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Generation of Unexpected Allele-Specific Anti-HLA Antibodies after the Transplantation of a Fully-Matched Kidney Allograft and the Diagnostic Approaches Required for Excluding Harmful Effects after Subsequent Renal Regrafts

Schlaf, Gerald ; Tissue Typing Laboratory (GHATT), University Hospital Halle/Saale, Ernst-Grube-Straße 20, 06120 Halle/Saale, Germany ; Kehlen, Jakob ; [et al.]

LIDSEN Publishing Inc ; 2021

In: OBM Transplantation Vol. 05, No. 02 ( 2021-01-26), p. 1-1

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In: OBM Transplantation, LIDSEN Publishing Inc, Vol. 05, No. 02 ( 2021-01-26), p. 1-1

Abstract: The specification of anti-human leukocyte antigen (HLA) antibodies is an important task for patients awaiting kidney allografts. Especially the patients immunized in previous transplantations, transfusions, or pregnancies must be carefully observed, since grafting patients with HLA antigens/phenotypes recognized by their pre-formed antibodies are the main cause of harmful hyperacute and acute rejection. The complement-dependent lymphocytotoxicity-based de facto (physical) crossmatching (CDC-CM) has thus been implemented as the last diagnostic obstacle before kidney allografting. Here, an assay is performed by incubating the donors’ lymphocytes with the sera of the prospective recipients, and a negative outcome was desired for eligibility of the underlying organ allocation. Furthermore, valid antibody specification has to be performed at least quarterly for each patient on the kidney waiting list, as defined by certain guidelines, for example, the Eurotransplant guidelines. Based on the exclusion of these specificities, also referred to as virtual crossmatching, certain donors are a priori listed as unacceptable for these recipients. In this case report, we showed that defining unacceptable antigens may be difficult if the recipients’ antibodies are allele-specific after being generated in the patient who is expressing the HLA-class II antigen DQ6 and also developing antibodies against this antigen. Low resolution (two-digit) typing is used before kidney allografting. Thus, these antibodies are generally not definable, as donors and recipients share the same antigen (allelic group). Here, we demonstrate the diagnostic approaches required to exclude inadequate kidney donors for a patient exhibiting antibodies only against the HLA-DQB1*06:04 allelic variant and not against the common phenotype HLA-DQ6. In practice, the patient’s HLA-class II high resolution (four-digit) typing, as well as his antibody specification at the highest (single antigen) resolution, are included. Furthermore, we critically discuss, according to the Eurotransplant guidelines, the missing possibility to declare own HLA-antigens unacceptable, which may be very helpful for recipients who exhibit allele-specific antibodies.

Type of Medium: Online Resource

ISSN: 2577-5820

URL: Issue

URL: Journal

URL: Article

DOI: 10.21926/obm.transplant.2102

DOI: 10.21926/obm.transplant.

DOI: 10.21926/obm.transplant.2102142

Language: Unknown

Publisher: LIDSEN Publishing Inc

Publication Date: 2021

detail.hit.zdb_id: 3010025-2

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Feasibility and early clinical impact of precision medicine for late-stage cancer patients in a regional public academic hospital

Ladekarl, Morten ; Nøhr, Anne Krogh ; Sønderkær, Mads ; [et al.]

Informa UK Limited ; 2023

In: Acta Oncologica Vol. 62, No. 3 ( 2023-03-04), p. 261-271

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In: Acta Oncologica, Informa UK Limited, Vol. 62, No. 3 ( 2023-03-04), p. 261-271

Type of Medium: Online Resource

ISSN: 0284-186X , 1651-226X

URL: Article

DOI: 10.1080/0284186X.2023.2185542

Language: English

Publisher: Informa UK Limited

Publication Date: 2023

detail.hit.zdb_id: 1492623-4

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4th Pediatric Allergy and Asthma Meeting (PAAM)

Yavuz, S. Tolga ; the Bilastine Pediatric Safety Study Group ; Koc, Ozan ; [et al.]

Wiley ; 2016

In: Clinical and Translational Allergy Vol. 6, No. S1 ( 2016-11)

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In: Clinical and Translational Allergy, Wiley, Vol. 6, No. S1 ( 2016-11)

Type of Medium: Online Resource

ISSN: 2045-7022

URL: Article

DOI: 10.1186/s13601-016-0117-8

Language: English

Publisher: Wiley

Publication Date: 2016

detail.hit.zdb_id: 2630865-4

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Kinship-based social inequality in Bronze Age Europe

Mittnik, Alissa ; Massy, Ken ; Knipper, Corina ; [et al.]

American Association for the Advancement of Science (AAAS) ; 2019

In: Science Vol. 366, No. 6466 ( 2019-11-08), p. 731-734

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In: Science, American Association for the Advancement of Science (AAAS), Vol. 366, No. 6466 ( 2019-11-08), p. 731-734

Abstract: Revealing and understanding the mechanisms behind social inequality in prehistoric societies is a major challenge. By combining genome-wide data, isotopic evidence, and anthropological and archaeological data, we have gone beyond the dominating supraregional approaches in archaeogenetics to shed light on the complexity of social status, inheritance rules, and mobility during the Bronze Age. We applied a deep microregional approach and analyzed genome-wide data of 104 human individuals deriving from farmstead-related cemeteries from the Late Neolithic to the Middle Bronze Age in southern Germany. Our results reveal individual households, lasting several generations, that consisted of a high-status core family and unrelated low-status individuals; a social organization accompanied by patrilocality and female exogamy; and the stability of this system over 700 years.

Type of Medium: Online Resource

ISSN: 0036-8075 , 1095-9203

URL: Article

DOI: 10.1126/science.aax6219

RVK:

TA 1000

RVK:

WA 15000

Language: English

Publisher: American Association for the Advancement of Science (AAAS)

Publication Date: 2019

detail.hit.zdb_id: 128410-1

detail.hit.zdb_id: 2066996-3

detail.hit.zdb_id: 2060783-0

SSG: 11

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Meta-analysis identifies seven susceptibility loci involved in the atopic march

Marenholz, Ingo ; Esparza-Gordillo, Jorge ; Rüschendorf, Franz ; [et al.]

Springer Science and Business Media LLC ; 2015

In: Nature Communications Vol. 6, No. 1 ( 2015-11-06)

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In: Nature Communications, Springer Science and Business Media LLC, Vol. 6, No. 1 ( 2015-11-06)

Abstract: Eczema often precedes the development of asthma in a disease course called the ‘atopic march’. To unravel the genes underlying this characteristic pattern of allergic disease, we conduct a multi-stage genome-wide association study on infantile eczema followed by childhood asthma in 12 populations including 2,428 cases and 17,034 controls. Here we report two novel loci specific for the combined eczema plus asthma phenotype, which are associated with allergic disease for the first time; rs9357733 located in EFHC1 on chromosome 6p12.3 (OR 1.27; P= 2.1 × 10 −8 ) and rs993226 between TMTC2 and SLC6A15 on chromosome 12q21.3 (OR 1.58; P= 5.3 × 10 −9 ). Additional susceptibility loci identified at genome-wide significance are FLG (1q21.3), IL4/KIF3A (5q31.1), AP5B1/OVOL1 (11q13.1), C11orf30/LRRC32 (11q13.5) and IKZF3 (17q21). We show that predominantly eczema loci increase the risk for the atopic march. Our findings suggest that eczema may play an important role in the development of asthma after eczema.

Type of Medium: Online Resource

ISSN: 2041-1723

URL: Article

DOI: 10.1038/ncomms9804

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2015

detail.hit.zdb_id: 2553671-0

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Utilization of complementary and alternative medicine (CAM) by women with breast cancer or gynecological cancer

Stöcker, Anja ; Mehnert-Theuerkauf, Anja ; Hinz, Andreas ; [et al.]

Public Library of Science (PLoS) ; 2023

In: PLOS ONE Vol. 18, No. 5 ( 2023-5-12), p. e0285718-

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In: PLOS ONE, Public Library of Science (PLoS), Vol. 18, No. 5 ( 2023-5-12), p. e0285718-

Abstract: Complementary and Alternative Medicine (CAM) has become increasingly popular among cancer patients. The prevalence of CAM use differs worldwide and depends on different sociodemographic and medical characteristics. Findings on predictors for CAM use and its benefits for quality of Life (QoL) have been inconclusive in recent studies. Objective The aim of the study was to determine the prevalence and methods of CAM use in breast cancer (BC) and gynecological cancer (GC) patients, to compare CAM users vs. non-CAM users regarding their sociodemographic and medical characteristics, and to investigate the relationship between CAM use and QoL. Methods In a sub-analysis from a multicenter, cross-sectional study in Germany, we examined 1,214 female cancer patients (897 with BC and 317 with GC). We obtained data from self-reports via standardized questionnaires and measured QoL with the EORTC QLQ-C30. Results In total, 565 of the 1,214 patients (46.5%) used some form of CAM. Its use was higher in BC than in GC patients (48.6% vs. 40.7%). In both cancer groups, the users evaluated CAM as being helpful (BC: 60.8%, GC: 59.6%) The most frequently used CAM methods were vitamins/minerals/micronutrients, homeopathy, and mistletoe therapy. CAM users are younger, more highly educated, and financially better off than non-CAM users. They are also characterized by having been diagnosed with cancer a longer time ago, being at more advanced stages of the disease, and experiencing higher distress levels. CAM use is significantly associated with a lower global health status/ QoL in GC patients. Predictors for CAM use are: high level of vocational education, middle or high monthly income, time span since diagnosis of more than 12 months, the status of currently ongoing chemotherapy or hormone therapy treatment, and distress. Conclusion Our data support the findings of previous studies and highlight the need to develop a consistent CAM definition with respect to comparability and evaluation of CAM services. More longitudinal studies are desirable to establish viable associations between CAM use and relevant outcomes such as QoL or disease management.

Type of Medium: Online Resource

ISSN: 1932-6203

URL: Article

DOI: 10.1371/journal.pone.0285718

DOI: 10.1371/journal.pone.0285718.g001

DOI: 10.1371/journal.pone.0285718.g002

DOI: 10.1371/journal.pone.0285718.g003

DOI: 10.1371/journal.pone.0285718.t001

DOI: 10.1371/journal.pone.0285718.t002

DOI: 10.1371/journal.pone.0285718.s001

DOI: 10.1371/journal.pone.0285718.r001

DOI: 10.1371/journal.pone.0285718.r002

DOI: 10.1371/journal.pone.0285718.r003

DOI: 10.1371/journal.pone.0285718.r004

Language: English

Publisher: Public Library of Science (PLoS)

Publication Date: 2023

detail.hit.zdb_id: 2267670-3

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Incorporating high-resolution climate, remote sensing and topographic data to map annual forest growth in central and eastern Europe

Jevšenak, Jernej ; Klisz, Marcin ; Mašek, Jiří ; [et al.]

Elsevier BV ; 2024

In: Science of The Total Environment Vol. 913 ( 2024-02), p. 169692-

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In: Science of The Total Environment, Elsevier BV, Vol. 913 ( 2024-02), p. 169692-

Type of Medium: Online Resource

ISSN: 0048-9697

URL: Article

DOI: 10.1016/j.scitotenv.2023.169692

RVK:

AR 10100

Language: English

Publisher: Elsevier BV

Publication Date: 2024

detail.hit.zdb_id: 1498726-0

detail.hit.zdb_id: 121506-1

SSG: 12

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Sense of coherence, resilience, and habitual optimism in cancer patients

Hinz, Andreas ; Schulte, Thomas ; Ernst, Jochen ; [et al.]

Elsevier BV ; 2023

In: International Journal of Clinical and Health Psychology Vol. 23, No. 2 ( 2023-04), p. 100358-

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In: International Journal of Clinical and Health Psychology, Elsevier BV, Vol. 23, No. 2 ( 2023-04), p. 100358-

Type of Medium: Online Resource

ISSN: 1697-2600

URL: Article

DOI: 10.1016/j.ijchp.2022.100358

Language: English

Publisher: Elsevier BV

Publication Date: 2023

detail.hit.zdb_id: 2208162-8

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Prevalence and Dynamics of BCR-ABL Independent Gene Mutations in Patients with Chronic Myeloid Leukemia

Ernst, Thomas ; Rinke, Jenny ; Busch, Melinda ; [et al.]

American Society of Hematology ; 2016

In: Blood Vol. 128, No. 22 ( 2016-12-02), p. 1221-1221

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In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 1221-1221

Abstract: Living without treatment has become a realistic target for patients with chronic myeloid leukemia (CML) who achieved durable deep molecular remission under treatment with tyrosine kinase inhibitors (TKI). Recently, we have identified novel BCR-ABL-independent gene mutations in newly diagnosed CML patients that may function as important cofactors in the evolution of CML and persistence of the disease (Schmidt M, Rinke J, et al. Leukemia 2014; 28(12): 2292-9). Here, we sought to investigate the dynamics of such mutations during a 2-year treatment with the second generation TKI nilotinib. To check if BCR-ABL independent mutations are an age associated phenomenon we also screened a cohort of children and adolescents with CML. A total of 51 chronic phase CML patients were analyzed including 31 adults (male, n=23; median age 57 years, range 42 to 73 years) and 20 children/adolescents (male, n= 14; median age 14 years, range 10 months to 27 years). For each adult patient, samples were analyzed at diagnosis, in subsequent complete cytogenetic remission (CCyR) after 3 months and in deep molecular remission (≤ MMR) after 24 months of nilotinib therapy. Children/adolescents samples were investigated at diagnosis only. Targeted deep next-generation sequencing (NGS) was used to analyze a panel of 30 commonly mutated genes in myeloid disorders. Constitutional DNA obtained from buccal swabs at diagnosis was investigated to check whether mutations are of somatic origin. BCR-ABL independent gene mutations were found in 8/31 (26%) adult CML patients at diagnosis affecting the genes ASXL1 (n=3), DNMT3A (n=3), RUNX1 (n=1) and RUNX1 plus TET2 (n=1). No mutation was recognized in corresponding constitutional DNA specimens indicating that all mutations were somatically acquired. Analysis of individual hematopoietic colonies from three adult patients revealed that most mutations were part of the BCR-ABL-positive clone. NGS of subsequent samples obtained after three months of TKI therapy identified two DNMT3A mutations in BCR-ABL-negative cells that were also present in BCR-ABL-positive cells at diagnosis, implying that this mutation preceded the BCR-ABL rearrangement. After 24 months of TKI treatment, NGS revealed these two DNMT3A mutations again as well as a novel low-level EZH2 mutation in a patient with deep molecular remission (MR4.5) that was neither detectable at diagnosis nor after 3 months of treatment indicating the emergence of a BCR-ABL-independent subclone in BCR-ABL-negative cells during long-term nilotinib treatment. Within the children/adolescents cohort BCR-ABL independent gene mutations were identified in 5/20 (25%) subjects all affecting the ASXL1 gene. All mutations were stop codon or frameshift mutations implying loss of ASXL1 gene function. We conclude that BCR-ABL independent gene mutations can be found frequently in CML patients and affect predominately epigenetic modifier genes. The finding of frequent mutations also in children/adolescents implicates that BCR-ABL independent gene mutations are not just age-related events. Such molecular aberrations may play an important role in the evolution and persistence of the disease and may affect therapy in both children and adults with CML. These findings may provide important novel genetic information regarding CML biology and for the design and performance of discontinuation trials. Disclosures Hochhaus: Novartis: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; BMS: Honoraria, Research Funding; ARIAD: Honoraria, Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V128.22.1221.1221

RVK:

XA 33000

RVK:

XA 10000

Language: English

Publisher: American Society of Hematology

Publication Date: 2016

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

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The molecular recognition of phosphatidic acid by an amphipathic helix in Opi1

Hofbauer, Harald F. ; Gecht, Michael ; Fischer, Sabine C. ; [et al.]

Rockefeller University Press ; 2018

In: Journal of Cell Biology Vol. 217, No. 9 ( 2018-09-03), p. 3109-3126

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In: Journal of Cell Biology, Rockefeller University Press, Vol. 217, No. 9 ( 2018-09-03), p. 3109-3126

Abstract: A key event in cellular physiology is the decision between membrane biogenesis and fat storage. Phosphatidic acid (PA) is an important intermediate at the branch point of these pathways and is continuously monitored by the transcriptional repressor Opi1 to orchestrate lipid metabolism. In this study, we report on the mechanism of membrane recognition by Opi1 and identify an amphipathic helix (AH) for selective binding of PA over phosphatidylserine (PS). The insertion of the AH into the membrane core renders Opi1 sensitive to the lipid acyl chain composition and provides a means to adjust membrane biogenesis. By rational design of the AH, we tune the membrane-binding properties of Opi1 and control its responsiveness in vivo. Using extensive molecular dynamics simulations, we identify two PA-selective three-finger grips that tightly bind the PA phosphate headgroup while interacting less intimately with PS. This work establishes lipid headgroup selectivity as a new feature in the family of AH-containing membrane property sensors.

Type of Medium: Online Resource

ISSN: 0021-9525 , 1540-8140

URL: Article

DOI: 10.1083/jcb.201802027

RVK:

WA 15000

Language: English

Publisher: Rockefeller University Press

Publication Date: 2018

detail.hit.zdb_id: 1421310-2

SSG: 12

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