Unbiased immune profiling reveals a natural killer cell-peripheral nerve axis in fibromyalgia, 2021, Vivek et al

[Andy]

The pathophysiology of fibromyalgia syndrome (FMS) remains elusive, leading to a lack of objective diagnostic criteria and targeted treatment.

We globally evaluated immune system changes in FMS by conducting multiparametric flow cytometry analyses of peripheral blood mononuclear cells and identified a natural killer (NK) cell decrease in patients with FMS. Circulating NK cells in FMS were exhausted yet activated, evidenced by lower surface expression of CD16, CD96, and CD226 and more CD107a and TIGIT. These NK cells were hyperresponsive, with increased CCL4 production and expression of CD107a when co-cultured with human leukocyte antigen null target cells. Genetic and transcriptomic pathway analyses identified significant enrichment of cell activation pathways in FMS driven by NK cells. Skin biopsies showed increased expression of NK activation ligand, unique long 16–binding protein, on subepidermal nerves of patients FMS and the presence of NK cells near peripheral nerves.

Collectively, our results suggest that chronic activation and redistribution of circulating NK cells to the peripheral nerves contribute to the immunopathology associated with FMS.

Paywall, https://journals.lww.com/pain/Abstr...profiling_reveals_a_natural_killer.97873.aspx

 

[Ravn]

The pathophysiology of fibromyalgia syndrome (FMS) remains elusive, leading to a lack of objective diagnostic criteria and targeted treatment.

We globally evaluated immune system changes in FMS by conducting multiparametric flow cytometry analyses of peripheral blood mononuclear cells and identified a natural killer (NK) cell decrease in patients with FMS. Circulating NK cells in FMS were exhausted yet activated, evidenced by lower surface expression of CD16, CD96, and CD226 and more CD107a and TIGIT. These NK cells were hyperresponsive, with increased CCL4 production and expression of CD107a when co-cultured with human leukocyte antigen null target cells. Genetic and transcriptomic pathway analyses identified significant enrichment of cell activation pathways in FMS driven by NK cells. Skin biopsies showed increased expression of NK activation ligand, unique long 16–binding protein, on subepidermal nerves of patients FMS and the presence of NK cells near peripheral nerves.

Collectively, our results suggest that chronic activation and redistribution of circulating NK cells to the peripheral nerves contribute to the immunopathology associated with FMS.

Paywall, https://journals.lww.com/pain/Abstr...profiling_reveals_a_natural_killer.97873.aspx

This study is now open access (via pdf download):
https://journals.lww.com/pain/Abstr...profiling_reveals_a_natural_killer.97873.aspx

Cort's write-up:
https://www.healthrising.org/blog/2022/04/29/natural-killer-small-nerve-fibers-fibromyalgia/

 

[voner]

@Ravn,

thanks for posting those lniks. That is an impressive paper.

 

[voner]

here is one of their conclusions…

we propose a new heuristic model of the immunopathology of FMS (Fig. 7). According to our model, in FMS, peripheral nerves chronically express NK activation ligand(s), leading to the extravasation and peripheral recruitment of circulating NK cells. This extravasation leads to a reduced number of circulating NK cells in the blood.

 

[rvallee]

For the biologically uninitiated (like me), wiki:

Extravasation is the leakage of a fluid out of its container into the surrounding area, especially blood or blood cells from vessels. In the case of inflammation, it refers to the movement of white blood cells from the capillaries to the tissues surrounding them.​