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Article ; Online: Quality Control for IG /TR Marker Identification and MRD Analysis.

Fronkova, Eva / Svaton, Michael / Trka, Jan

Methods in molecular biology (Clifton, N.J.)

2022 Volume 2453, Page(s) 91–99

Abstract: Selection of the proper target is crucial for clinically relevant monitoring of minimal residual disease (MRD) in patients with acute lymphoblastic leukemia using the quantitation of clonal-specific immunoreceptor (immunoglobulin/T cell receptor) gene ... ...

Abstract	Selection of the proper target is crucial for clinically relevant monitoring of minimal residual disease (MRD) in patients with acute lymphoblastic leukemia using the quantitation of clonal-specific immunoreceptor (immunoglobulin/T cell receptor) gene rearrangements. Consequently, correct interpretation of the results of the entire analysis is of utmost importance. Here we present an overview of the quality control measures that need to be implemented into the process of marker identification, selection, and subsequent quantitation of the MRD level.
MeSH term(s)	Biomarkers ; Humans ; Immunoglobulins/genetics ; Neoplasm, Residual/diagnosis ; Neoplasm, Residual/genetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics ; Quality Control
Chemical Substances	Biomarkers ; Immunoglobulins
Language	English
Publishing date	2022-05-27
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-2115-8_6
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Article ; Online: Functional studies associate novel DUOX2 gene variants detected in heterozygosity to Crohn's disease.

Schwarz, Martin / Gazdarica, Matej / Froňková, Eva / Svatoň, Michael / Bronský, Jiří / Havlovicová, Markéta / Křepelová, Anna / Macek, Milan

Molecular biology reports

2024 Volume 51, Issue 1, Page(s) 399

Abstract: Purpose: Crohn's disease is a chronic gastrointestinal inflammatory disease with possible extraintestinal symptoms. There are predisposing genetic factors and even monogenic variants of the disorder. One of the possible genetic factors are variants of ... ...

Abstract	Purpose: Crohn's disease is a chronic gastrointestinal inflammatory disease with possible extraintestinal symptoms. There are predisposing genetic factors and even monogenic variants of the disorder. One of the possible genetic factors are variants of the DUOX2 gene. The protein product of the DUOX2 gene is a dual oxidase enzyme producing H Methods: Here we present a case report of an adolescent female diagnosed at eleven years of age with IBD that was subsequently reclassified as Crohn's disease. She was treated with immunosuppressants and biological therapy but experienced additional complications. Her peripheral blood lymphocyte DNA was studied using massive parallel sequencing. Detected variants were functionally studied. Results: Whole exome sequencing found two novel DUOX2 gene variants: a de novo variant c.3646C>T; p.R1216W and a maternally inherited variant c.3391G>A; p.A1131T which were initially classified as variants of unknown significance. However, follow-up functional studies demonstrated that both DUOX2 variants led to impaired H Conclusions: Identifying novel variants in patients with Crohn's disease and their families is important for precision medicine approaches and understanding of the pathogenesis of likely "monogenic" rare forms of inflammatory bowel disease.
MeSH term(s)	Humans ; Adolescent ; Female ; Crohn Disease/genetics ; Dual Oxidases/genetics ; Hydrogen Peroxide ; Inflammatory Bowel Diseases/genetics
Chemical Substances	Dual Oxidases (EC 1.11.1.-) ; Hydrogen Peroxide (BBX060AN9V) ; DUOX2 protein, human (EC 1.6.3.1)
Language	English
Publishing date	2024-03-08
Publishing country	Netherlands
Document type	Case Reports ; Journal Article
ZDB-ID	186544-4
ISSN	1573-4978 ; 0301-4851
ISSN (online)	1573-4978
ISSN	0301-4851
DOI	10.1007/s11033-024-09317-8
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Article ; Online: Molecular Screening in Anaplastic Lymphoma Kinase-Positive Anaplastic Large Cell Lymphoma: Anaplastic Lymphoma Kinase Analysis, Next-Generation Sequencing Fusion Gene Detection, and T-Cell Receptor Immunoprofiling.

Kalinova, Marketa / Mrhalova, Marcela / Kabickova, Edita / Svaton, Michael / Skotnicova, Aneta / Prouzova, Zuzana / Krenova, Zdenka / Kolenova, Alexandra / Divoka, Martina / Fronkova, Eva / Kodet, Roman

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc

2024 Volume 37, Issue 3, Page(s) 100428

Abstract: Anaplastic lymphoma kinase-positive anaplastic large cell lymphoma (ALK+ ALCL) originates from the T-lineage and is marked by rearrangements of the ALK gene. More than 10 fusion partners with the ALK gene are known, with the most common being the t(2;5)( ... ...

Abstract	Anaplastic lymphoma kinase-positive anaplastic large cell lymphoma (ALK+ ALCL) originates from the T-lineage and is marked by rearrangements of the ALK gene. More than 10 fusion partners with the ALK gene are known, with the most common being the t(2;5)(p23;q35) translocation resulting in the NPM1::ALK fusion. In 10% to 20% of the ALK+ ALCL cases, the ALK gene fuses with various other partners. Modern molecular techniques, especially next-generation sequencing (NGS), have eased the identification of ALK gene fusion partners and have allowed in-depth characterization of the T-cell receptor (TCR) repertoire. We devised a real-time quantitative reverse-transcription polymerase chain reaction to measure the expression of the translocated portion of the ALK gene. Fusion partners for the ALK gene were analyzed using rapid amplification of 5'cDNA ends (RACE) method or NGS. TCR immunoprofiling was performed by amplicon NGS. We studied 96 ALK+ ALCL patients. NPM1::ALK fusion gene was observed in 71 patients, ATIC::ALK in 9, and TPM3::ALK in 3. CLTC::ALK, MYH9::ALK, and RNF213::ALK fusions were identified in 2 patients each. We also discovered the TPM4::ALK and SATB1::ALK fusion genes, plus the following 2 previously unidentified ALK+ ALCL fusions: SQSTM1::ALK and CAPRIN1::ALK. High expression of the translocated ALK gene segment was observed in all 93 analyzed samples. TCR testing was conducted on 23 patients with available DNA. In 18 (78%) patients, we discerned at least one (ranging from 1 to 4) clonal TCR rearrangement. In 59% of the patients, clonal TCR beta junctions corresponded with sequences previously observed in both healthy donors and under various pathological conditions. Reverse-transcriptase quantitative detection of ALK expression is a fast and reliable method for both diagnosing and monitoring treatment response in ALK+ ALCL patients, irrespective of the ALK gene translocation. NGS reveals new ALK translocation partners. Both malignant and reactive TCR repertoires in ALK+ ALCL patients are unique and do not consistently occur among different patients.
MeSH term(s)	Humans ; Anaplastic Lymphoma Kinase/genetics ; Lymphoma, Large-Cell, Anaplastic/genetics ; Lymphoma, Large-Cell, Anaplastic/pathology ; Receptor Protein-Tyrosine Kinases/genetics ; Protein-Tyrosine Kinases/genetics ; Translocation, Genetic ; Transcription Factors/genetics ; Nuclear Proteins/genetics ; Receptors, Antigen, T-Cell/genetics ; High-Throughput Nucleotide Sequencing ; Matrix Attachment Region Binding Proteins ; Cell Cycle Proteins/genetics ; Adenosine Triphosphatases/genetics ; Ubiquitin-Protein Ligases
Chemical Substances	Anaplastic Lymphoma Kinase (EC 2.7.10.1) ; Receptor Protein-Tyrosine Kinases (EC 2.7.10.1) ; Protein-Tyrosine Kinases (EC 2.7.10.1) ; Transcription Factors ; Nuclear Proteins ; Receptors, Antigen, T-Cell ; SATB1 protein, human ; Matrix Attachment Region Binding Proteins ; CAPRIN1 protein, human ; Cell Cycle Proteins ; RNF213 protein, human (EC 2.3.2.27) ; Adenosine Triphosphatases (EC 3.6.1.-) ; Ubiquitin-Protein Ligases (EC 2.3.2.27)
Language	English
Publishing date	2024-01-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	645073-8
ISSN	1530-0285 ; 0893-3952
ISSN (online)	1530-0285
ISSN	0893-3952
DOI	10.1016/j.modpat.2024.100428
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Article ; Online: Evans syndrome caused by a deleterious mutation affecting the adaptor protein SASH3.

Novak, Wolfgang / Berner, Jakob / Svaton, Michael / Jimenez-Heredia, Raul / Segarra-Roca, Anna / Frohne, Alexandra / Guiliani, Sarah / Rouhani, David / Eder, Sebastian K / Rottal, Arno / Trapin, Doris / Scheuchenstuhl, Anja / Pickl, Winfried F / Simonitsch-Klupp, Ingrid / Kager, Leo / Boztug, Kaan

British journal of haematology

2023 Volume 203, Issue 4, Page(s) 678–683

Abstract: Increasing evidence suggests multilineage cytopenias (also known as Evans syndrome) may be caused by inborn errors of immunity (IEI) with immune dysregulation. We studied a patient with autoimmune haemolytic anaemia and immune thrombocytopenia and ... ...

Abstract	Increasing evidence suggests multilineage cytopenias (also known as Evans syndrome) may be caused by inborn errors of immunity (IEI) with immune dysregulation. We studied a patient with autoimmune haemolytic anaemia and immune thrombocytopenia and identified a germline mutation in SASH3 (c.862C>T;p.Arg288Ter), indicating a recently identified IEI. Immunohistochemistry performed after clinically indicated splenectomy revealed severe hypoplasia/absence of germinal centres. The autoimmune phenotype was associated with an increased CD21
MeSH term(s)	Male ; Humans ; Anemia, Hemolytic, Autoimmune/genetics ; Thrombocytopenia/genetics ; Mutation ; Purpura, Thrombocytopenic, Idiopathic
Language	English
Publishing date	2023-08-30
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80077-6
ISSN	1365-2141 ; 0007-1048
ISSN (online)	1365-2141
ISSN	0007-1048
DOI	10.1111/bjh.19061
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Article ; Online: NGS better discriminates true MRD positivity for the risk stratification of childhood ALL treated on an MRD-based protocol.

Svaton, Michael / Skotnicova, Aneta / Reznickova, Leona / Rennerova, Andrea / Valova, Tatana / Kotrova, Michaela / van der Velden, Vincent H J / Brüggemann, Monika / Darzentas, Nikos / Langerak, Anton W / Zuna, Jan / Stary, Jan / Trka, Jan / Fronkova, Eva

Blood

2022 Volume 141, Issue 5, Page(s) 529–533

Abstract: We compared minimal/measurable residual disease (MRD) levels evaluated by routinely used real-time quantitative polymerase chain reaction (qPCR) patient-specific assays and by next-generation sequencing (NGS) approach in 780 immunoglobulin (IG) and T- ... ...

Abstract	We compared minimal/measurable residual disease (MRD) levels evaluated by routinely used real-time quantitative polymerase chain reaction (qPCR) patient-specific assays and by next-generation sequencing (NGS) approach in 780 immunoglobulin (IG) and T-cell receptor (TR) markers in 432 children with B-cell precursor acute lymphoblastic leukemia treated on the AIEOP-BFM ALL 2009 protocol. Our aim was to compare the MRD-based risk stratification at the end of induction. The results were concordant in 639 of 780 (81.9%) of these markers; 37 of 780 (4.7%) markers were detected only by NGS. In 104 of 780 (13.3%) markers positive only by qPCR, a large fraction (23/104; 22.1%) was detected also by NGS, however, owing to the presence of identical IG/TR rearrangements in unrelated samples, we classified those as nonspecific/false-positive. Risk group stratification based on the MRD results by qPCR and NGS at the end of induction was concordant in 76% of the patients; 19% of the patients would be assigned to a lower risk group by NGS, largely owing to the elimination of false-positive qPCR results, and 5% of patients would be assigned to a higher risk group by NGS. NGS MRD is highly concordant with qPCR while providing more specific results and can be an alternative in the front line of MRD evaluation in forthcoming MRD-based protocols.
MeSH term(s)	Child ; Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy ; Gene Rearrangement ; Receptors, Antigen, T-Cell/genetics ; Immunoglobulins/genetics ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/diagnosis ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/genetics ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/therapy ; Risk Assessment ; High-Throughput Nucleotide Sequencing/methods ; Neoplasm, Residual/diagnosis ; Neoplasm, Residual/genetics
Chemical Substances	Receptors, Antigen, T-Cell ; Immunoglobulins
Language	English
Publishing date	2022-10-03
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood.2022017003
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Article ; Online: Novel XIAP mutation causing enhanced spontaneous apoptosis and disturbed NOD2 signalling in a patient with atypical adult-onset Crohn's disease.

Parackova, Zuzana / Milota, Tomas / Vrabcova, Petra / Smetanova, Jitka / Svaton, Michael / Freiberger, Tomas / Kanderova, Veronika / Sediva, Anna

Cell death & disease

2020 Volume 11, Issue 6, Page(s) 430

Abstract: X-linked inhibitor of apoptosis (XIAP) is the most potent human inhibitor of apoptosis, and is also involved in NOD2-dependent NFκB and MAPK signalling cascade activation. The absence or defective function of XIAP leads to the development of a rare and ... ...

Abstract	X-linked inhibitor of apoptosis (XIAP) is the most potent human inhibitor of apoptosis, and is also involved in NOD2-dependent NFκB and MAPK signalling cascade activation. The absence or defective function of XIAP leads to the development of a rare and severe primary immunodeficiency known as X-linked lymphoproliferative syndrome type 2 (XLP-2), which is characterized by a triad of clinical manifestations, including a high incidence of haemophagocytic lymphohistiocytosis (HLH), lymphoproliferation and inflammatory bowel disease (IBD), usually with very early onset. Here, we present a novel XIAP mutation identified in a patient with atypical adult-onset IBD complicated by relapsing HLH, splenomegaly and sarcoid-like disease. The c.266delA mutation in the XIAP gene creates a premature stop codon, and causes a severe reduction in XIAP protein expression. The mutation is also associated with impaired spontaneous and staurosporine- and PMA-induced apoptosis accompanied by significantly increased expression of pro-apoptotic genes. We also confirmed the negative impact of this particular XIAP mutation on NOD2-dependent NFκB and MAPK activation, while NOD2-independent activation was found to be unaffected. Moreover, we assume that the mutation has an impact on the overproduction of IL-12 and IFNγ, the shift towards the Th1 immune response and increased numbers of central memory and effector memory CD4+ and CD8+ T cells. All these changes contribute to immune dysregulation and the clinical manifestation of XLP-2.
MeSH term(s)	Adult ; Apoptosis ; Crohn Disease/genetics ; Crohn Disease/pathology ; Humans ; Mutation ; Nod2 Signaling Adaptor Protein/metabolism ; Signal Transduction ; X-Linked Inhibitor of Apoptosis Protein/metabolism
Chemical Substances	NOD2 protein, human ; Nod2 Signaling Adaptor Protein ; X-Linked Inhibitor of Apoptosis Protein ; XIAP protein, human
Language	English
Publishing date	2020-06-08
Publishing country	England
Document type	Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2541626-1
ISSN	2041-4889 ; 2041-4889
ISSN (online)	2041-4889
ISSN	2041-4889
DOI	10.1038/s41419-020-2652-4
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Article ; Online: Complex genetic and histopathological study of 15 patient-derived xenografts of aggressive lymphomas.

Jakša, Radek / Karolová, Jana / Svatoň, Michael / Kazantsev, Dmitry / Grajciarová, Martina / Pokorná, Eva / Tonar, Zbyněk / Klánová, Magdalena / Winkowska, Lucie / Maláriková, Diana / Vočková, Petra / Forsterová, Kristina / Renešová, Nicol / Dolníková, Alexandra / Nožičková, Kristýna / Dundr, Pavel / Froňková, Eva / Trněný, Marek / Klener, Pavel

Laboratory investigation; a journal of technical methods and pathology

2022 Volume 102, Issue 9, Page(s) 957–965

Abstract: Non-Hodgkin lymphomas (NHL) represent the most common hematologic malignancies. Patient-derived xenografts (PDXs) are used for various aspects of translational research including preclinical in vivo validation of experimental treatment approaches. While ... ...

Abstract	Non-Hodgkin lymphomas (NHL) represent the most common hematologic malignancies. Patient-derived xenografts (PDXs) are used for various aspects of translational research including preclinical in vivo validation of experimental treatment approaches. While it was repeatedly demonstrated that PDXs keep majority of somatic mutations with the primary lymphoma samples, from which they were derived, the composition of PDX tumor microenvironment (TME) has not been extensively studied. We carried out a comparative genetic and histopathological study of 15 PDX models derived from patients with various types of NHL including diffuse large B-cell lymphoma (DLBCL; n = 7), Burkitt lymphoma (BL; n = 1), mantle cell lymphoma (MCL; n = 2), and peripheral T-cell lymphomas (PTCL; n = 5). Whole exome sequencing (WES) of the PDXs and primary lymphoma cells was implemented in 13 out of 15 cases with available DNA samples. Standard immunohistochemistry (IHC) was used to analyze the composition of PDX TME. WES data confirmed that PDXs maintained the genetic heterogeneity with the original primary lymphoma cells. In contrast, IHC analysis revealed the following recurrently observed alterations in the composition of PDX tumors: more blastoid lymphoma cell morphology, increased proliferation rate, lack of non-malignant cellular components including T cells and (human or murine) macrophages, and significantly lower intratumoral microvessel density and microvessel area composed of murine vessels. In addition, PDX tumors derived from T-NHL displayed additional differences compared to the primary lymphoma samples including markedly lower desmoplasia (i.e., the extent of both reticular and collagen fibrosis), loss of expression of cytotoxic granules (i.e., perforin, TIA, granzyme B), or loss of expression of T-cell specific antigens (i.e., CD3, CD4, CD8). Our data suggest that despite keeping the same genetic profiles, PDX models of aggressive NHL do not recapitulate the microenvironmental heterogeneity of the original lymphomas. These findings have implications on the relevance of PDX models in the context of preclinical research.
MeSH term(s)	Adult ; Animals ; Antineoplastic Agents ; Disease Models, Animal ; Heterografts ; Humans ; Lymphoma, Large B-Cell, Diffuse ; Mice ; Tumor Microenvironment
Chemical Substances	Antineoplastic Agents
Language	English
Publishing date	2022-04-29
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80178-1
ISSN	1530-0307 ; 0023-6837
ISSN (online)	1530-0307
ISSN	0023-6837
DOI	10.1038/s41374-022-00784-w
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Article: Concurrent

Malarikova, Diana / Berkova, Adela / Obr, Ales / Blahovcova, Petra / Svaton, Michael / Forsterova, Kristina / Kriegova, Eva / Prihodova, Eva / Pavlistova, Lenka / Petrackova, Anna / Zemanova, Zuzana / Trneny, Marek / Klener, Pavel

Cancers

2020 Volume 12, Issue 8

Abstract: Mantle cell lymphoma (MCL) is a subtype of B-cell lymphoma with a large number of recurrent cytogenetic/molecular aberrations. Approximately 5-10% of patients do not respond to frontline immunochemotherapy. Despite many useful prognostic indexes, a ... ...

Abstract	Mantle cell lymphoma (MCL) is a subtype of B-cell lymphoma with a large number of recurrent cytogenetic/molecular aberrations. Approximately 5-10% of patients do not respond to frontline immunochemotherapy. Despite many useful prognostic indexes, a reliable marker of chemoresistance is not available. We evaluated the prognostic impact of seven recurrent gene aberrations including tumor suppressor protein P53 (
Language	English
Publishing date	2020-07-31
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers12082120
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Article ; Online: TLR8/TLR7 dysregulation due to a novel TLR8 mutation causes severe autoimmune hemolytic anemia and autoinflammation in identical twins.

Fejtkova, Martina / Sukova, Martina / Hlozkova, Katerina / Skvarova Kramarzova, Karolina / Rackova, Marketa / Jakubec, David / Bakardjieva, Marina / Bloomfield, Marketa / Klocperk, Adam / Parackova, Zuzana / Sediva, Anna / Aluri, Jahnavi / Novakova, Michaela / Kalina, Tomas / Fronkova, Eva / Hrusak, Ondrej / Malcova, Hana / Sedlacek, Petr / Liba, Zuzana /

Kudr, Martin / Stary, Jan / Cooper, Megan A / Svaton, Michael / Kanderova, Veronika

American journal of hematology

2022 Volume 97, Issue 3, Page(s) 338–351

Abstract: Our study presents a novel germline c.1715G>T (p.G572V) mutation in the gene encoding Toll-like receptor 8 (TLR8) causing an autoimmune and autoinflammatory disorder in a family with monozygotic male twins, who suffer from severe autoimmune hemolytic ... ...

Abstract	Our study presents a novel germline c.1715G>T (p.G572V) mutation in the gene encoding Toll-like receptor 8 (TLR8) causing an autoimmune and autoinflammatory disorder in a family with monozygotic male twins, who suffer from severe autoimmune hemolytic anemia worsening with infections, and autoinflammation presenting as fevers, enteritis, arthritis, and CNS vasculitis. The pathogenicity of the mutation was confirmed by in vitro assays on transfected cell lines and primary cells. The p.G572V mutation causes impaired stability of the TLR8 protein, cross-reactivity to TLR7 ligands and reduced ability of TLR8 to attenuate TLR7 signaling. This imbalance toward TLR7-dependent signaling leads to increased pro-inflammatory responses, such as nuclear factor-κB (NF-κB) activation and production of pro-inflammatory cytokines IL-1β, IL-6, and TNFα. This unique TLR8 mutation with partial TLR8 protein loss and hyperinflammatory phenotype mediated by TLR7 ligands represents a novel inborn error of immunity with childhood-onset and a good response to TLR7 inhibition.
MeSH term(s)	Anemia, Hemolytic, Autoimmune/genetics ; Anemia, Hemolytic, Autoimmune/immunology ; Cytokines/genetics ; Cytokines/immunology ; Female ; HEK293 Cells ; Humans ; Inflammation/genetics ; Inflammation/immunology ; Male ; Mutation ; Patient Acuity ; Toll-Like Receptor 7/genetics ; Toll-Like Receptor 7/immunology ; Toll-Like Receptor 8/genetics ; Toll-Like Receptor 8/immunology ; Twins, Monozygotic
Chemical Substances	Cytokines ; TLR7 protein, human ; TLR8 protein, human ; Toll-Like Receptor 7 ; Toll-Like Receptor 8
Language	English
Publishing date	2022-01-28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Twin Study
ZDB-ID	196767-8
ISSN	1096-8652 ; 0361-8609
ISSN (online)	1096-8652
ISSN	0361-8609
DOI	10.1002/ajh.26452
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Article ; Online: Heterologous Cytomegalovirus and Allo-Reactivity by Shared T Cell Receptor Repertoire in Kidney Transplantation.

Stranavova, Lucia / Pelak, Ondrej / Svaton, Michael / Hruba, Petra / Fronkova, Eva / Slavcev, Antonij / Osickova, Klara / Maluskova, Jana / Hubacek, Petr / Fronek, Jiri / Reinke, Petra / Volk, Hans-Dieter / Kalina, Tomas / Viklicky, Ondrej

Frontiers in immunology

2019 Volume 10, Page(s) 2549

Abstract: Cytomegalovirus (CMV) infection is associated with allograft rejection but the mechanisms behind are poorly defined yet. Although cross-reactivity of T cells to alloantigen and CMV has been hypothesized, direct evidence in patients is lacking. In this ... ...

Abstract	Cytomegalovirus (CMV) infection is associated with allograft rejection but the mechanisms behind are poorly defined yet. Although cross-reactivity of T cells to alloantigen and CMV has been hypothesized, direct evidence in patients is lacking. In this observational cohort study, we tested the pre-transplant effector/memory T cell response to CMV peptide pools and alloantigen in 78 living donor/recipient pairs using the interferon-gamma Enzyme-Linked ImmunoSpot (ELISPOT) assay. To prove the hypothesis of cross-reactivity, we analyzed by applying next-generation sequencing the T cell receptor ß (TCR- ß) repertoire of CMV- and alloantigen-reactive T cells enriched from peripheral pre-transplant blood of 11 CMV-seropositive and HLA class I mismatched patients. Moreover, the TCR-repertoire was also analyzed in the allograft biopsies of those patients. There was a significant association between the presence of pre-transplant CMV immediate-early protein 1 (IE-1)-specific effector/memory T cells and acute renal allograft rejection and function (
MeSH term(s)	Adult ; Allografts ; Biopsy ; Cohort Studies ; Cytomegalovirus/immunology ; Cytomegalovirus Infections/etiology ; Cytomegalovirus Infections/genetics ; Cytomegalovirus Infections/immunology ; Cytomegalovirus Infections/pathology ; Female ; Humans ; Immunologic Memory ; Isoantigens/genetics ; Isoantigens/immunology ; Kidney Transplantation ; Male ; Middle Aged ; Receptors, Antigen, T-Cell, alpha-beta/immunology ; T-Lymphocytes/microbiology ; T-Lymphocytes/pathology
Chemical Substances	Isoantigens ; Receptors, Antigen, T-Cell, alpha-beta
Language	English
Publishing date	2019-10-31
Publishing country	Switzerland
Document type	Clinical Trial ; Journal Article ; Observational Study ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2019.02549
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In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito