AGE AND GENDER EFFECTS ON PROGRAMMED CELL DEATH-1 EXPRESSION IN HEALTHY DONORS

Background: Giant cell arteritis (GCA) is the most frequent form of vasculitis affecting the large sized vessels. GCA occurs more frequently in females and exclusively in individuals > 50 years of age but it is unclear how gender and age relate to GCA pathogenesis. In balancing the immune response and preventing immune dysfunction, immune checkpoints are crucial. Recently, the co-inhibitory checkpoint molecule programmed cell death-1 (PD-1) and its ligand PD-L1 were found to be aberrantly expressed in GCA (1). However, data on age and gender related effects on immune checkpoint expression is limited. Objectives: To further investigate the contribution of immune checkpoints in GCA pathogenesis and how this relates to ageing and gender differences, we first studied PD-1 expression as a function of age and gender in healthy males and females. Methods: Whole blood cells of 13 young healthy donors (mean age 25.5 years, female/male ratio 7:6) and 20 elderly healthy donors (mean age 72.7 years, female/male ratio 11:9) were stained for CD3, CD4, CD45RA, CD25 and PD-1 with monoclonal antibodies and expression was measured with flow cytometry. Results: Percentages of PD-1+ cells within CD4+ T cells, memory CD4+ T cells and the subset of non-suppressive regulatory T cells (Tregs, defined as CD4+CD45RA-CD25int) were decreased in elderly post-menopausal females compared to elderly males ( Figure 1A-C ; p<0.05). Furthermore, the frequency of PD-1+ cells within non-suppressive Tregs was also decreased in post-menopausal females compared to young females ( Figure 1C ; p<0.05). Conclusion: PD-1 expression is decreased in (subsets of) CD4+ T cells of post-menopausal females when compared to younger females and elderly males. These findings suggest that post-menopausal status in females can influence PD-1 expression. Further studies on the relation between hormonal changes and immune checkpoint expression may contribute to understanding why elderly females are predisposed to develop GCA. REFERENCE: [1] Zhang H, Watanabe R, Berry GJ, Vaglio A, Liao YJ, Warrington KJ, et al. Immunoinhibitory checkpoint deficiency in medium and large vessel vasculitis. Proc Natl Acad Sci.2017Feb7;114(6):E970–9. Figure 1 Expression of PD1 on (subsets of) CD4+ T cells. Graphs represent percentages of PD-1-expressing total CD4+ T cells (A) and memory CD4+ T cells (B) in elderly post-menopausal females and elderly males, and the percentages of PD-1-expressing non-suppressive Tregs (C) in young females, elderly females, young males and elderly males. Horizontal bars reflect median percentages. Statistical analyses of differences between young and elderly females and elderly females and elderly males were performed using Mann-Whitney U tests. P values are indicated in the graphs. Disclosure of Interests: Rosanne Reitsema: None declared, Rebeca Hid Cadena: None declared, Sander Nijhof: None declared, Wayel Abdulahad: None declared, Minke G. Huitema: None declared, Annemieke Boots Grant/research support from: grant from MSD in 2010-2015, Consultant for: I was a consultant for Grunenthal Germany 2016-2017, Employee of: I was an employee of Organon, Shering-Plough and MSD from 1991-2011, Elisabeth Brouwer Speakers bureau: Dr. Brouwer as an employee of the UMCG received speaker fees and consulting fees from Roche which were paid to the UMCG, Peter Heeringa: None declared DOI: 10.1136/annrheumdis-2019-eular.4823Citation: Ann Rheum Dis, volume 78, supplement 2, year 2019, page A1482Session: Adaptive immunity (T cells and B cells) in rheumatic diseases (Scientific Abstracts)