Abstract
Background
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 autoimmunity. 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 age.
Objectives
In 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.
Methods
We have assessed aspects of the aged immune phenotype by immunostaining and flow cytometry 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.
Results
We 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.
Conclusion
Accelerated immune ageing is an early feature of RA and biological ageing processes represent novel targets to modulate disease progression.
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 autoimmunity. 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 age.
Objectives
In 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.
Methods
We have assessed aspects of the aged immune phenotype by immunostaining and flow cytometry 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.
Results
We 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.
Conclusion
Accelerated immune ageing is an early feature of RA and biological ageing processes represent novel targets to modulate disease progression.
| Original language | English |
|---|---|
| Pages (from-to) | 1152-1152 |
| Journal | Annals of the Rheumatic Diseases |
| Volume | 81 |
| Issue number | Supplement 1 |
| Early online date | 23 May 2022 |
| DOIs | |
| Publication status | Published - Jun 2022 |
| Event | EULAR European Congress of Rheumatology 2022 - Copenhagen, Denmark Duration: 1 Jun 2022 → 4 Jun 2022 |
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