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, 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 naive (CD45RA) CD4 T cells could serve as a predictive factor for the development of autoimmunity. To find out, we analyzed the TCR beta repertoires of memory and naive 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 TCR beta repertoires from the circulating memory and naive 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.

Automated summary

Autoimmune diseases develop gradually and the factors that drive this progression are not well defined. CD4 T cells play a crucial role in autoimmunity and changes in T cell receptor (TCR) repertoires have been reported in autoimmunity. This study aimed to investigate whether the diversity of TCR repertoires in CD4 T cells could predict the development of autoimmunity. The results showed that the extent of clonal expansions in the TCR beta repertoires did not differ between patient groups. The authors propose that longitudinal TCR repertoire analysis of younger patients might be more informative.