Lower expression levels of the programmed death 1 receptor on CD4+CD25+ T cells and correlation with the PD‐1.3A genotype in patients with systemic lupus erythematosus

Abstract Objective A genetic polymorphism in the programmed death 1 (PD‐1) gene encoding the coinhibitory PD‐1 immunoreceptor, PD‐1.3A, is associated with systemic lupus erythematosus (SLE). The aim of this study was to assess PD‐1 receptor expression in patients with SLE, in comparison with relativ...

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Published in:Arthritis & Rheumatism
Main Authors: Kristjansdottir, Helga, Steinsson, Kristjan, Gunnarsson, Iva, Gröndal, Gerdur, Erlendsson, Kristjan, Alarcón‐Riquelme, Marta E.
Format: Article in Journal/Newspaper
Language:English
Published: Wiley 2010
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Online Access:http://dx.doi.org/10.1002/art.27417
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spelling crwiley:10.1002/art.27417 2024-06-23T07:54:09+00:00 Lower expression levels of the programmed death 1 receptor on CD4+CD25+ T cells and correlation with the PD‐1.3A genotype in patients with systemic lupus erythematosus Kristjansdottir, Helga Steinsson, Kristjan Gunnarsson, Iva Gröndal, Gerdur Erlendsson, Kristjan Alarcón‐Riquelme, Marta E. 2010 http://dx.doi.org/10.1002/art.27417 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fart.27417 https://onlinelibrary.wiley.com/doi/pdf/10.1002/art.27417 en eng Wiley http://onlinelibrary.wiley.com/termsAndConditions#vor Arthritis & Rheumatism volume 62, issue 6, page 1702-1711 ISSN 0004-3591 1529-0131 journal-article 2010 crwiley https://doi.org/10.1002/art.27417 2024-06-06T04:21:16Z Abstract Objective A genetic polymorphism in the programmed death 1 (PD‐1) gene encoding the coinhibitory PD‐1 immunoreceptor, PD‐1.3A, is associated with systemic lupus erythematosus (SLE). The aim of this study was to assess PD‐1 receptor expression in patients with SLE, in comparison with relatives and unrelated healthy controls, and to identify correlations of lower expression levels of PD‐1 receptor with the PD‐1.3A genotype. Methods Patients with SLE, patients' relatives, and unrelated healthy control subjects from Iceland and Sweden were studied. Peripheral blood mononuclear cells (PBMCs) were stimulated with anti‐CD3/anti‐CD28, and PD‐1 expression was analyzed by flow cytometry. PD‐1.3A/G genotyping was performed using polymerase chain reaction–restriction fragment length polymorphism analysis. Results PD‐1 expression on PBMCs was induced after antibody stimulation, showing increases of 2.1‐fold in SLE patients, 3.1‐fold in relatives, and 5.1‐fold in healthy controls. The frequency of PD‐1+ cells was significantly lower in SLE patients compared with relatives and healthy controls. PD‐1 expression on PD‐1+ cells and on CD4+CD25+ T cells was significantly lower in SLE patients and relatives compared with healthy controls. PD‐1 expression was significantly elevated on CD25 high cells. Levels of PD‐1 expression on CD25 high and CD25 intermediate cells were significantly lower in SLE patients compared with healthy controls. PD‐1 was expressed on both FoxP3− and FoxP3+ cells. Lower expression of PD‐1 was significantly correlated with the PD‐1.3A/G genotype. Conclusion The results demonstrate significantly lower PD‐1 receptor expression in SLE patients and their relatives and reveal a significant correlation of lower PD‐1 expression with the PD‐1.3A allele. Thus, PD‐1.3A may contribute to abnormalities in PD‐1 receptor expression on CD4+CD25+ T cells in patients with SLE, providing support for an important role of the PD‐1 pathway in SLE and, possibly, in other autoimmune diseases. Article in Journal/Newspaper Iceland Wiley Online Library Arthritis & Rheumatism 62 6 1702 1711
institution Open Polar
collection Wiley Online Library
op_collection_id crwiley
language English
description Abstract Objective A genetic polymorphism in the programmed death 1 (PD‐1) gene encoding the coinhibitory PD‐1 immunoreceptor, PD‐1.3A, is associated with systemic lupus erythematosus (SLE). The aim of this study was to assess PD‐1 receptor expression in patients with SLE, in comparison with relatives and unrelated healthy controls, and to identify correlations of lower expression levels of PD‐1 receptor with the PD‐1.3A genotype. Methods Patients with SLE, patients' relatives, and unrelated healthy control subjects from Iceland and Sweden were studied. Peripheral blood mononuclear cells (PBMCs) were stimulated with anti‐CD3/anti‐CD28, and PD‐1 expression was analyzed by flow cytometry. PD‐1.3A/G genotyping was performed using polymerase chain reaction–restriction fragment length polymorphism analysis. Results PD‐1 expression on PBMCs was induced after antibody stimulation, showing increases of 2.1‐fold in SLE patients, 3.1‐fold in relatives, and 5.1‐fold in healthy controls. The frequency of PD‐1+ cells was significantly lower in SLE patients compared with relatives and healthy controls. PD‐1 expression on PD‐1+ cells and on CD4+CD25+ T cells was significantly lower in SLE patients and relatives compared with healthy controls. PD‐1 expression was significantly elevated on CD25 high cells. Levels of PD‐1 expression on CD25 high and CD25 intermediate cells were significantly lower in SLE patients compared with healthy controls. PD‐1 was expressed on both FoxP3− and FoxP3+ cells. Lower expression of PD‐1 was significantly correlated with the PD‐1.3A/G genotype. Conclusion The results demonstrate significantly lower PD‐1 receptor expression in SLE patients and their relatives and reveal a significant correlation of lower PD‐1 expression with the PD‐1.3A allele. Thus, PD‐1.3A may contribute to abnormalities in PD‐1 receptor expression on CD4+CD25+ T cells in patients with SLE, providing support for an important role of the PD‐1 pathway in SLE and, possibly, in other autoimmune diseases.
format Article in Journal/Newspaper
author Kristjansdottir, Helga
Steinsson, Kristjan
Gunnarsson, Iva
Gröndal, Gerdur
Erlendsson, Kristjan
Alarcón‐Riquelme, Marta E.
spellingShingle Kristjansdottir, Helga
Steinsson, Kristjan
Gunnarsson, Iva
Gröndal, Gerdur
Erlendsson, Kristjan
Alarcón‐Riquelme, Marta E.
Lower expression levels of the programmed death 1 receptor on CD4+CD25+ T cells and correlation with the PD‐1.3A genotype in patients with systemic lupus erythematosus
author_facet Kristjansdottir, Helga
Steinsson, Kristjan
Gunnarsson, Iva
Gröndal, Gerdur
Erlendsson, Kristjan
Alarcón‐Riquelme, Marta E.
author_sort Kristjansdottir, Helga
title Lower expression levels of the programmed death 1 receptor on CD4+CD25+ T cells and correlation with the PD‐1.3A genotype in patients with systemic lupus erythematosus
title_short Lower expression levels of the programmed death 1 receptor on CD4+CD25+ T cells and correlation with the PD‐1.3A genotype in patients with systemic lupus erythematosus
title_full Lower expression levels of the programmed death 1 receptor on CD4+CD25+ T cells and correlation with the PD‐1.3A genotype in patients with systemic lupus erythematosus
title_fullStr Lower expression levels of the programmed death 1 receptor on CD4+CD25+ T cells and correlation with the PD‐1.3A genotype in patients with systemic lupus erythematosus
title_full_unstemmed Lower expression levels of the programmed death 1 receptor on CD4+CD25+ T cells and correlation with the PD‐1.3A genotype in patients with systemic lupus erythematosus
title_sort lower expression levels of the programmed death 1 receptor on cd4+cd25+ t cells and correlation with the pd‐1.3a genotype in patients with systemic lupus erythematosus
publisher Wiley
publishDate 2010
url http://dx.doi.org/10.1002/art.27417
https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fart.27417
https://onlinelibrary.wiley.com/doi/pdf/10.1002/art.27417
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op_source Arthritis & Rheumatism
volume 62, issue 6, page 1702-1711
ISSN 0004-3591 1529-0131
op_rights http://onlinelibrary.wiley.com/termsAndConditions#vor
op_doi https://doi.org/10.1002/art.27417
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