Journal
CELLS
Volume 10, Issue 3, Pages -Publisher
MDPI
DOI: 10.3390/cells10030647
Keywords
RA; ACPA; B cells; T cells; synovial tissue
Categories
Funding
- Health Research Board of Ireland [ILP-POR2017-047]
- Centre for Arthritis and Rheumatic Diseases [CARD-2019-01]
- Arthritis Ireland
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Rheumatoid arthritis (RA) is a progressive autoimmune disease affecting 1% of the world population, with anti-citrullinated protein autoantibodies (ACPA) used for diagnosing. ACPA status can be a delineator of RA disease endotypes with unique immunological mechanisms, necessitating a targeted treatment approach for both ACPA-positive and ACPA-negative RA patients.
Rheumatoid arthritis (RA) is a progressive erosive autoimmune disease that affects 1% of the world population. Anti-citrullinated protein autoantibodies (ACPA) are routinely used for the diagnosis of RA, however 20-30% of patients are ACPA negative. ACPA status is a delineator of RA disease endotypes with similar clinical manifestation but potentially different pathophysiology. Profiling of key peripheral blood and synovial tissue immune populations including B cells, T follicular helper (Tfh) cells and CD4 T cell proinflammatory cytokine responses could elucidate the underlying immunological mechanisms involved and inform a treat to target approach for both ACPA-positive and ACPA-negative RA. Detailed high dimensionality flow cytometric analysis with supervised and unsupervised algorithm analysis revealed unique RA patient peripheral blood B cell and Tfh cell profiles. Synovial tissue single cell analysis of B cell subpopulation distribution was similar between ACPA- and ACPA+ RA patients, highlighting a key role for specific B cell subsets in both disease endotypes. Interestingly, synovial tissue single cell analysis of CD4 T cell proinflammatory cytokine production was markedly different between ACPA- and APCA+ RA patients. RNAseq analysis of RA patient synovial tissue highlighted disease endotype specific gene signatures. ACPA status associates with unique immune profile signatures that reinforce the need for a treat to target approach for both endotypes of RA.
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