Aina Teniente-Serra1,2,3, Berta Soldevila4, Bibiana Quirant-Sánchez1,2,3, Marco A Fernández5, Anna Ester Condins6, Manuel Puig-Domingo3,4, Ricardo Pujol-Borrell2,7, Eva M Martínez-Cáceres1,2,3. 1. Immunology Division, LCMN Germans Trias i Pujol University Hospital Badalona, Barcelona, Spain. 2. Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Barcelona, Spain. 3. Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Barcelona, Spain. 4. Endocrinology and Nutrition Department, Hospital Universitari Germans Trias i Pujol, Barcelona, Spain. 5. Flow Cytometry Facility, Germans Trias i Pujol Research Institute (IGTP), Barcelona, Spain. 6. Blood and Tissue Bank (BST), Barcelona, Spain. 7. Immunology Division, Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca, Barcelona, Spain.
Abstract
Background: Graves' disease (GD) is characterized by the production of autoantibodies against the TSHR (TRAbs). With long-term treatment, serum concentrations of TRAbs decline but in some patients, despite being clinically stable, TRAbs persist for many years.Objective: To investigate whether GD patients with persistence of TRAbs constitute a subset of patients that could be identified by phenotypic analysis of circulating lymphocytes, suggesting disease heterogeneity.Materials and methods: Peripheral blood lymphocytes (including naïve, memory and effector T and B cells, Th17, regulatory T cells (Treg), recent thymic emigrants (RTEs) and double positive CD4+CD8+ (DP) cells) were analysed by flow cytometry in a cross-sectional study in 25 clinically stable GD patients, five patients at onset of GD disease and 40 healthy donors (HDs). Results: GD patients with persistence of TRAbs showed a lower percentage of Treg and lower absolute numbers of central and effector memory CD8+ T cells than HD. No differences in RTEs were found in peripheral blood from GD patients compared to HD. Stable GD patients had higher percentage of DP cells of effector phenotype than HD.Conclusions: Using extensive phenotypic analysis of lymphocyte subpopulations, it is possible to detect changes that help to identify patients with persistent TSHR antibodies and may contribute to understand why the autoimmune response is maintained.
Background: Graves' disease (GD) is characterized by the production of autoantibodies against the TSHR (TRAbs). With long-term treatment, serum concentrations of TRAbs decline but in some patients, despite being clinically stable, TRAbs persist for many years.Objective: To investigate whether GDpatients with persistence of TRAbs constitute a subset of patients that could be identified by phenotypic analysis of circulating lymphocytes, suggesting disease heterogeneity.Materials and methods: Peripheral blood lymphocytes (including naïve, memory and effector T and B cells, Th17, regulatory T cells (Treg), recent thymic emigrants (RTEs) and double positive CD4+CD8+ (DP) cells) were analysed by flow cytometry in a cross-sectional study in 25 clinically stable GDpatients, five patients at onset of GD disease and 40 healthy donors (HDs). Results:GDpatients with persistence of TRAbs showed a lower percentage of Treg and lower absolute numbers of central and effector memory CD8+ T cells than HD. No differences in RTEs were found in peripheral blood from GDpatients compared to HD. Stable GDpatients had higher percentage of DP cells of effector phenotype than HD.Conclusions: Using extensive phenotypic analysis of lymphocyte subpopulations, it is possible to detect changes that help to identify patients with persistent TSHR antibodies and may contribute to understand why the autoimmune response is maintained.
Authors: Aina Teniente-Serra; Eduarda Pizarro; Bibiana Quirant-Sánchez; Marco A Fernández; Marta Vives-Pi; Eva M Martinez-Caceres Journal: Front Immunol Date: 2021-12-06 Impact factor: 7.561