Vasculitis & polymyalgia rheumatica
A coding single nucleotide polymorphism in the interleukin-6 receptor enhances IL-6 signalling in CD4 T cells and predicts treatment response to tocilizumab in giant cell arteritis
Authors' conclusion
The rs2228145 variant is associated with decreased treatment response to tocilizumab and worse outcomes in GCA by enhancing CD4 T cell response to IL-6.
Study context
- Population
- Patients with giant cell arteritis (GCA) treated with tocilizumab; Peripheral blood mononuclear cells (PBMCs) from patients and controlsderivation 58
- Participants
- 100 patients
- Comparison
- rs2228145 homozygous vs no variant
- Outcome
- Tocilizumab treatment response by rs2228145 genotype
Methodological details2 independent cohorts (derivation and validation), flow cytometry
- 2 independent cohorts (derivation and validation)
- Flow cytometry
Main finding
As reported in the abstract
Tocilizumab response rate, derivation cohort
P = 0.003
Further findings
Tocilizumab response rate, validation cohort
P = 0.04
Mechanistic findings in CD4 T cells
- IL-17-producing CD4 T cells increased in gene dose-dependent response to IL-6
- P < 0.01
- pSTAT3 after IL-6 stimulation significantly increased in gene dose-dependent manner in GCA CD4 T cells, not in controls
- GCA CD4 T cells had significantly higher membrane gp130 than healthy controls; IL-6 response correlated with gp130
Parts of this Brief are withheld: the automatic checks could not confirm them against the abstract.
Original publication
A coding single nucleotide polymorphism in the interleukin-6 receptor enhances IL-6 signalling in CD4 T cells and predicts treatment response to tocilizumab in giant cell arteritis. Ann Rheum Dis. Published 24 February 2025. doi:10.
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