Cluster analysis of flowcytometric immunophenotyping with extended T cell subsets in suspected immunodeficiency

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 analys...

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Main Authors: Luca Seitz, Daniel Gaitan, Caroline M. Berkemeier, Christoph T. Berger, Mike Recher
Format: Article
Language:English
Published: Wiley 2023-12-01
Series:Immunity, Inflammation and Disease
Subjects:
Online Access:https://doi.org/10.1002/iid3.1106
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author Luca Seitz
Daniel Gaitan
Caroline M. Berkemeier
Christoph T. Berger
Mike Recher
author_facet Luca Seitz
Daniel Gaitan
Caroline M. Berkemeier
Christoph T. Berger
Mike Recher
author_sort Luca Seitz
collection DOAJ
description 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.
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spelling doaj.art-9269f0808e1f427b9ae4da569e9fe4752023-12-29T08:52:36ZengWileyImmunity, Inflammation and Disease2050-45272023-12-011112n/an/a10.1002/iid3.1106Cluster analysis of flowcytometric immunophenotyping with extended T cell subsets in suspected immunodeficiencyLuca Seitz0Daniel Gaitan1Caroline M. Berkemeier2Christoph T. Berger3Mike Recher4Immunodeficiency Laboratory, Department of Biomedicine University Hospital Basel and University of Basel Basel SwitzerlandImmunodeficiency Laboratory, Department of Biomedicine University Hospital Basel and University of Basel Basel SwitzerlandDivision of Medical Immunology, Laboratory Medicine University Hospital Basel Basel SwitzerlandUniversity Center for Immunology University Hospital Basel Basel SwitzerlandImmunodeficiency Laboratory, Department of Biomedicine University Hospital Basel and University of Basel Basel SwitzerlandAbstract 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.https://doi.org/10.1002/iid3.1106cluster analysisflowcytometryinborn errors of immunityprimary immunodeficiencyT cell subsets
spellingShingle Luca Seitz
Daniel Gaitan
Caroline M. Berkemeier
Christoph T. Berger
Mike Recher
Cluster analysis of flowcytometric immunophenotyping with extended T cell subsets in suspected immunodeficiency
Immunity, Inflammation and Disease
cluster analysis
flowcytometry
inborn errors of immunity
primary immunodeficiency
T cell subsets
title Cluster analysis of flowcytometric immunophenotyping with extended T cell subsets in suspected immunodeficiency
title_full Cluster analysis of flowcytometric immunophenotyping with extended T cell subsets in suspected immunodeficiency
title_fullStr Cluster analysis of flowcytometric immunophenotyping with extended T cell subsets in suspected immunodeficiency
title_full_unstemmed Cluster analysis of flowcytometric immunophenotyping with extended T cell subsets in suspected immunodeficiency
title_short Cluster analysis of flowcytometric immunophenotyping with extended T cell subsets in suspected immunodeficiency
title_sort cluster analysis of flowcytometric immunophenotyping with extended t cell subsets in suspected immunodeficiency
topic cluster analysis
flowcytometry
inborn errors of immunity
primary immunodeficiency
T cell subsets
url https://doi.org/10.1002/iid3.1106
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