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  1. Article ; Online: Cluster analysis of flowcytometric immunophenotyping with extended T cell subsets in suspected immunodeficiency.

    Seitz, Luca / Gaitan, Daniel / Berkemeier, Caroline M / Berger, Christoph T / Recher, Mike

    Immunity, inflammation and disease

    2023  Volume 11, Issue 12, Page(s) e1106

    Abstract: Background: Patients with immunodeficiencies commonly experience diagnostic delays resulting in morbidity. There is an unmet need to identify patients earlier, especially those with high risk for complications. Compared to immunoglobulin quantification ... ...

    Abstract Background: Patients with immunodeficiencies commonly experience diagnostic delays resulting in morbidity. There is an unmet need to identify patients earlier, especially those with high risk for complications. Compared to immunoglobulin quantification and flowcytometric B cell subset analysis, expanded T cell subset analysis is rarely performed in the initial evaluation of patients with suspected immunodeficiency. The simultaneous interpretation of multiple immune variables, including lymphocyte subsets, is challenging.
    Objective: To evaluate the diagnostic value of cluster analyses of immune variables in patients with suspected immunodeficiency.
    Methods: Retrospective analysis of 38 immune system variables, including seven B cell and sixteen T cell subpopulations, in 107 adult patients (73 with immunodeficiency, 34 without) evaluated at a tertiary outpatient immunology clinic. Correlation analyses of individual variables, k-means cluster analysis with evaluation of the classification into "no immunodeficiency" versus "immunodeficiency" and visual analyses of hierarchical heatmaps were performed.
    Results: Binary classification of patients into groups with and without immunodeficiency was correct in 54% of cases with the full data set and increased to 69% and 75% of cases, respectively, when only 16 variables with moderate (p < .05) or 7 variables with strong evidence (p < .01) for a difference between groups were included. In a cluster heatmap with all patients but only moderately differing variables and a heatmap with only immunodeficient patients restricted to T cell variables alone, segregation of most patients with common variable immunodeficiency and combined immunodeficiency was observed.
    Conclusion: Cluster analyses of immune variables, including detailed lymphocyte flowcytometry with T cell subpopulations, may support clinical decision making for suspected immunodeficiency in daily practice.
    MeSH term(s) Adult ; Humans ; Immunophenotyping ; Retrospective Studies ; T-Lymphocyte Subsets ; B-Lymphocytes ; Common Variable Immunodeficiency
    Language English
    Publishing date 2023-08-09
    Publishing country England
    Document type Journal Article
    ZDB-ID 2740382-8
    ISSN 2050-4527 ; 2050-4527
    ISSN (online) 2050-4527
    ISSN 2050-4527
    DOI 10.1002/iid3.1106
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Post-transplant Inflammatory Bowel Disease Associated with Donor-Derived TIM-3 Deficiency.

    Baldrich, Adrian / Althaus, Dominic / Menter, Thomas / Hirsiger, Julia R / Köppen, Julius / Hupfer, Robin / Juskevicius, Darius / Konantz, Martina / Bosch, Angela / Drexler, Beatrice / Gerull, Sabine / Ghosh, Adhideb / Meyer, Benedikt J / Jauch, Annaise / Pini, Katia / Poletti, Fabio / Berkemeier, Caroline M / Heijnen, Ingmar / Panne, Isabelle /
    Cavelti-Weder, Claudia / Niess, Jan Hendrik / Dixon, Karen / Daikeler, Thomas / Hartmann, Karin / Hess, Christoph / Halter, Jörg / Passweg, Jakob / Navarini, Alexander A / Yamamoto, Hiroyuki / Berger, Christoph T / Recher, Mike / Hruz, Petr

    Journal of clinical immunology

    2024  Volume 44, Issue 3, Page(s) 63

    Abstract: Inflammatory bowel disease (IBD) occurring following allogeneic stem cell transplantation (aSCT) is a very rare condition. The underlying pathogenesis needs to be better defined. There is currently no systematic effort to exclude loss- or gain-of- ... ...

    Abstract Inflammatory bowel disease (IBD) occurring following allogeneic stem cell transplantation (aSCT) is a very rare condition. The underlying pathogenesis needs to be better defined. There is currently no systematic effort to exclude loss- or gain-of-function mutations in immune-related genes in stem cell donors. This is despite the fact that more than 100 inborn errors of immunity may cause or contribute to IBD. We have molecularly characterized a patient who developed fulminant inflammatory bowel disease following aSCT with stable 100% donor-derived hematopoiesis. A pathogenic c.A291G; p.I97M HAVCR2 mutation encoding the immune checkpoint protein TIM-3 was identified in the patient's blood-derived DNA, while being absent in DNA derived from the skin. TIM-3 expression was much decreased in the patient's serum, and in vitro-activated patient-derived T cells expressed reduced TIM-3 levels. In contrast, T cell-intrinsic CD25 expression and production of inflammatory cytokines were preserved. TIM-3 expression was barely detectable in the immune cells of the patient's intestinal mucosa, while being detected unambiguously in the inflamed and non-inflamed colon from unrelated individuals. In conclusion, we report the first case of acquired, "transplanted" insufficiency of the regulatory TIM-3 checkpoint linked to post-aSCT IBD.
    MeSH term(s) Humans ; Cytokines/metabolism ; Hepatitis A Virus Cellular Receptor 2/genetics ; Inflammatory Bowel Diseases/diagnosis ; Inflammatory Bowel Diseases/etiology ; Intestinal Mucosa ; Stem Cell Transplantation/adverse effects
    Chemical Substances Cytokines ; Hepatitis A Virus Cellular Receptor 2
    Language English
    Publishing date 2024-02-16
    Publishing country Netherlands
    Document type Case Reports ; Journal Article
    ZDB-ID 779361-3
    ISSN 1573-2592 ; 0271-9142
    ISSN (online) 1573-2592
    ISSN 0271-9142
    DOI 10.1007/s10875-024-01667-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Co-Occurrence of ANCA-Associated Vasculitis and Sjögren's Syndrome in a Patient With Acromegaly: A Case Report and Retrospective Single-Center Review of Acromegaly Patients.

    Fuchs, Philipp S / Lötscher, Jonas / Berkemeier, Caroline M / Hirsiger, Julia R / Ghosh, Adhideb / Li, Quan-Zhen / Deigendesch, Nikolaus / Christ, Emanuel / Navarini, Alexander A / Recher, Mike / Daikeler, Thomas / Heijnen, Ingmar A F M / Berger, Christoph T

    Frontiers in immunology

    2020  Volume 11, Page(s) 613130

    Abstract: Background: ANCA-associated vasculitis (AAV) and Sjögren's syndrome (SS) are uncommon autoimmune diseases. The co-occurrence in the same patient has been rarely described. Acromegaly has been associated with autoimmune thyroiditis, but the prevalence of ...

    Abstract Background: ANCA-associated vasculitis (AAV) and Sjögren's syndrome (SS) are uncommon autoimmune diseases. The co-occurrence in the same patient has been rarely described. Acromegaly has been associated with autoimmune thyroiditis, but the prevalence of other autoimmune disorders such as AAV and SS has not been evaluated in acromegaly.
    Methods: Characterization of a patient with acromegaly and two rare autoimmune diseases-SS and AAV (microscopic polyangiitis (MPA))-by autoantibody-array and whole exome sequencing (WES). Single-center retrospective review of medical records of acromegaly patients to explore the prevalence of diagnosed autoimmune diseases.
    Results: We report a Caucasian woman in her 50's with a serologically (anti-SSA/Ro, anti-MPO-ANCA antibodies) and histologically confirmed diagnosis of symptomatic SS and MPA. SS with MPO-ANCA positivity preceded MPA. An exploratory autoantigen array detected a broad spectrum of autoantibodies. WES revealed heterozygous carrier status of the PTPN22 mutation R620W, which is associated with an increased risk for autoimmunity. A similar combination of positive anti-SSA/Ro autoantibodies and ANCA was only present in 5/1184 (0.42%) other patients tested for both antibodies in our clinic over six years. Amongst 85 acromegaly patients seen at our clinic in a 20-year period, 12% had a clinically relevant associated immunological disease.
    Conclusion: We present a rare case of SS and AAV in a patient with acromegaly and multiple autoantibody specificities. Patients with SS and ANCA should be closely monitored for the development of (subclinical) AAV. Whether acromegaly represents a risk for autoimmunity should be further investigated in prospective acromegaly cohorts.
    MeSH term(s) Acromegaly/immunology ; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/immunology ; Antibodies, Antineutrophil Cytoplasmic/immunology ; Autoantibodies/immunology ; Female ; Humans ; Middle Aged ; Retrospective Studies ; Sjogren's Syndrome/immunology
    Chemical Substances Antibodies, Antineutrophil Cytoplasmic ; Autoantibodies
    Language English
    Publishing date 2020-12-21
    Publishing country Switzerland
    Document type Case Reports ; 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.2020.613130
    Database MEDical Literature Analysis and Retrieval System OnLINE

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