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
2010 (English)In: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 62, no 6, 1702-1711 p.Article in journal (Refereed) Published
OBJECTIVE.: A genetic polymorphism, PD1.3A, in the PDCD1 gene encoding the co-inhibitory immunoreceptor PD-1, has been associated with SLE. The aim of the study was to assess PD-1 receptor expression in SLE patients, relatives and controls and correlate with PD-1.3A. METHODS.: Icelandic and Swedish SLE patients, relatives and controls were studied. PBMCs were stimulated with alphaCD3/CD28 and PD-1 expression analyzed by flow cytometry. PD-1.3A/G genotyping was performed by PCR-RFLP. RESULTS: I. PD-1 expression on PBMCs was induced after stimulation, by 2.1-fold in SLE patients, 3.1-fold in relatives and 5.1-fold in controls.II. The frequency of PD-1+ cells was significantly lower in SLE patients compared to relatives and controls. PD-1 expression on PD-1+ cells was significantly lower in SLE patients and relatives.III. PD-1 expression on CD4+CD25+ T cells was significantly lower in SLE patients and relatives.IV. PD-1 expression was significantly higher on CD25(high) compared to CD25(intermediate) and (low) cells.V. PD-1 expression on CD25(high) and CD25(intermediate) cells was significantly lower in SLE patients compared to controls.VI. PD-1 was expressed on both FoxP3- and FoxP3+ cells.VII. Lower PD-1 expression was significantly correlated with the PD-1.3A/G genotype. CONCLUSION.: The study demonstrates significantly lower PD-1 receptor expression in SLE patients and relatives and a significant correlation of lower PD-1 expression with the PD-1.3A allele. We conclude that PD-1.3A may be contributory to abnormalities in PD-1 receptor expression on CD4+CD25+ T-cells in SLE, providing support for an important role for the PD-1 pathway in SLE and possibly other autoimmune diseases.
Place, publisher, year, edition, pages
2010. Vol. 62, no 6, 1702-1711 p.
SLE, PD-1.3A, self-tolerance
Immunology in the medical area
Research subject Immunology
IdentifiersURN: urn:nbn:se:uu:diva-107272DOI: 10.1002/art.27417ISI: 000279432500020PubMedID: 20178125OAI: oai:DiVA.org:uu-107272DiVA: diva2:228501