# IFNγ+ NKT-like cells are associated with increased incidence of atrial fibrillation in elderly women

**Authors:** Kari Anne Sveen, J Gustav Smith, Daniel Engelbertsen, Alexandru Schiopu, Andreas Edsfeldt, Gunnar Engström, Isabel Goncalves, Jan Nilsson, Harry Björkbacka, Eva Bengtsson

PMC · DOI: 10.1093/ehjopen/oeaf063 · 2025-06-05

## TL;DR

High levels of IFNγ+ NKT-like cells in blood are linked to a higher risk of developing atrial fibrillation in elderly women.

## Contribution

Identifies a sex-specific association between IFNγ+ NKT-like cells and atrial fibrillation risk.

## Key findings

- Women with high NKT-like cells had an 1.88-fold increased risk of AF.
- IFNγ+ NKT-like cells were more prevalent in women who developed AF.
- No significant AF risk was observed in men with high NKT-like cells.

## Abstract

T cells are present in atrial tissue from atrial fibrillation (AF) patients. However, prospective studies of T cells and AF development are few. The current aim was to investigate if T-cell subsets are associated with the risk of developing AF.

T-cell subsets, measured by flow cytometry of cryopreserved mononuclear leucocytes isolated from blood at baseline, were analysed for associations of incident AF in 669 subjects from a population-based cohort. Subjects were followed for incidence of AF for 18.6 (11.5–21.7) years during which 145 subjects were diagnosed with AF. Incident AF cases had higher levels of CD3+CD56+ NKT-like cells. No differences in CD3+, CD3+CD4+, CD3+CD8, Th1, Th2, or regulatory T cells between incident AF cases and non-cases were observed. Women had higher levels of NKT-like cells than men. High numbers of NKT-like cells were associated with an increased risk of developing AF in women [HR (95% CI) 1.88 (1.10–3.23) above vs. below median], but not in men or in the total cohort. The majority of NKT-like cells were IFNγ+ after stimulation. High numbers of IFNγ+ NKT-like cells were associated with increased risk for developing AF in women. Median fluorescence intensity of IFNγ for NKT-like cells was higher in cases of incident AF in women, but not in the total cohort or in men.

High levels of IFNγ+ NKT-like cells in blood are associated with increased risk of incident AF in women, supporting a role for T cells in development of AF and emphasizing sex differences in this context.

Graphical Abstract

## Linked entities

- **Proteins:** IFNG (interferon gamma)
- **Diseases:** atrial fibrillation (MONDO:0004981)

## Full-text entities

- **Genes:** CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, NCAM1 (neural cell adhesion molecule 1) [NCBI Gene 4684] {aka CD56, MSK39, NCAM}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}
- **Diseases:** AF (MESH:D001281)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12198755/full.md

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Source: https://tomesphere.com/paper/PMC12198755