Use of the population of slamf4+ ccr5+ effector memory cd4+ t cells as a biomarker in rheumatoid arthritis

CD4+ Foxp3- conventional T cells (Tconv) play a key role in the inflammatory process involved in rheumatoid arthritis (RA). It is now becoming increasingly clear that in RA, chronic Tconv stimulation does not induce a sufficient level of exhaustion to inhibit their pathological response. The inventors/’ objectives were to determine whether SLAMF receptors are involved in the establishment of the Tconv pro-inflammatory response and whether these receptors represent a protection against Tconv exhaustion. Thus the inventors immunophenotyped blood T cells from RA patients (n=64) and from healthy donors (HD) (n=14) using a 13-marker flow cytometry panel. The expression of SLAMF receptors was determine among four Tconv subpopulations with different activation status (naive, central memory, effector memory and terminally differentiated effector CD4+ T cells). To assess the inflammatory tropism and functionality of different Tconv subpopulations, CCR5 expression was studied. Only the frequency of SLAMF4+ cells among effector memory T cells (Tem; CCR7-, CD45RA-) was correlated with disease activity. More particularly, the inventors showed that only SLAMF4+ Tem expressing CCR5 were linked to RA activity. The inventors revealed that SLAMF4+ CCR5+ Tem represent a distinct Tconv subpopulation resistant to PD-1 mediated inhibition and strongly linked to RA activity.

Keywords: rheumatoid arthritis (RA), Biomarker, Prognosis, Flow Cytometry, SLAMF4
Patent Application number: International Procedure (PCT) - 14 Nov. 2022 - PCT/EP2022/081802
Inventors:
BITON Jérôme,BOUZIDI Houda Ghozlane,BESSIS Natacha,LACAUD Mégane,BOISSIER Marie-Christophe

Reference:

BIO22284-D1

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Patent filling date: 2022-11-14

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