Peripheral blood stem cell allograft rejection mediated by CD4+ T lymphocytes recognizing a single mismatch at HLA-DPβ1*0901

Fleischhauer, Katharina; Zino, Elisabetta; Mazzi, Benedetta; Sironi, Elisabetta; Servida, Paolo; Zappone, Elisabetta; Benazzi, E.; Bordignon, Claudio

doi:10.1182/blood.v98.4.1122

Cited by 46 publications

(45 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…29 More recently, the alloreactive specificity of such cells for mismatched HLA class I subtypes as well as specific CD4 þ T cells for HLA class II were demonstrated. 30 It is therefore understandable that HLA mismatches between donor and recipient may increase the incidence of rejection, 31 as may preparative regimens with reduced intensity or T cell depletion of the grafts. 32 To overcome the HLA barrier, most conditioning regimens for haplotransplantation in children were myeloablative and BU or TBI (14.4 or 12 Gy) based.…”

Section: Engraftment and Gvhdmentioning

confidence: 99%

Haploidentical SCT in children: an update and future perspectives

Lang

Handgretinger

2008

Bone Marrow Transplant

View full text Add to dashboard Cite

Transplantation of haploidentical stem cells has become a well-established approach, which makes a potential donor available for almost all patients. This review focuses on current results and new strategies, especially in pediatric patients with malignant diseases. CD34 þ positive selection was the most common procedure for graft manipulation in the past years, whereas T and B cell depletion is a promising new method. GVHD could herewith be effectively reduced and primary engraftment was reported in 83-100% of patients after transplantation of high stem cell doses. For patients with ALL in remission, diseasefree survival at 3 years ranged between 22 and 48%. TRM, mainly because of viral infections, was improved by the use of reduced-intensity conditioning (which helped to speed up T cell recovery) and by close monitoring of viral loads and prophylactic/preemptive therapy. The role of donor-derived Ag-specific T cells against viral and fungal antigens is currently under investigation. Patients with active disease at the time of transplantation had a poor outcome and several attempts to improve these results are currently evaluated, such as co-infusion of natural killer cells, co-transplantation of MSC, use of new antileukemic drugs and post-transplant immunotherapy.

show abstract

Section: Engraftment and Gvhdmentioning

confidence: 99%

Haploidentical SCT in children: an update and future perspectives

Lang

Handgretinger

2008

Bone Marrow Transplant

View full text Add to dashboard Cite

show abstract

“…In fact, previous studies demonstrated that host T cells that recognize donor HLA Ags emerge at the time of graft failure. 3,4 Nevertheless, recent animal studies have demonstrated that preformed Ab, not primed T cells, is the initial and major barrier to BM engraftment in allosensitized recipients. 5 Moreover, Ab-mediated rejection is a well-recognized cause of treatment failure in the field of solid organ transplantation.…”

Section: Introductionmentioning

confidence: 99%

Risk and prevention of graft failure in patients with preexisting donor-specific HLA antibodies undergoing unmanipulated haploidentical SCT

Yoshihara

Maruya²,

Taniguchi

et al. 2011

Bone Marrow Transplant

195

201

View full text Add to dashboard Cite

A role of donor-specific HLA antibodies (DSA) in graft failure after SCT has been suggested, but the relevance of DSA in unmanipulated haploidentical SCT (haplo-SCT) remains unknown. We prospectively examined HLA antibodies using the Luminex-based single Ag assay for 79 adult patients undergoing unmanipulated haplo-SCT. Among them, 16 (20.2%) were HLA Ab-positive, including five patients with antibodies not corresponding to donor HLA Ags and 11 DSA-positive patients. Of the 11 DSA-positive patients, five received treatments to decrease DSA levels, including two, who received plasma exchange and rituximab, two who received platelet transfusions from healthy-related donors having DSAcorresponding HLA Ags and one who received bortezomib. Platelet transfusion was the most simple and effective treatment option for class I DSA. The cumulative incidence of neutrophil recovery was significantly lower in pretransplant (post-treatment) DSA-positive patients than in DSA-negative patients (61.9 vs 94.4%, P ¼ 0.026). Notably, three of five patients with high levels of DSA had graft failure. Donors should be selected on the basis of an evaluation of HLA antibodies. If haplo-SCT from donors with HLA Ags that correspond to high levels of DSA must be performed, then recipients should be treated for DSA to improve the chances of successful donor engraftment.

show abstract

“…45 Initial evidence for a role of HLA-DPB1 in UD-HCT has been reported since the mid-1990s, 34,35,[46][47][48] and a large body of literature has accumulated to date (Table 1). Experimentally, the ability of a wide range of HLA-DPB1 allele mismatches to elicit polyclonal alloreactive T-cell responses has been confirmed.…”

mentioning

confidence: 99%

HLA-DP in unrelated hematopoietic cell transplantation revisited: challenges and opportunities

Fleischhauer

Shaw

2017

Blood

Self Cite

View full text Add to dashboard Cite

When considering HLA-matched hematopoietic cell transplantation (HCT), sibling and unrelated donors (UDs) are biologically different because UD-HCT is typically performed across HLA-DP disparities absent in sibling HCT. Mismatched HLA-DP is targeted by direct alloreactive T cell responses with important implications for graft-versus-host disease and graft-versus-leukemia. This concise review details special features of HLA-DP as model antigens for clinically permissive mismatches mediating limited T-cell alloreactivity with minimal toxicity, and describes future avenues for their exploitation in cellular immunotherapy of malignant blood disorders.

show abstract

Peripheral blood stem cell allograft rejection mediated by CD4+ T lymphocytes recognizing a single mismatch at HLA-DPβ1*0901

Cited by 46 publications

References 25 publications

Haploidentical SCT in children: an update and future perspectives

Haploidentical SCT in children: an update and future perspectives

Risk and prevention of graft failure in patients with preexisting donor-specific HLA antibodies undergoing unmanipulated haploidentical SCT

HLA-DP in unrelated hematopoietic cell transplantation revisited: challenges and opportunities

Contact Info

Product

Resources

About