Science Article:" Probing the pain Katie Burns is helping uncover the role of the immune system in endometriosis—while managing the disease herself"

[Kiristar]

I thought I would share this article since it goes into the recent immunological progress and findings in the development of Endometriosis and discusses potential new clinical trials focusing on the immune system aspect.

https://www.science.org/content/article/driven-pain-endometriosis-scientist-uncovering-clues-its-causes

Findings were
- low number of NK cells
- increased neutrophils that are misshapen
- macrophage involvement (I was not clear how sorry)

I cant help but wonder if the same underlying immune system problem that drives my DIE also facilitates my ME/CFS....

The actual research the article was prompted by:

JCI Insight - Neutrophils initiate proinflammatory immune responses in early endometriosis lesion development

 

[Kiristar]

Immune system targeting treatments under exploration mentioned were:

"-A Chinese company called Hope Medicine last fall reported significant improvements in pain in patients treated during a phase 2 trial of HMI-115, an antibody that locally attacks the prolactin receptor in endometriosis lesions. Prolactin is a hormone that attracts and activates neutrophils, promotes blood vessel growth, and activates nerves in lesions, spurring pain.

-Another antibody, AMY109, made by Chugai Pharmaceutical, attacks interleukin-8, an inflammatory cytokine pumped out by macrophages and neutrophils drawn to the site of misplaced tissue. It shrank lesions and reduced scarring in monkey studies and was shown to be safe and well tolerated in an initial human trial. The company last year launched a larger, phase 2 trial.

-Findings by other researchers not yet in the clinic are pointing to the potential of checkpoint inhibitors, drugs made famous in cancer immunotherapies, in endometriosis—for instance to restore the cell-killing ability of natural killer cells.

- And a team at the University of Edinburgh is preparing to launch a pilot trial of a compound called nibrozetone that targets macrophages, improving their cell-eating ability and nudging them away from their wound-healing, lesion-supporting tendencies."

 

[SNT Gatchaman]

The actual research the article was prompted by

Neutrophils initiate proinflammatory immune responses in early endometriosis lesion development
Taylor R Wilson; Kurt R Peterson; Stephanie A Morris; Damaris Kuhnell; Susan Kasper; Katherine A Burns

Endometriosis is a chronic gynecological disease that affects 1 in 10 reproductive-aged women. Most studies investigate established disease; however, the initiation and early events in endometriotic lesion development remain poorly understood.

Our study used neutrophils from human menstrual effluent from patients with and without endometriosis for immunophenotyping, and it used a mouse model of endometriosis and a mouse endometriosis cell line to determine the role of neutrophils in the initiating events of endometriosis, including attachment and survival of minced endometrial pieces.

In menstrual effluent from women with endometriosis, the ratios of aged and proangiogenic neutrophils increased compared with controls, indicating a potentially permissive proinflammatory microenvironment. In our endometriosis mouse model, knocking down neutrophil recruitment with α-CXCR2 into the peritoneum decreased endometrial tissue adhesion — supported by decreased levels of myeloperoxidase and neutrophil elastase in both developing lesions and peritoneal fluid. Fibrinogen was identified as the preferred substrate for endometrial cell adhesion in an in vitro adhesion assay and in developing lesions in vivo.

Together, aged and proangiogenic neutrophils and their secretions likely promote attachment and formation of endometriotic lesions by releasing neutrophil extracellular traps and upregulating fibrinogen expression as a provisional matrix to establish attachment and survival in the development of endometriosis lesions.

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