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Analysis of T cell repertoires of CD45RO CD4 T cells in cohorts of patients with bullous pemphigoid: A pilot study

Autoimmune diseases develop over years - starting from a subclinical phenotype to clinically manifest autoimmune disease. The factors that drive this transition are ill-defined. To predict the turning point towards clinical disease and to intervene in the progress of autoimmune-mediated dysfunction,...

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Autores principales: Niebuhr, Markus, Bahreini, Farbod, Fähnrich, Anke, Bomholt, Christina, Bieber, Katja, Schmidt, Enno, Ibrahim, Saleh, Hammers, Christoph M., Kalies, Kathrin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9706093/
https://www.ncbi.nlm.nih.gov/pubmed/36458004
http://dx.doi.org/10.3389/fimmu.2022.1006941
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author Niebuhr, Markus
Bahreini, Farbod
Fähnrich, Anke
Bomholt, Christina
Bieber, Katja
Schmidt, Enno
Ibrahim, Saleh
Hammers, Christoph M.
Kalies, Kathrin
author_facet Niebuhr, Markus
Bahreini, Farbod
Fähnrich, Anke
Bomholt, Christina
Bieber, Katja
Schmidt, Enno
Ibrahim, Saleh
Hammers, Christoph M.
Kalies, Kathrin
author_sort Niebuhr, Markus
collection PubMed
description Autoimmune diseases develop over years - starting from a subclinical phenotype to clinically manifest autoimmune disease. The factors that drive this transition are ill-defined. To predict the turning point towards clinical disease and to intervene in the progress of autoimmune-mediated dysfunction, the establishment of new biomarkers is needed. Especially CD4 T cells are crucially involved in autoimmunity: first, during the initiation phase, because they lose their tolerance towards self-peptides, and second, by the subsequent ongoing presentation of self-peptides during the active autoimmune disease. Accordingly, changes in the degree of diversity of T cell receptor (TCR) repertoires in autoimmunity have been reported. These findings led to the hypothesis that transition from pre-disease to autoimmune disease is associated with an increase of abnormally expanded T cell clones that occupy large portions of the TCR repertoire. In this pilot study, we asked whether the ratio and the diversity of the TCR repertoires of circulating memory (CD45RO) and naïve (CD45RA) CD4 T cells could serve as a predictive factor for the development of autoimmunity. To find out, we analyzed the TCRβ repertoires of memory and naïve CD4 T cells in a small cohort of four gender- and age-matched elderly patients having the autoimmune blistering disease bullous pemphigoid or non-melanoma skin cancers. We found that the extent of clonal expansions in the TCRβ repertoires from the circulating memory and naïve CD4 populations did not differ between the patient groups. This result shows that the diversity of TCR repertoires from peripheral CD4 T cells does not reflect the manifestation of the skin-associated autoimmune disease BP and does not qualify as a prognostic factor. We propose that longitudinal TCR repertoire analysis of younger patients might be more informative.
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spelling pubmed-97060932022-11-30 Analysis of T cell repertoires of CD45RO CD4 T cells in cohorts of patients with bullous pemphigoid: A pilot study Niebuhr, Markus Bahreini, Farbod Fähnrich, Anke Bomholt, Christina Bieber, Katja Schmidt, Enno Ibrahim, Saleh Hammers, Christoph M. Kalies, Kathrin Front Immunol Immunology Autoimmune diseases develop over years - starting from a subclinical phenotype to clinically manifest autoimmune disease. The factors that drive this transition are ill-defined. To predict the turning point towards clinical disease and to intervene in the progress of autoimmune-mediated dysfunction, the establishment of new biomarkers is needed. Especially CD4 T cells are crucially involved in autoimmunity: first, during the initiation phase, because they lose their tolerance towards self-peptides, and second, by the subsequent ongoing presentation of self-peptides during the active autoimmune disease. Accordingly, changes in the degree of diversity of T cell receptor (TCR) repertoires in autoimmunity have been reported. These findings led to the hypothesis that transition from pre-disease to autoimmune disease is associated with an increase of abnormally expanded T cell clones that occupy large portions of the TCR repertoire. In this pilot study, we asked whether the ratio and the diversity of the TCR repertoires of circulating memory (CD45RO) and naïve (CD45RA) CD4 T cells could serve as a predictive factor for the development of autoimmunity. To find out, we analyzed the TCRβ repertoires of memory and naïve CD4 T cells in a small cohort of four gender- and age-matched elderly patients having the autoimmune blistering disease bullous pemphigoid or non-melanoma skin cancers. We found that the extent of clonal expansions in the TCRβ repertoires from the circulating memory and naïve CD4 populations did not differ between the patient groups. This result shows that the diversity of TCR repertoires from peripheral CD4 T cells does not reflect the manifestation of the skin-associated autoimmune disease BP and does not qualify as a prognostic factor. We propose that longitudinal TCR repertoire analysis of younger patients might be more informative. Frontiers Media S.A. 2022-11-15 /pmc/articles/PMC9706093/ /pubmed/36458004 http://dx.doi.org/10.3389/fimmu.2022.1006941 Text en Copyright © 2022 Niebuhr, Bahreini, Fähnrich, Bomholt, Bieber, Schmidt, Ibrahim, Hammers and Kalies https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Niebuhr, Markus
Bahreini, Farbod
Fähnrich, Anke
Bomholt, Christina
Bieber, Katja
Schmidt, Enno
Ibrahim, Saleh
Hammers, Christoph M.
Kalies, Kathrin
Analysis of T cell repertoires of CD45RO CD4 T cells in cohorts of patients with bullous pemphigoid: A pilot study
title Analysis of T cell repertoires of CD45RO CD4 T cells in cohorts of patients with bullous pemphigoid: A pilot study
title_full Analysis of T cell repertoires of CD45RO CD4 T cells in cohorts of patients with bullous pemphigoid: A pilot study
title_fullStr Analysis of T cell repertoires of CD45RO CD4 T cells in cohorts of patients with bullous pemphigoid: A pilot study
title_full_unstemmed Analysis of T cell repertoires of CD45RO CD4 T cells in cohorts of patients with bullous pemphigoid: A pilot study
title_short Analysis of T cell repertoires of CD45RO CD4 T cells in cohorts of patients with bullous pemphigoid: A pilot study
title_sort analysis of t cell repertoires of cd45ro cd4 t cells in cohorts of patients with bullous pemphigoid: a pilot study
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9706093/
https://www.ncbi.nlm.nih.gov/pubmed/36458004
http://dx.doi.org/10.3389/fimmu.2022.1006941
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