# Enhanced CD56 Expression and Increased Number of CD56+bright Cells in the Peripheral Blood of Untreated Endometriosis Patients

## TL;DR

Untreated endometriosis patients have more CD56+bright NK cells in their blood, which may help diagnose the condition.

## Contribution

The study identifies elevated peripheral CD56+bright NK cells as a potential diagnostic marker for endometriosis.

## Key findings

- Untreated endometriosis patients show increased CD56+bright NK cells compared to controls.
- NKG2D receptor expression is reduced in untreated patients but normalizes with treatment.
- CD56+bright NK cells may migrate from ectopic tissue and impair cytotoxic function.

## Abstract

NK‐cell dysfunction in endometriosis is suggested to contribute to the survival of ectopic endometrial tissue. However, the underlying causes of this impairment remain unclear. NK cells are divided into: CD56+bright, which produce high amounts of cytokines but have low or no cytotoxic ability, and CD56+dim, which are mainly cytotoxic. CD56+bright NK cells, constitutively present in human endometrium (eNK cells), represent only 0–2% of NK cells in PBMC, where CD56+dim cells dominate.

NK‐cell subpopulations and NKG2D receptor expression in PBMC were analyzed by flow cytometry in two cohorts of untreated and treated endometriosis patients and healthy age‐matched controls.

Elevated numbers of CD56+bright cells were observed in 8 of 21 untreated endometriosis patients compared to controls. These numbers were normalized following surgery and hormonal treatment. The NKG2D receptor expression was reduced in untreated patients compared to controls and treated patients.

The significantly increased proportion of peripheral CD56+bright NK/eNK cells may result from migration of these cells from ectopic endometrial tissue. The downregulation of NKG2D receptor expression in PBMCs may be mediated by immunosuppressive endometriotic exosomes, as previously reported by us. Taken together, our results suggest that: (1) the impaired NK cell cytotoxicity in untreated endometriosis patients may be due both to an influx of CD56+bright/eNK cells and exosome‐induced NKG2D receptor downregulation; and (2) elevated numbers of peripheral CD56+bright NK cells could be considered as a potential diagnostic marker for endometriosis.