Donor Genotype in the Interleukin-7 Receptor α-Chain Predicts Risk of Graft-versus-Host Disease and Cytomegalovirus Infection after Allogeneic Hematopoietic Stem Cell Transplantation.

Abstract:

:The efficacy of allogeneic hematopoietic stem cell transplantation (HSCT) is challenged by acute and chronic graft-versus-host disease (aGVHD and cGVHD) and viral infections due to long-lasting immunodeficiency. Interleukin-7 (IL-7) is a cytokine essential for de novo T cell generation in thymus and peripheral T cell homeostasis. In this study, we investigated the impact of the single nucleotide polymorphism rs6897932 in the IL-7 receptor α-chain (IL-7Rα) which has previously been associated with several autoimmune diseases. We included 460 patients undergoing allogeneic HSCT after a myeloablative conditioning. Patients had a median age of 26.3 years (0.3-67.0 years), and 372 (80.9%) underwent HSCT for malignant diseases. Donors were matched sibling donors (n = 147), matched unrelated donors (n = 244) or mismatched unrelated donors (n = 69), and the stem cell source were either bone marrow (n = 329) or peripheral blood (n = 131). DNA from donors was genotyped for the IL-7Rα single nucleotide polymorphism (SNP) rs6897932 using an allele-specific primer extension assay (CC: n = 252, CT: n = 178, TT: n = 30). The donor T allele was associated with a higher risk of grades III-IV aGVHD (HR = 2.0, 95% CI = 1.1-3.8, P = 0.034) and with significantly increased risk of extensive cGVHD (HR = 2.0, 95% CI = 1.1-3.6, P = 0.025) after adjustment for potential risk factors. In addition, the TT genotype was associated with a higher risk of cytomegalovirus (CMV) infection post-transplant (HR = 2.4, 95% CI = 1.2-4.3, P = 0.0068). Numbers of T cells were significantly higher on day +60 in patients receiving a rs6897932 TT graft (CD3+: 109% increase, P = 0.0096; CD4+: 64% increase, P = 0.038; CD8+: 133% increase, P = 0.011). Donor heterozygosity for the T allele was associated with inferior overall survival (HR = 1.7, 95% CI = 1.2-2.3, P = 0.0027) and increased treatment-related mortality (HR = 2.3, 95% CI = 1.3-4.0, P = 0.0047), but was not associated with the risk of relapse (P = 0.35). In conclusion, the IL-7Rα rs6897932 genotype of the donor is predictive of aGVHD and cGVHD, CMV infection, and mortality following HSCT. These findings indicate that IL-7Rα SNP typing of donors may optimize donor selection and facilitate individualization of treatment in order to limit treatment-related complications.

journal_name

Front Immunol

journal_title

Frontiers in immunology

authors

Kielsen K,Enevold C,Heilmann C,Sengeløv H,Pedersen AE,Ryder LP,Müller K

doi

10.3389/fimmu.2018.00109

subject

Has Abstract

pub_date

2018-02-02 00:00:00

pages

109

issn

1664-3224

journal_volume

9

pub_type

杂志文章
  • Molecular and Cellular Interactions of Scavenger Receptor SR-F1 With Complement C1q Provide Insights Into Its Role in the Clearance of Apoptotic Cells.

    abstract::The scavenger receptor SR-F1 binds to and mediates the internalization of a wide range of ligands, and is involved in several immunological processes. We produced recombinant SR-F1 ectodomain and fragments deleted from the last 2 or 5 C-terminal epidermal growth factor-like modules and investigated their role in the b...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.00544

    authors: Wicker-Planquart C,Dufour S,Tacnet-Delorme P,Bally I,Delneste Y,Frachet P,Housset D,Thielens NM

    更新日期:2020-03-31 00:00:00

  • Public Clonotypes and Convergent Recombination Characterize the Naïve CD8+ T-Cell Receptor Repertoire of Extremely Preterm Neonates.

    abstract::Respiratory support improvements have aided survival of premature neonates, but infection susceptibility remains a predominant problem. We previously reported that neonatal mice have a rapidly evolving T-cell receptor (TCR) repertoire that impairs CD8+ T cell immunity. To understand the impact of prematurity on the hu...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2017.01859

    authors: Carey AJ,Hope JL,Mueller YM,Fike AJ,Kumova OK,van Zessen DBH,Steegers EAP,van der Burg M,Katsikis PD

    更新日期:2017-12-19 00:00:00

  • Therapeutic Inhibition of the Complement System in Diseases of the Central Nervous System.

    abstract::The complement system plays critical roles in development, homeostasis, and regeneration in the central nervous system (CNS) throughout life; however, complement dysregulation in the CNS can lead to damage and disease. Complement proteins, regulators, and receptors are widely expressed throughout the CNS and, in many ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2019.00362

    authors: Carpanini SM,Torvell M,Morgan BP

    更新日期:2019-03-04 00:00:00

  • Manufacturing and Management of CAR T-Cell Therapy in "COVID-19's Time": Central Versus Point of Care Proposals.

    abstract::The COVID-19 pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), has generated a significant repercussion on the administration of adoptive cell therapies, including chimeric antigen receptor (CAR) T-cells. The closing of borders, the reduction of people transit and the confinement of the...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2020.573179

    authors: Ortiz de Landazuri I,Egri N,Muñoz-Sánchez G,Ortiz-Maldonado V,Bolaño V,Guijarro C,Pascal M,Juan M

    更新日期:2020-10-15 00:00:00

  • GMP-Grade Manufacturing of T Cells Engineered to Express a Defined γδTCR.

    abstract::γ9δ2T cells play a critical role in daily cancer immune surveillance by sensing cancer-mediated metabolic changes. However, a major limitation of the therapeutic application of γ9δ2T cells is their diversity and regulation through innate co-receptors. In order to overcome natural obstacles of γ9δ2T cells, we have deve...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.01062

    authors: Straetemans T,Kierkels GJJ,Doorn R,Jansen K,Heijhuurs S,Dos Santos JM,van Muyden ADD,Vie H,Clemenceau B,Raymakers R,de Witte M,Sebestyén Z,Kuball J

    更新日期:2018-05-30 00:00:00

  • O-Serotype Conversion in Salmonella Typhimurium Induces Protective Immune Responses against Invasive Non-Typhoidal Salmonella Infections.

    abstract::Salmonella infections remain a big problem worldwide, causing enteric fever by Salmonella Typhi (or Paratyphi) or self-limiting gastroenteritis by non-typhoidal Salmonella (NTS) in healthy individuals. NTS may become invasive and cause septicemia in elderly or immuno-compromised individuals, leading to high mortality ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2017.01647

    authors: Li P,Liu Q,Luo H,Liang K,Yi J,Luo Y,Hu Y,Han Y,Kong Q

    更新日期:2017-12-04 00:00:00

  • Genome-Wide Association Study on Immunoglobulin G Glycosylation Patterns.

    abstract::Immunoglobulin G (IgG), a glycoprotein secreted by plasma B-cells, plays a major role in the human adaptive immune response and are associated with a wide range of diseases. Glycosylation of the Fc binding region of IgGs, responsible for the antibody's effector function, is essential for prompting a proper immune resp...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.00277

    authors: Wahl A,van den Akker E,Klaric L,Štambuk J,Benedetti E,Plomp R,Razdorov G,Trbojević-Akmačić I,Deelen J,van Heemst D,Slagboom PE,Vučković F,Grallert H,Krumsiek J,Strauch K,Peters A,Meitinger T,Hayward C,Wuhrer M,Beekm

    更新日期:2018-02-26 00:00:00

  • Longer Duration of SARS-CoV-2 Infection in a Case of Mild COVID-19 With Weak Production of the Specific IgM and IgG Antibodies.

    abstract::Background: The relationship between SARS-CoV-2-carrying time and specific antibody production has not yet been reported in re-admitted COVID-19 patients. We reported a case of mild COVID-19 with long virus-carrying time, weak production of virus-specific IgG and IgM antibodies, and recurrence of positive SARS-CoV-2 R...

    journal_title:Frontiers in immunology

    pub_type:

    doi:10.3389/fimmu.2020.01936

    authors: Guo X,Zeng L,Huang Z,He Y,Zhang Z,Zhong Z

    更新日期:2020-08-07 00:00:00

  • Podocytes and Proteinuria in ANCA-Associated Glomerulonephritis: A Case-Control Study.

    abstract::Proteinuria has been identified as prognosticator of renal outcome in patients with ANCA-associated glomerulonephritis, but whether proteinuria is related to podocyte abnormalities in these patients is largely unknown. We here investigate podocyte foot process width and number of podocytes positive for the podocyte ma...

    journal_title:Frontiers in immunology

    pub_type: 临床试验,杂志文章

    doi:10.3389/fimmu.2019.01405

    authors: van Daalen EE,Neeskens P,Zandbergen M,Harper L,Karras A,Vaglio A,de Zoysa J,Bruijn JA,Bajema IM

    更新日期:2019-06-26 00:00:00

  • Epigenetic and Transcriptional Regulation in the Induction, Maintenance, Heterogeneity, and Recall-Response of Effector and Memory Th2 Cells.

    abstract::Antigen-primed T cells respond to restimulation much faster than naïve T cells and form the cellular basis of immunological memory. The formation of memory Th2 cells starts when naïve CD4 T cells are transformed into effector Th2 cells and is completed after antigen clearance and a long-term resting phase accompanied ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2018.02929

    authors: Onodera A,Kokubo K,Nakayama T

    更新日期:2018-12-12 00:00:00

  • Identification of CVID Patients With Defects in Immune Repertoire Formation or Specification.

    abstract::Common variable immune deficiency disorder (CVID) is the most clinically relevant cause of antibody failure. It is a highly heterogeneous disease with different underlying etiologies. CVID has been associated with a quantitative B cell defect, however, little is known about the quality of B cells present. Here, we stu...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.02545

    authors: van Schouwenburg PA,IJspeert H,Pico-Knijnenburg I,Dalm VASH,van Hagen PM,van Zessen D,Stubbs AP,Patel SY,van der Burg M

    更新日期:2018-11-23 00:00:00

  • The Length of N-Glycans of Recombinant H5N1 Hemagglutinin Influences the Oligomerization and Immunogenicity of Vaccine Antigen.

    abstract::Hemagglutinin glycoprotein (HA) is a principle influenza vaccine antigen. Recombinant HA-based vaccines become a potential alternative for traditional approach. Complexity and variation of HA N-glycosylation are considered as the important factors for the vaccine design. The number and location of glycan moieties in t...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2017.00444

    authors: Macioła AK,Pietrzak MA,Kosson P,Czarnocki-Cieciura M,Śmietanka K,Minta Z,Kopera E

    更新日期:2017-04-20 00:00:00

  • Chymase-Cre; Mcl-1fl/fl Mice Exhibit Reduced Numbers of Mucosal Mast Cells.

    abstract::Mast cells (MCs) are considered as key effector cells in the elicitation of allergic symptoms, and they are essential players in innate and adaptive immune responses. In mice, two main types of MCs have been described: connective tissue MCs (CTMCs) and mucosal MCs (MMCs). However, little is known about the biological ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.02399

    authors: Luo Y,Meyer N,Jiao Q,Scheffel J,Zimmermann C,Metz M,Zenclussen A,Maurer M,Siebenhaar F

    更新日期:2019-10-15 00:00:00

  • Emerging Mechanisms of Insulin-Mediated Antiviral Immunity in Drosophila melanogaster.

    abstract::Arboviruses (arthropod-borne viruses), such as Zika (ZIKV), West Nile (WNV), and dengue (DENV) virus, include some of the most significant global health risks to human populations. The steady increase in the number of cases is of great concern due to the debilitating diseases associated with each viral infection. Beca...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2019.02973

    authors: Trammell CE,Goodman AG

    更新日期:2019-12-20 00:00:00

  • Cell Differentiation Degree as a Factor Determining the Role for Different T-Helper Populations in Tuberculosis Protection.

    abstract::Efficient tuberculosis (TB) control depends on early TB prediction and prevention. Solution to these tasks requires knowledge of TB protection correlates (TB CoPs), i.e., laboratory markers that are mechanistically involved in the protection and which allow to determine how well an individual is protected against TB o...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2019.00972

    authors: Lyadova I,Nikitina I

    更新日期:2019-05-08 00:00:00

  • The Concerted Action of E2-2 and HEB Is Critical for Early Lymphoid Specification.

    abstract::The apparition of adaptive immunity in Gnathostomata correlates with the expansion of the E-protein family to encompass E2-2, HEB, and E2A. Within the family, E2-2 and HEB are more closely evolutionarily related but their concerted action in hematopoiesis remains to be explored. Here we show that the combined disrupti...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.00455

    authors: Bouderlique T,Peña-Pérez L,Kharazi S,Hils M,Li X,Krstic A,De Paepe A,Schachtrup C,Gustafsson C,Holmberg D,Schachtrup K,Månsson R

    更新日期:2019-03-18 00:00:00

  • CD24 Expression and B Cell Maturation Shows a Novel Link With Energy Metabolism: Potential Implications for Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

    abstract::CD24 expression on pro-B cells plays a role in B cell selection and development in the bone marrow. We previously detected higher CD24 expression and frequency within IgD+ naïve and memory B cells in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) compared with age-matched healthy controls (H...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.02421

    authors: Mensah FFK,Armstrong CW,Reddy V,Bansal AS,Berkovitz S,Leandro MJ,Cambridge G

    更新日期:2018-10-22 00:00:00

  • Killer Ig-Like Receptors (KIRs): Their Role in NK Cell Modulation and Developments Leading to Their Clinical Exploitation.

    abstract::Natural killer (NK) cells contribute to the first line of defense against viruses and to the control of tumor growth and metastasis spread. The discovery of HLA class I specific inhibitory receptors, primarily of killer Ig-like receptors (KIRs), and of activating receptors has been fundamental to unravel NK cell funct...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2019.01179

    authors: Pende D,Falco M,Vitale M,Cantoni C,Vitale C,Munari E,Bertaina A,Moretta F,Del Zotto G,Pietra G,Mingari MC,Locatelli F,Moretta L

    更新日期:2019-05-28 00:00:00

  • Advances in the Isolation of Specific Monoclonal Rabbit Antibodies.

    abstract::The rabbit monoclonal antibodies (mAbs) have advantages in pharmaceuticals and diagnostics with high affinity and specificity. During the past decade, many techniques have been developed for isolating rabbit mAbs, including single B cell antibody technologies. This review describes the basic characterization of rabbit...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2017.00494

    authors: Zhang Z,Liu H,Guan Q,Wang L,Yuan H

    更新日期:2017-05-05 00:00:00

  • MMP-9/Gelatinase B Degrades Immune Complexes in Systemic Lupus Erythematosus.

    abstract::Systemic Lupus Erythematosus (SLE) is a common and devastating autoimmune disease, characterized by a dysregulated adaptive immune response against intracellular antigens, which involves both autoreactive T and B cells. In SLE, mainly intracellular autoantigens generate autoantibodies and these assemble into immune co...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.00538

    authors: Ugarte-Berzal E,Boon L,Martens E,Rybakin V,Blockmans D,Vandooren J,Proost P,Opdenakker G

    更新日期:2019-03-22 00:00:00

  • Effect of Roux-en-Y Bariatric Surgery on Lipoproteins, Insulin Resistance, and Systemic and Vascular Inflammation in Obesity and Diabetes.

    abstract:Purpose:Obesity is a major modifiable risk factor for cardiovascular disease. Bariatric surgery is considered to be the most effective treatment option for weight reduction in obese patients with and without type 2 diabetes (T2DM). Objective:To evaluate changes in lipoproteins, insulin resistance, mediators of systemi...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2017.01512

    authors: Yadav R,Hama S,Liu Y,Siahmansur T,Schofield J,Syed AA,France M,Pemberton P,Adam S,Ho JH,Aghamohammadzadeh R,Dhage S,Donn R,Malik RA,New JP,Jeziorska M,Durrington P,Ammori BA,Soran H

    更新日期:2017-11-15 00:00:00

  • Time Course of Immune Response and Immunomodulation During Normal and Delayed Healing of Musculoskeletal Wounds.

    abstract::Single trauma injuries or isolated fractures are often manageable and generally heal without complications. In contrast, high-energy trauma results in multi/poly-trauma injury patterns presenting imbalanced pro- and anti- inflammatory responses often leading to immune dysfunction. These injuries often exhibit delayed ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2020.01056

    authors: Muire PJ,Mangum LH,Wenke JC

    更新日期:2020-06-04 00:00:00

  • The WNT Framework in Shaping Immune Cell Responses During Bacterial Infections.

    abstract::A large proportion of the world is inflicted with health concerns arising from infectious diseases. Moreover, there is a widespread emergence of antibiotic resistance among major infectious agents, partially stemming from their continuous dialog with the host, and their enormous capacity to remodel the latter toward a...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2019.01985

    authors: Mukherjee T,Balaji KN

    更新日期:2019-08-21 00:00:00

  • A Unique Cellular and Molecular Microenvironment Is Present in Tertiary Lymphoid Organs of Patients with Spontaneous Prostate Cancer Regression.

    abstract:OBJECTIVE:Multiple solid cancers contain tertiary lymphoid organs (TLO). However, it is unclear whether they promote tumor rejection, facilitate tumor evasion, or simply whether they are a byproduct of chronic inflammation. We hypothesize that although chronic inflammation induces TLO formation, the tumor milieu can mo...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2017.00563

    authors: García-Hernández ML,Uribe-Uribe NO,Espinosa-González R,Kast WM,Khader SA,Rangel-Moreno J

    更新日期:2017-05-17 00:00:00

  • Forward Vaccinology: CTL Targeting Based upon Physical Detection of HLA-Bound Peptides.

    abstract::Vaccine-elicited cytotoxic T lymphocytes (CTL) recognizing conserved fragments of a pathogen's proteome could greatly impact infectious diseases and cancers. Enabling this potential are recent advances in mass spectrometry that identify specific target peptides among the myriad HLA-bound peptides on altered cells. Ult...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2014.00418

    authors: Reinherz EL,Keskin DB,Reinhold B

    更新日期:2014-09-04 00:00:00

  • The Cholinergic System Modulates Memory and Hippocampal Plasticity via Its Interactions with Non-Neuronal Cells.

    abstract::Degeneration of central cholinergic neurons impairs memory, and enhancement of cholinergic synapses improves cognitive processes. Cholinergic signaling is also anti-inflammatory, and neuroinflammation is increasingly linked to adverse memory, especially in Alzheimer's disease. Much of the evidence surrounding choliner...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2017.01489

    authors: Maurer SV,Williams CL

    更新日期:2017-11-08 00:00:00

  • IFN signaling: how a non-canonical model led to the development of IFN mimetics.

    abstract::The classical model of cytokine signaling dominates our view of specific gene activation by cytokines such as the interferons (IFNs). The importance of the model extends beyond cytokines and applies to hormones such as growth hormone (GH) and insulin, and growth factors such as epidermal growth factor (EGF) and fibrob...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2013.00202

    authors: Johnson HM,Noon-Song EN,Dabelic R,Ahmed CM

    更新日期:2013-07-25 00:00:00

  • Adenovirus VA RNAI Blocks ASC Oligomerization and Inhibits NLRP3 Inflammasome Activation.

    abstract::Virus infected immune cells can rapidly respond to the invader by activating the inflammasome and as a consequence release proinflammatory cytokines and eventually die by pyroptosis. In human adenovirus-5 (Ad5) infected THP-1 cells, inhibition of NLRP3 inflammasome activation was demonstrated by a decreased secretion ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.02791

    authors: Darweesh M,Kamel W,Gavrilin MA,Akusjärvi G,Svensson C

    更新日期:2019-11-28 00:00:00

  • Coupling of HIV-1 Antigen to the Selective Autophagy Receptor SQSTM1/p62 Promotes T-Cell-Mediated Immunity.

    abstract::Vaccines aiming to promote T-cell-mediated immune responses have so far showed limited efficacy, and there is a need for novel strategies. Studies indicate that autophagy plays an inherent role in antigen processing and presentation for CD4(+) and CD8(+) T cells. Here, we report a novel vaccine strategy based on fusio...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2016.00167

    authors: Andersen AN,Landsverk OJ,Simonsen A,Bogen B,Corthay A,Øynebråten I

    更新日期:2016-05-10 00:00:00

  • Neoantigen Vaccine Delivery for Personalized Anticancer Immunotherapy.

    abstract::Cancer neoantigens derived from random somatic mutations in tumor tissue represent an attractive type of targets for the cancer immunotherapies including cancer vaccine. Vaccination against the tumor-specific neoantigens minimizes the potential induction of central and peripheral tolerance as well as the risk of autoi...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2018.01499

    authors: Guo Y,Lei K,Tang L

    更新日期:2018-07-02 00:00:00