates (Arnold et al., ). Specifically focussing on kidney re-tx patients, we now extended our earlier findings by examining the impact of the presence and donor specificity of anti-HLA IgA on graft survival. We observed frequent concurrence of anti-HLA IgA and anti-HLA IgG in 27% of our multicenter collective of 694 kidney re-tx patients. This subgroup displayed significantly reduced graft survival as evidenced by the median time to first dialysis after transplantation (TTD 77 months) compared to patients carrying either …
Human leukocyte antigen-E mismatch is associated with better hematopoietic stem cell transplantation outcome in acute leukemia patients
2017
The immunomodulatory role of human leukocyte antigen (HLA)-E in hematopoietic stem cell transplantation (HSCT) has not been extensively investigated. To this end, we genotyped 509 10/10 HLA unrelated transplant pairs for HLA-E, in order to study the effect of HLA-E as a natural killer (NK)-alloreactivity mediator on HSCT outcome in an acute leukemia (AL) setting. Overall survival (OS), disease free survival (DFS), relapse incidence (RI) and non-relapse mortality (NRM) were set as endpoints. Analysis of our data revealed a significant correlation between HLA-E mismatch and improved HSCT outcome, as shown by both univariate (53% vs. 38%, P=0.002, 5-year OS) and multivariate (hazard ratio (HR)…