RMD open · 2026
PD1+ TIGIT+ CD4+ T cells predict response to anti-TNF in rheumatoid arthritis and spondyloarthritis.
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Bitoun Samuel, Roulleaux-Dugage Matthieu, Naigeon Marie, de Oliveira Caroline, Berthot Caroline, Mariette Xavier, Nocturne Gaetane, Chaput Nathalie
Аннотация
BACKGROUND: Programmed cell death protein 1 (PD-1) and T cell immunoreceptor with Ig and ITIM domains (TIGIT) are immune checkpoints expressed on T cells. Despite recent development of PD-1 agonists in rheumatoid arthritis (RA), little is known about PD-1 and TIGIT coexpression in RA and other immune-mediated inflammatory diseases (IMIDs). This study quantified PD-1 and TIGIT expression in CD4 and CD8 T cells in patients with IMID and examined associations with disease characteristics and anti-tumour necrosis factor (TNF) response.
METHODS: Biologics-naïve patients with RA and spondyloarthritis (AS) were followed prospectively to assess anti-TNF response at 12 months. Sjögren's disease (SjD) patients and healthy volunteers (HV) were also included at baseline. PD-1 and TIGIT expression on CD4 and CD8 T cells was analysed by flow cytometry at baseline and after 3 months of anti-TNF treatment. Plasma cytokines were quantified using the Meso Scale Discovery assay.
RESULTS: 67 patients were included. Median CD8+PD-1+TIGIT+ levels were higher in RA (24%) and SjD (23.2%) than in HV (18.8%) and AS (16.2%). CD4+PD-1+TIGIT+ were positively correlated with circulating immunoglobulin G (r=0.698, p<0.001), interferon gamma (r=0.635, p=0.017) and IP-10 (r=0.612 p=0.005) levels in patients with SjD. Baseline CD4+PD-1+TIGIT+ levels were higher in future anti-TNF responders (9.9%) compared with non-responders (6.1%, p=0.003). Both CD4+PD-1+TIGIT+ and CD8+PD-1+TIGIT+ cells increased after 3 months of anti-TNF treatment in RA and AS.
CONCLUSION: CD8+PD-1+TIGIT+ T-cell expression is elevated in SjD and RA compared with HV and AS. CD4+PD-1+TIGIT+ levels are higher in future anti-TNF responders compared with non-responders and rise after treatment in patients with RA and AS. Further studies should clarify the functional role of CD4+PD-1+TIGIT+ cells in IMIDs.
METHODS: Biologics-naïve patients with RA and spondyloarthritis (AS) were followed prospectively to assess anti-TNF response at 12 months. Sjögren's disease (SjD) patients and healthy volunteers (HV) were also included at baseline. PD-1 and TIGIT expression on CD4 and CD8 T cells was analysed by flow cytometry at baseline and after 3 months of anti-TNF treatment. Plasma cytokines were quantified using the Meso Scale Discovery assay.
RESULTS: 67 patients were included. Median CD8+PD-1+TIGIT+ levels were higher in RA (24%) and SjD (23.2%) than in HV (18.8%) and AS (16.2%). CD4+PD-1+TIGIT+ were positively correlated with circulating immunoglobulin G (r=0.698, p<0.001), interferon gamma (r=0.635, p=0.017) and IP-10 (r=0.612 p=0.005) levels in patients with SjD. Baseline CD4+PD-1+TIGIT+ levels were higher in future anti-TNF responders (9.9%) compared with non-responders (6.1%, p=0.003). Both CD4+PD-1+TIGIT+ and CD8+PD-1+TIGIT+ cells increased after 3 months of anti-TNF treatment in RA and AS.
CONCLUSION: CD8+PD-1+TIGIT+ T-cell expression is elevated in SjD and RA compared with HV and AS. CD4+PD-1+TIGIT+ levels are higher in future anti-TNF responders compared with non-responders and rise after treatment in patients with RA and AS. Further studies should clarify the functional role of CD4+PD-1+TIGIT+ cells in IMIDs.