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

• 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
• Subjects: Iceland
• Online Access: 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

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.