POS0391 ASSESSING SENESCENT HUMAN LYMPH NODE STROMAL CELLS DURING RHEUMATOID ARTHRITIS DEVELOPMENT
Background: Cellular senescence is a state of proliferation arrest of cells. The persistence and accumulation of senescent cells has been implicated in the pathogenesis of age-related diseases like rheumatoid arthritis (RA). Clinical disease is preceded by loss of immune tolerance and autoimmunity....
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Published in | Annals of the rheumatic diseases Vol. 80; no. Suppl 1; p. 425 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
London
BMJ Publishing Group LTD
01.06.2021
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Subjects | |
Online Access | Get full text |
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Summary: | Background:
Cellular senescence is a state of proliferation arrest of cells. The persistence and accumulation of senescent cells has been implicated in the pathogenesis of age-related diseases like rheumatoid arthritis (RA). Clinical disease is preceded by loss of immune tolerance and autoimmunity. Lymph node stromal cells (LNSC) are important regulators of this tolerance. Therefore, senescent LNSC may affect tolerance and the development of systemic autoimmunity.
Objectives:
To determine the extent of cellular senescence of LNSC during early phases of systemic autoimmunity.
Methods:
We included individuals with arthralgia without any evidence of arthritis who were positive for IgM rheumatoid factor (IgM-RF) and/or anti-citrullinated protein antibodies (ACPA; RA-risk group), early arthritis patients (ACR/EULAR 2010 criteria; disease duration < 1 year) and seronegative healthy controls. All study subjects underwent ultrasound-guided inguinal lymph node biopsy. LNSC were isolated and cultured from freshly collected lymph node needle biopsies and passages 0-9 were used for experiments. Cellular senescence was assessed by measuring cell size, granularity, autofluorescence, senescence-associated gene expression levels, DNA damage and senescence-associated β-galactosidase (SA β-gal) activity.
Results:
Preliminary flow cytometry data shows that the cell size and autofluorescence of LNSC from RA patients (n=11) and RA-risk individuals (n=7) is increased compared with healthy LNSC (n=7), while granularity was specifically increased in LNSC from RA patients (n=9). Initial stainings indicate higher SA β-gal activity and more DNA damage in LNSC from RA-risk (n=3) and RA patients (n=4) compared with healthy controls (n=3). Expression levels of senescence-associated genes such as p21 and p53 were significantly higher in LNSC from RA patients compared with healthy controls (n=6 per group).
Conclusion:
These preliminary findings suggest senescence already in early RA and provide a rationale for investigating the consequence of senescent LNSC on immune cell responses
Disclosure of Interests:
None declared |
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ISSN: | 0003-4967 1468-2060 |
DOI: | 10.1136/annrheumdis-2021-eular.2501 |