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- Duggal, N, et al.
(författare)
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INVESTIGATING THE ROLE OF ACCELERATED IMMUNESENESCENCE IN THE PATHOGENESIS OF RHEUMATOID ARTHRITIS
- 2022
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 81, s. 1152-1152
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Advancing age is recognised as a major risk factor for autoimmune inflammatory conditions, such as Rheumatoid Arthritis (RA). Despite strong associations with older age we understand little of the role ageing processes play in disease pathogenesis in RA. The immune system undergoes a dramatic remodelling with age, termed immunesenescence, which contributes towards increased risk of autoimmunity1. Previous research in patients with established RA has shown certain features of immunesenescence, such as thymic atrophy and telomere shortening in T cells, at a younger age2,3.ObjectivesIn this study we aimed to determine if immunesenescence is seen in the very earliest stages of RA and therefore might be a contributor to RA pathogenesis rather than a result of the disease.MethodsWe have assessed aspects of the aged immune phenotype by immunostaining and flow cytometry4 in adults with arthralgia (n=25), undifferentiated arthritis (UA; n=41), confirmed RA of less than 3 months (n=25) and more than 3 months duration (n=78) and compared these to age and sex matched healthy controls (n=38). Nanostring methodology was used to determine gene expression changes associated with the development of RA.ResultsWe observed increased features of T and B cell immunesenescence in DMARD-naïve recently diagnosed RA patients driven by reduced naïve T cells (p<0.01) and B cells (p<0.01), increased senescent (CD28-ve, CD57+ve, KLRG1+ve) T cells (p<0.01), an increased Th17/Treg ratio (p<0.01) and increased frequency of age-associated B cells (p<0.01). With the exception of naïve T cell frequency, which was reduced in UA patients (p<0.05), these changes were not seen in the very early stages of RA, namely patients with arthralgia and UA. These data suggest that immunesenescence only occurs once disease is established. Furthermore, using nanostring we have identified several biological ageing processes (DNA damage, autophagy) associated with this state of immunesenescence in RA.ConclusionAccelerated immune ageing is an early feature of RA and biological ageing processes represent novel targets to modulate disease progression.References[1]Duggal NA, Upton JA, Phillips AC, Sapey E, Lord JM (2013) An age-related numerical and functional deficit in CD19+CD24hiCD38hi B cells is associated with an increase in systemic autoimmunity. Aging Cell 12:873-881.[2]Goronzy, J.J. and Weyand CM (2001). Thymic function and peripheral T-cell homeostasis in rheumatoid arthritis. Trends Immunol. 22(5):251-5.[3]Steer SE, Williams FMK, Kato B, Gardner JP, Norman PJ, Hall MA, Kimra M, Vaughan R, Aviv A, Spector T (2007) Reduced telomere length in rheumatoid arthritis in independent of disease activity and duration. Ann Rheum Dis 66:476-480.[4]Duggal NA, Pollock RD, Lazarus NR, Harridge S, Lord JM (2018). Major features of immunesenescence, including reduced thymic output, are ameliorated by high levels of physical activity in adulthood. Aging Cell 17:e12750Disclosure of InterestsNone declared
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| 2. |
- Sharma-Oates, A, et al.
(författare)
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INCREASED BIOLOGICAL AGE IN MALE PARTICIPANTS OF SWEDISH AND UK RHEUMATOID ARTHRITIS COHORTS IS NOT LINKED TO DISEASE
- 2022
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 81, s. 1177-1177
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Immunesenescence in the adaptive immune system, subsequent to thymic involution, results in compromised immunity and increased susceptibility to autoimmune disease and chronic inflammation. There are reports in the literature that immunesenescence, including thymic atrophy and telomere shortening, is accelerated in patients with rheumatoid arthritis (RA)1. What is unclear is whether RA includes accelerated biological ageing overall in addition to immune ageing which may help to explain the increased risk of age-related diseases in RA2. Recent studies have identified a set of DNA methylated sites across the genome that are highly correlated with chronological age and mortality, termed epigenetic clocks3,4 or DNAm age (DNAma), and can be used to determine an individual’s biological age.ObjectivesThe aim of our study is to determine if the biological epigenetic clocks of RA patients are accelerated.MethodsWe evaluated the Horvath3 and Hannum4 epigenetic clocks of control and RA patients using published DNAm data sets, accessions GSE42861 (EIRA, Swedish cohort of 342 RA patients and 328 non-RA controls) and E-MTAB-6988 (77 RA discordant monozygotic twins).ResultsWe did not detect significant differences between DNAma of RA and non-RA twins. Similarly, there were no significant differences between the DNAma of RA patients and controls from the Swedish EIRA cohort. However, we detected a significant acceleration in DNAma of male discordant twins, both RA and non-RA, by 5.4 years (p=3.29e-5) and 2.8 years (p=0.04) using the Hannum and Horvath clocks, respectively. Male participants, both control and RA patients, from the EIRA cohort also exhibited an accelerated DNAma, by 1.5 years (p=7.55e-5) using the Hannum clock but using the Horvath clock a significant DNAma acceleration, by 1.4 years (p=0.002) was detected in male RA patients from the EIRA cohort.ConclusionOverall, we detected a significant biological age acceleration in male participants from both RA and control groups and only found a significant difference between DNAma of Non-RA controls and RA patients for one of the epigenetic clocks. Further analysis using additional cohort data and biological clock algorithms is needed to confirm our findings.References[1]Goronzy, J.J. and Weyand CM (2001). Thymic function and peripheral T-cell homeostasis in rheumatoid arthritis. Trends Immunol. 22(5):251-5.[2]Meune C, et al. (2009) Trends in cardiovascular mortality in patients with rheumatoid arthritis over 50 years: a systematic review and meta-analysis of cohort studies. Rheumatol 48:1309-1313.[3]Horvath S (2013) DNA methylation age of human tissues and cell types. Genome Biol 14:R115.[4]Hannum G, et al (2013) Genome-wide Methylation Profiles Reveal Quantitative Views of Human Aging Rates. Mol Cell 49:359-367.AcknowledgementsThe study was funded by FOREUMDisclosure of InterestsNone declared
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| 5. |
- Kazakos, K., et al.
(författare)
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A real-time IVR platform for community radio
- 2016
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Ingår i: Conference on Human Factors in Computing Systems - Proceedings. - New York, NY, USA : ACM.
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Konferensbidrag (refereegranskat)abstract
- Interactive Voice Response (IVR) platforms have been widely deployed in resource-limited settings. These systems tend to afford asynchronous push interactions, and within the context of health, provide medication reminders, descriptions of symptoms and tips on self-management. Here, we present the development of an IVR system for resource-limited settings that enables real-time, synchronous interaction. Inspired by community radio, and calls for health systems that are truly local, we developed ’Sehat ki Vaani’. Sehat ki Vaani is a real-time IVR platform that enables hosting and participation in radio chat shows on community-led topics. We deployed Sehat ki Vaani with two communities in North India on topics related to the management of Type 2 diabetes and maternal health. Our deployments highlight the potential for synchronous IVR systems to offer community connection and localised sharing of experience, while also highlighting the complexity of producing, hosting and participating in radio shows in real time through IVR. We discuss the relative strengths and weaknesses of synchronous IVR systems, and highlight lessons learnt for interaction design in this area.
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