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.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Uppsala University, Uppsala, Sweden.
authors.forename: Helga
authors.initials: H
authors.lastname: Kristjansdottir
authors.forename: Kristjan
authors.initials: K
authors.lastname: Steinsson
authors.forename: Iva
authors.initials: I
authors.lastname: Gunnarsson
authors.forename: Gerdur
authors.initials: G
authors.lastname: Gröndal
authors.forename: Kristjan
authors.initials: K
authors.lastname: Erlendsson
authors.forename: Marta E
authors.initials: ME
authors.lastname: Alarcón-Riquelme
mesh_terms: D002478:Cells, Cultured; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D011110:Polymorphism, Genetic; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
chemical_list: D051858:Forkhead Transcription Factors; D011971:Receptors, Immunologic