OP0308 SENESCENT PROGENITOR CELLS IN THE SKIN OF LUPUS PATIENTS

Background:Systemic lupus erythematosus (SLE) is an autoimmune disease, which is characterized by skin lesions, amongst other symptoms. These lesions (chronic discoid lupus erythematosus (CDLE) and subacute cutaneous lupus erythematosus (SCLE)) feature lymphocytic infiltration close to basal layer of the epidermis (i.e. the location of the epidermal progenitor cells), namely the epidermal dermal junction (EDJ) area. Epidermal progenitor cells maintain the homeostasis of the skin through their proliferation and differentiation into keratinocytes. In fast turnover tissues, like the skin, a population of ‘transient amplifying cells’ (TA cells), additionally facilitates generation of enough daughter cells to maintain skin homeostasis. These cells are located in an upper layer (suprabasal layer) of the epidermis, next to the basal layer. Senescence is an irreversible and locally spreading phenomenon that induces permanent cell cycle arrest.Objectives:To evaluate expression of senescence markers p16 and p21 in the epidermal progenitor and TA niches in patients with SCLE and CDLE. This was compared to a panel of other dermatological conditions with and without infiltration close to EDJ, as disease controls, and to control skin tissue.Methods:Age-matched skin lesions from patients with SCLE (n=12), CDLE (n=8), other conditions with EDJ infiltration (e.g. lichen planus, n=22), and dermatoses without EDJ infiltration (e.g. eczema, n=27), and non-lesion control biopsies (n=3) from SLE patients were employed. p16 and p21 expression in the progenitor niche (basal layer) and TA cell niche (suprabasal layer), and the whole epidermis of skin lesions biopsies were examined by immunohistochemistry.Results:In healthy skin biopsies, 0 ± 0 SEM p16+ cells/mm2 in the progenitor niche and 5 ± 4 SEM p21+ cells/mm2 in TA niche were observed. In skin lesions from patients with CDLE and SCLE, significantly more p16+ cells in the progenitor cell niche (45 ± 14 SEM/mm2) and p21+ cells (182 ± 38 SEM/mm2) in TA niches were detected, compared to control biopsies (p < 0.05), and compared to those dermatoses without EDJ infiltration (p16+ 11 ± 3 SEM/mm2, p21+ 86 ± 28 SEM/mm2, p < 0.05, Figure 1). p16 and p21 expression in CDLE and SCLE lesions did not significantly differ from other dermatoses with EDJ infiltration (p>0.05). Across all dermatoses analyzed, the number of p16+ cells was significantly correlated with the number of p21+ cells, both in the progenitor niche (r=0.45, p<0.0001) and TA niche (r=0.47, p<0.0001). p16+ cells however were more frequently found in the progenitor cell niche, and p21+ cells conversely in the TA cell niche (p<0.0001).Figure 1.Increased p16+ and p21+ cells in the progenitor and TA niches in dermatoses with EDJ infiltration. A. Graphic illustration for the progenitor cell niche (the basal layer), the transient amplifying (TA, the supra-basal layer) cell niche, and the further differentiated area. B-D. Representative staining of p16 (blue) and epidermal growth factor receptor (EGFR, brown, an epithelial cell marker) in dermatoses with (CDLE) and without (PMLE) epidermal-dermal junction (EDJ) infiltration groups. Black arrowheads point to p16+ progenitor epidermal cells. E-G. Representative staining of p21 (blue) and EGFR (brown) in dermatoses with (CDLE) and without (PMLE) EDJ infiltration groups. Hollow arrowheads point to p21+ TA epidermal cells. The dashed line indicates the EDJ. CDLE: chronic discoid lupus erythematosus, PMLE: polymorphous light eruption.Conclusion:In CDLE and SCLE, cutaneous manifestations of SLE, more progenitor and TA cells expressing markers of senescence were detected. This was in common with other dermatological conditions where lymphocytic infiltration is in close proximity to the progenitor and TA cell niche, namely in the EDJ. Increased senescence might infer the collapse of homeostasis in target (local) epidermis, which may influence tissue repair in the lesion. Elimination of senescent cells may therefore represent a viable therapeutic option to encourage timely and complete wound healing, in skin lesions of CDLE and SCLE patients.Acknowledgements:This research was funded by a China Scholarship Council grant (201606220074), Dutch Arthritis Foundation Translational Research Grant (T015-052) and a Dutch Arthritis Foundation Long Term Project Grant (LLP-29).Disclosure of Interests:None declared.

AB1221 POPULATION WIDE STUDY OF MORTALITY IN ANCA-ASSOCIATED VASCULITIS IN WESTERN AUSTRALIA FROM 2000 TO 2014

Background:Survival in ANCA-associated vasculitis (AAV) has improved substantially in the last fifty years, but Australian data and studies with a control population are scarce.Objectives:The aim of this study was to compare the all-cause mortality rate between patients with AAV and matched controls in Western Australia.Methods:A retrospective population-based cohort study conducted using the Western Australia Health Data Linkage System (WADLS) for patients with a diagnostic code for AAV (International Classification of Diseases (ICD)-10-AM M30.1, M31.3 and M31.7). We included 240 patients with AAV (mean age 57.37 ± 16.69, 48.8% males) who had a hospital admission or emergency department visit between 1 January 2000 and 31 December 2014 and 4406 controls matched for age and sex. Death details were obtained from the WA Death registry. Mortality rates per 1000 person-years (MR) for AAV patients and controls were compared by mortality rate ratios (MRRs) with 95% CI. Kaplan Meijer survival estimates were analyzed by log-rank test.Results:During a mean follow-up of 6.58 years (3.37, 11.25) 83 incident AAV patients (34.6%) died, giving a mortality rate of 48.13 per 1000 person-years (95% CI 38.33, 59.66). This was 82% higher overall than in controls (MRR 1.82, 95% CI 1.46, 2.26, P < 0.0001), while the MRR for males with AAV was 2.28 (95% CI 1.46, 2.26; P < 0.0001) and for females 1.43 (95% CI 1.01, 2.02; P = 0.0267). Survival estimates at one (90.5%) and five years (75%) were significantly lower in AAV patients than controls.Conclusion:Over the last fifteen years, the mortality risk for AAV patients remains significantly increased compared with matched controls and more so for male than female AAV patients. Together with the reduced one- and five-year survival rate, this indicates the need for further improvements in initial disease management in order to reduce the risk of death in AAV.TableMortality rates (MR) per 100 patient years and Mortality rate ratio (MRR) with 95% CI in patients with AAV and controlsAAVControlDeathsPersonyearsMR(95% CI)DeathsPersonyearsMR(95% CI)MRR(95% CI)All83172448.1(38.3, 59.6)12194606926.4(25.0, 27.9)1.82 (1.46, 2.26)Male4978962.1(45.9 82.0)6902529528.2(25.2, 29.3)2.28 (1.72, 3.02)Female3493536.3(25.1, 50.7)5292077325.4 (23.3, 27.7)1.43 (1.01, 2.02)Figure.Kaplan Meyer Survival curves for AAV patients and controlsAcknowledgments:The authors thank the Data Custodians of the Hospital Morbidity Data Collection (HMDC), Emergency Department Data Collection (EDDC), the State Registry of Births, Deaths and Marriages, the WA Electoral Commission, and the staff at Data Linkage Branch at the Western Australian Department of Health for their assistance in provision of data. This work was supported by an unrestricted grant from the Arthritis Foundation of Western Australia. Author WDR received a PhD Scholarship in Memory of John Donald Stewart from the Arthritis Foundation of Western AustraliaDisclosure of Interests:Wade Taylor: None declared, warren raymond: None declared, Helen Keen Speakers bureau: Pfizer Austrlaia, Abbvie Australia, Charles Inderjeeth Consultant of: Linear Research Perth, David Preen: None declared, Johannes (“Hans”) Nossent Speakers bureau: Janssen

Evaluation of Tai Chi Program Effectiveness for People with Arthritis in the Community: A Randomized Controlled Trial

Objective:Evaluate effectiveness of the Arthritis Foundation Tai Chi Program for community participants with arthritis.Methods:343 individuals were randomized to either the intervention or wait-list control group. Performance and self-reported outcome (SRO) measures were assessed at baseline and eight weeks. At one year, SROs only were assessed. Adjusted means were determined using regression models adjusting for covariates, and effect sizes (ES) were calculated.Results:Average participant age was 66 years, 87% were female, and 87% were Caucasian. Among 284 (83%) participants who returned at eight weeks, balance by reach (ES = 0.30) and helplessness, sleep, and role participation satisfaction (ES = 0.24–0.54) improved significantly; pain, fatigue, and stiffness improvement (ES = 0.15–0.23) approached significance. No change was noted in mobility, lower extremity strength, or single-leg stance balance. At one year, improvements in pain, fatigue, stiffness, helplessness, and role participation satisfaction at eight weeks were maintained; 30% continued tai chi practice.Conclusion:Moderate effectiveness of the Arthritis Foundation Tai Chi Program was confirmed.