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Article ; Online: HLA-C07:1044N a novel allele, caused by a single nucleotide deletion in exon 3 of HLA-C07:01:01:01.

Verboom, Murielle / Vergin, Lina / Streich, Hannah / Hallensleben, Michael

2023 Volume 101, Issue 6, Page(s) 687–688

Abstract: HLA-C*07:1044N differs from HLA-C*07:01:01:01 by a single nucleotide deletion in exon 3, codon 124, nt. 442. ...

Abstract	HLA-C07:1044N differs from HLA-C07:01:01:01 by a single nucleotide deletion in exon 3, codon 124, nt. 442.
MeSH term(s)	Humans ; HLA-C Antigens/genetics ; Nucleotides ; Alleles ; Exons/genetics ; Codon ; Sequence Analysis, DNA ; Histocompatibility Testing
Chemical Substances	HLA-C Antigens ; Nucleotides ; Codon
Language	English
Publishing date	2023-01-20
Publishing country	England
Document type	Journal Article
ZDB-ID	2845111-9
ISSN	2059-2310 ; 2059-2302
ISSN (online)	2059-2310
ISSN	2059-2302
DOI	10.1111/tan.14970
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Zs.A 661: Show issues

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Article ; Online: The novel HLA-DQB106 null allele, HLA-DQB106:423N, identified in a volunteer blood donor.

Loeser, Evelyn / Hallensleben, Michael / Bernheiden, Martin / Rakhmanov, Mirzokhid / Emmerich, Florian

HLA

2022 Volume 100, Issue 2, Page(s) 186–188

Abstract: A single nucleotide exchange in exon 2 at position 370 (C ->T) generates a preterminal STOP encoding a C-terminally truncated protein. ...

Abstract	A single nucleotide exchange in exon 2 at position 370 (C ->T) generates a preterminal STOP encoding a C-terminally truncated protein.
MeSH term(s)	Alleles ; Blood Donors ; HLA-DQ beta-Chains/genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Volunteers
Chemical Substances	HLA-DQ beta-Chains ; HLA-DQB1 antigen
Language	English
Publishing date	2022-05-18
Publishing country	England
Document type	Journal Article
ZDB-ID	2845111-9
ISSN	2059-2310 ; 2059-2302
ISSN (online)	2059-2310
ISSN	2059-2302
DOI	10.1111/tan.14641
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Zs.A 661: Show issues

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Book ; Thesis: Experimentelle Untersuchungen zur Genetik des Diabetes mellitus Typ 2

Hallensleben, Michael

1998

Author's details	vorgelegt von Michael Hallensleben
Language	German
Size	VII, 95 Bl. : Ill., graph. Darst.
Document type	Book ; Thesis
Thesis / German Habilitation thesis	Hannover, Med. Hochsch., Diss., 1999
HBZ-ID	HT011140726
Database	Catalogue ZB MED Medicine, Health

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Article ; Online: An Improved Protocol for Targeted Differentiation of Primed Human Induced Pluripotent Stem Cells into HLA-G-Expressing Trophoblasts to Enable the Modeling of Placenta-Related Disorders.

Shum, Ian O / Merkert, Sylvia / Malysheva, Svitlana / Jahn, Kirsten / Lachmann, Nico / Verboom, Murielle / Frieling, Helge / Hallensleben, Michael / Martin, Ulrich

Cells

2023 Volume 12, Issue 16

Abstract: Abnormalities at any stage of trophoblast development may result in pregnancy-related complications. Many of these adverse outcomes are discovered later in pregnancy, but the underlying pathomechanisms are constituted during the first trimester. ... ...

Abstract	Abnormalities at any stage of trophoblast development may result in pregnancy-related complications. Many of these adverse outcomes are discovered later in pregnancy, but the underlying pathomechanisms are constituted during the first trimester. Acquiring developmentally relevant material to elucidate the disease mechanisms is difficult. Human pluripotent stem cell (hPSC) technology can provide a renewable source of relevant cells. BMP4, A83-01, and PD173074 (BAP) treatment drives trophoblast commitment of hPSCs toward syncytiotrophoblast (STB), but lacks extravillous trophoblast (EVT) cells. EVTs mediate key functions during placentation, remodeling of uterine spiral arteries, and maintenance of immunological tolerance. We optimized the protocol for a more efficient generation of HLA-G
MeSH term(s)	Female ; Pregnancy ; Humans ; HLA-G Antigens ; Trophoblasts ; Induced Pluripotent Stem Cells ; Cell Differentiation
Chemical Substances	HLA-G Antigens ; A-83-01
Language	English
Publishing date	2023-08-15
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells12162070
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Article ; Online: In-Depth Profiling of T-Cell Responsiveness to Commonly Recognized CMV Antigens in Older People Reveals Important Sex Differences.

Reus, Bernhard / Caserta, Stefano / Larsen, Martin / Morrow, George / Bano, Aalia / Hallensleben, Michael / Rajkumar, Chakravarthi / Pera, Alejandra / Kern, Florian

Frontiers in immunology

2021 Volume 12, Page(s) 707830

Abstract: The impact of biological sex on T-cell immunity to Cytomegalovirus (CMV) has not been investigated in detail with only one published study comparing CMV-specific T-cell responses in men and women. Many studies, however, have shown an association between ... ...

Abstract	The impact of biological sex on T-cell immunity to Cytomegalovirus (CMV) has not been investigated in detail with only one published study comparing CMV-specific T-cell responses in men and women. Many studies, however, have shown an association between CMV infection and immunosenescence, with broad effects on peripheral blood lymphocyte subsets as well as the T and B-cell repertoires. Here, we provide a detailed analysis of CMV-specific T-cell responses in (n=94) CMV+ older people, including 47 women and 47 men aged between 60 and 93 years. We explore sex differences with respect to 16 different CMV proteins arranged in 14 peptide pools (overlapping peptides). Following ex vivo stimulation, CD4 and CD8 T-cells producing IFN-γ, TNF, and IL-2 were enumerated by flow-cytometry (intracellular cytokine staining). T-cell responses were evaluated in terms of each cytokine separately or in terms of cytokines produced simultaneously (polyfunctionality). Surface memory phenotype and CD3 downmodulation were assessed in parallel. The polyfunctionality index and a memory subset differentiation score were used to identify associations between response size, cytokine production, polyfunctionality, and memory subset distribution. While no significant sex differences were found with respect to overall CMV target protein selection, the T-cell response in men appeared more focused and accompanied by a more prominent accumulation of CMV-specific memory CD4 and CD8 T-cells. T-cell polyfunctionality and differentiation were similar in the sexes, however, CMV-specific T-cells in men produced more pro-inflammatory cytokines. Particularly, TNF production by CD4 T-cells was stronger in men than in women. Also, compared with women, men had larger responses to CMV proteins with immediate-early/early kinetics than women, which might have been driven by CMV reactivation. In conclusion, the CMV-specific T-cell response in men was larger and more pro-inflammatory than in women. Our findings may help explain sex differences in CMV-associated pathologies.
MeSH term(s)	Aged ; Aged, 80 and over ; Antigens, Viral/immunology ; CD4-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/immunology ; Cytomegalovirus/immunology ; Cytomegalovirus Infections/immunology ; Female ; Humans ; Immunosenescence/immunology ; Male ; Middle Aged ; Sex Characteristics
Chemical Substances	Antigens, Viral
Language	English
Publishing date	2021-08-13
Publishing country	Switzerland
Document type	Journal Article ; 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.2021.707830
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Article ; Online: Assignment of C1q-binding HLA antibodies as unacceptable HLA antigens avoids positive CDC-crossmatches prior to transplantation of deceased donor organs.

Juhl, David / Marget, Matthias / Hallensleben, Michael / Görg, Siegfried / Ziemann, Malte

Transplant immunology

2017 Volume 41, Page(s) 17–21

Abstract: Soon, a virtual crossmatch shall replace the complement-dependent cytotoxicity (CDC) allocation crossmatch in the Eurotransplant region. To prevent positive CDC-crossmatches in the recipient centre, careful definition of unacceptable antigens is ... ...

Abstract	Soon, a virtual crossmatch shall replace the complement-dependent cytotoxicity (CDC) allocation crossmatch in the Eurotransplant region. To prevent positive CDC-crossmatches in the recipient centre, careful definition of unacceptable antigens is necessary. For highly sensitized patients, this is difficult by CDC alone. Assignment of all antibodies detected by sensitive assays, however, could prevent organ allocation. To assess the usefulness of the Luminex C1q-assay to prevent positive CDC-crossmatches, all CDC-crossmatches performed prior to deceased kidney transplantation in a 16-month-period were reviewed. Sera causing positive crossmatches were investigated by the C1q-assay. 31 out of 1432 crossmatches (2.2%) were positive. Sera involved in 26 positive crossmatches were available. C1q-binding donor-specific antibodies were detected in 19 sera (73.1%). The other sera were from recipients without any HLA antibodies detectable by CDC or common solid phase assays. Three patients had known Non-HLA antibodies causing positive CDC-results. Four crossmatches were only weak positive. Therefore, avoidance of donors with HLA antigens against whom C1q-binding antibodies were detected would have prevented all positive crossmatches due to HLA antibodies. Provided that all HLA specificities against which antibodies are detected by the Luminex C1q-assay are considered as unacceptable antigens, CDC-crossmatches prior to transplantation might safely be omitted in many patients. They should be maintained in highly immunized patients, however, for whom assignment of all C1q-positive antibodies as unacceptable antigens could lead to a significant delay or even prevention of transplantation.
Language	English
Publishing date	2017-03
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1160846-8
ISSN	1878-5492 ; 0966-3274
ISSN (online)	1878-5492
ISSN	0966-3274
DOI	10.1016/j.trim.2017.01.001
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Zs.A 3784: Show issues

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Article ; Online: Impact of perioperative blood transfusions on postoperative renal function and survival after resection of colorectal liver metastases.

Rodieck, Wiebke / Hallensleben, Michael / Robert, Julia / Beetz, Oliver / Grannas, Gerrit / Cammann, Sebastian / Oldhafer, Felix / Klempnauer, Juergen / Vondran, Florian W R / Kulik, Ulf

World journal of surgical oncology

2022 Volume 20, Issue 1, Page(s) 100

Abstract: Background and aims: Recent studies focusing on thoracic surgery suggest postoperative kidney injury depending on the amount of perioperative blood transfusions. Data investigating similar effects after resection of colorectal liver metastases (CRLM) ... ...

Abstract	Background and aims: Recent studies focusing on thoracic surgery suggest postoperative kidney injury depending on the amount of perioperative blood transfusions. Data investigating similar effects after resection of colorectal liver metastases (CRLM) are not available. Aim of this study was therefore to evaluate the influence of perioperative blood transfusions on postoperative renal function and survival after resection of CRLM. Methods: Seven hundred twenty-seven cases of liver resection for CRLM were retrospectively analyzed. Renal function was measured via estimated glomerular filtration rate (eGFR) and a postoperative decline of ≥ 10% was considered substantial. Potential influences on postoperative kidney function were assessed using univariable and multivariable logistic regression analyses. Cox-regression analyses were performed to estimate the impact on overall survival (OS). Results: Preoperative impaired kidney function (p = 0.001, OR 2.477) and transfusion of > 2 units of packed red blood cells (PRBC) (p = 0.046; OR 1.638) were independently associated with an increased risk for ≥ 10% loss of renal function. Neither a pre-existing renal impairment, nor the additional loss of renal function were associated with reduced survival. Chemotherapies in the context of primary colorectal cancer treatment (p = 0.002), age > 70 years at liver resection (p = 0.005), number (p = 0.001), and size of metastases > 50 mm (p = 0.018), duration of resection > 120 min (p = 0.006) and transfusions of > 2 units of PRBC (p = 0.039) showed a negative independent influence on OS. Conclusion: The results demonstrate a negative impact of perioperative blood transfusions on the postoperative renal function and OS. Hence, efforts to reduce blood transfusions should be intensified.
MeSH term(s)	Aged ; Blood Transfusion ; Colorectal Neoplasms/pathology ; Colorectal Neoplasms/surgery ; Humans ; Kidney/pathology ; Kidney/physiology ; Liver Neoplasms/secondary ; Retrospective Studies
Language	English
Publishing date	2022-03-30
Publishing country	England
Document type	Journal Article
ZDB-ID	2118383-1
ISSN	1477-7819 ; 1477-7819
ISSN (online)	1477-7819
ISSN	1477-7819
DOI	10.1186/s12957-022-02559-5
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Article ; Online: Non-invasive screening for subclinical liver graft injury in adults via donor-specific anti-HLA antibodies.

Höfer, Anne / Jonigk, Danny / Hartleben, Björn / Verboom, Murielle / Hallensleben, Michael / Manns, Michael P / Jaeckel, Elmar / Taubert, Richard

Scientific reports

2020 Volume 10, Issue 1, Page(s) 14242

Abstract: The majority of liver grafts exhibit abnormal histological findings late after transplantation, even when liver enzymes are normal. Such subclinical graft injuries were associated with rejection and fibrosis progression in recent studies. The ... ...

Abstract	The majority of liver grafts exhibit abnormal histological findings late after transplantation, even when liver enzymes are normal. Such subclinical graft injuries were associated with rejection and fibrosis progression in recent studies. The identification of non-invasive biomarkers for subclinical graft injury might help to individualize immunosuppression. Therefore, graft injury was assessed in 133 liver biopsies with normal/near normal liver enzymes from a prospective liver biopsy program. Cytokeratin-18 cell death marker (M65) and donor specific anti-HLA antibodies (DSA) were measured as non-invasive markers in paired plasma samples in addition to routine parameters. M65 was associated with subclinical graft injury but this association was too weak for reasonable clinical application. DSA positivity was associated with more graft inflammation (OR = 5.4) and more fibrosis (OR = 4.2). Absence of DSA excluded fibrosis in 87-89%, while presence of DSA excluded histological criteria for immunosuppression minimization attempts in 92-97%. While CK18 cell death marker had no diagnostic value for the detection of subclinical liver graft injury, DSA testing can help to preselect patients for immunosuppression reduction in case of DSA negativity, while DSA positivity should prompt elastography or liver biopsy for the assessment of subclinical graft injury.
MeSH term(s)	Adult ; Aged ; Allografts/pathology ; Biomarkers/blood ; Biopsy ; Female ; Graft Rejection/immunology ; Graft Survival ; HLA Antigens/immunology ; Humans ; Immunosuppression ; Isoantibodies/immunology ; Keratin-18/analysis ; Keratin-18/blood ; Keratin-18/immunology ; Liver/pathology ; Liver Transplantation/methods ; Male ; Middle Aged ; Peptide Fragments/immunology ; Retrospective Studies ; Tissue Donors ; Young Adult
Chemical Substances	Biomarkers ; HLA Antigens ; Isoantibodies ; Keratin-18 ; M65 antigen, human ; Peptide Fragments
Language	English
Publishing date	2020-08-28
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-020-70938-7
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Article ; Online: DSA Are Associated With More Graft Injury, More Fibrosis, and Upregulation of Rejection-associated Transcripts in Subclinical Rejection.

Höfer, Anne / Jonigk, Danny / Hartleben, Björn / Verboom, Murielle / Hallensleben, Michael / Hübscher, Stefan G / Manns, Michael P / Jaeckel, Elmar / Taubert, Richard

Transplantation

2019 Volume 104, Issue 3, Page(s) 551–561

Abstract: Background: Subclinical T cell-mediated rejection (subTCMR) is commonly found after liver transplantation and has a good short-term prognosis, even when it is left untreated. Donor-specific antibodies (DSA) are putatively associated with a worse ... ...

Abstract	Background: Subclinical T cell-mediated rejection (subTCMR) is commonly found after liver transplantation and has a good short-term prognosis, even when it is left untreated. Donor-specific antibodies (DSA) are putatively associated with a worse prognosis for recipient and graft after liver transplantation. Methods: To assess the immune regulation in subTCMR grafts, gene expression of 93 transcripts for graft injury, tolerance, and immune regulation was analyzed in 77 biopsies with "no histologic rejection" (NHR; n = 25), "clinical TCMR" (cTMCR; n = 16), and subTCMR (n = 36). In addition, all available subTCMR biopsies (n = 71) were tested for DSA with bead assays. Results: SubTCMR showed heterogeneous and intermediate expression profiles of transcripts that were upregulated in cTCMR. Graft gene expression suggested a lower activation of effector lymphocytes and a higher activation of regulatory T cells in grafts with subTCMR compared to cTCMR. DSA positivity in subTCMR was associated with histological evidence of more severe graft inflammation and fibrosis. This more severe DSA+ associated graft injury in subTCMR was converged with an upregulation of cTCMR-associated transcripts. In nonsupervised analysis, DSA positive subTCMR mostly clustered together with cTCMR, while DSA negative subTCMR clustered together with NHR. Conclusions: T cell-mediated rejection seems to form a continuum of alloimmune activation. Although subTCMR exhibited less expression of TCMR-associated transcript, DSA positivity in subTCMR was associated with an upregulation of rejection-associated transcripts. The identification of DSA positive subclinical rejection might help to define patients with more inflammation in the graft and development of fibrosis.
MeSH term(s)	Adolescent ; Adult ; Aged ; Allografts/cytology ; Allografts/immunology ; Allografts/pathology ; Biopsy ; Female ; Fibrosis ; Gene Expression Profiling ; Graft Rejection/diagnosis ; Graft Rejection/immunology ; Graft Rejection/pathology ; Histocompatibility ; Humans ; Isoantibodies/analysis ; Isoantibodies/immunology ; Liver/cytology ; Liver/immunology ; Liver/pathology ; Liver Transplantation/adverse effects ; Male ; Middle Aged ; Prospective Studies ; T-Lymphocytes, Cytotoxic/immunology ; T-Lymphocytes, Cytotoxic/metabolism ; T-Lymphocytes, Regulatory/immunology ; T-Lymphocytes, Regulatory/metabolism ; Up-Regulation ; Young Adult
Chemical Substances	Isoantibodies
Language	English
Publishing date	2019-10-25
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	208424-7
ISSN	1534-6080 ; 0041-1337
ISSN (online)	1534-6080
ISSN	0041-1337
DOI	10.1097/TP.0000000000003034
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Zs.A 488: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 509: Show issues

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Article ; Online: Lung transplantation despite preformed donor-specific antihuman leukocyte antigen antibodies: a 9-year single-center experience.

American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons

2023 Volume 23, Issue 11, Page(s) 1740–1756

Abstract: Pretransplant allosensitization to human leukocyte antigens (HLA) increases the recipient's waiting list time and mortality in lung transplantation. Rather than waiting for crossmatch-negative donors, since 2013, recipients with preformed donor-specific ... ...

Abstract	Pretransplant allosensitization to human leukocyte antigens (HLA) increases the recipient's waiting list time and mortality in lung transplantation. Rather than waiting for crossmatch-negative donors, since 2013, recipients with preformed donor-specific antiHLA antibodies (pfDSA) have been managed with repeated IgA- and IgM-enriched intravenous immunoglobulin (IgGAM) infusions, usually in combination with plasmapheresis before IgGAM and a single dose of antiCD20 antibody. This retrospective study presents our 9-year experience with patients transplanted with pfDSA. Records of patients transplanted between February 2013 and May 2022 were reviewed. Outcomes were compared between patients with pfDSA and those without any de novo donor-specific antiHLA antibodies. The median follow-up time was 50 months. Of the 1,043 patients who had undergone lung transplantation, 758 (72.7%) did not develop any early donor-specific antiHLA antibodies, and 62 (5.9%) patients exhibited pfDSA. Among the 52 (84%) patients who completed treatment, pfDSA was cleared in 38 (73%). In pfDSA vs control patients and at 8-year follow-up, respectively, graft survival (%) was 75 vs 65 (P = .493) and freedom from chronic lung allograft dysfunction (%) was 63 vs 65 (P = .525). In lung transplantation, crossing the preformed HLA-antibody barrier is safe using a treatment protocol based on IgGAM. Patients with pfDSA have a good 8-year graft survival rate and freedom from chronic lung allograft dysfunction, similar to control patients.
MeSH term(s)	Humans ; Retrospective Studies ; Antibodies ; Tissue Donors ; Lung Transplantation ; HLA Antigens ; Graft Rejection/etiology ; Graft Survival ; Histocompatibility Testing
Chemical Substances	Antibodies ; HLA Antigens
Language	English
Publishing date	2023-05-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2060594-8
ISSN	1600-6143 ; 1600-6135
ISSN (online)	1600-6143
ISSN	1600-6135
DOI	10.1016/j.ajt.2023.04.034
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