Molecular Network Analysis Could Help Diagnoses Endometriosis

A neoteric analysis of endometriosis patients could help scientists develop better treatments and more revealing diagnoses for a disease, which is often misdiagnosed, and can cause severe pain and infertility.

A pattern of immune system signaling molecules has been identified that correlates with certain symptoms of endometriosis and the underlying cellular activity that produces this signature has also been identified by measuring inflammatory compounds known as cytokines.

Scientists at the Massachusetts Institute of Technology (Cambridge, MA, USA) analyzed peritoneal fluid from 77 patients who reported a wide range of symptom severity. Leukocyte and erythrocyte contents of the primary aspirate were determined by hemocytometer count and total protein concentration was determined by bicinchoninic acid assay (Thermo Scientific Pierce; Rockford, IL, USA).

Multiplex cytokine immunoassays were performed for 50 peritoneal cytokines, chemokines, and growth factors determinations using group I 27-plex, group II 21-plex, and ICAM-1 and VCAM-1 singleplex immunoassay panels (Bio-Rad Laboratories; Hercules, CA, USA). Macrophage prevalence in peritoneal aspirates was assessed by flow cytometric quantitation of cluster of differentiation CD45+/CD68+ leukocytes. Gene set enrichment and coexpression analysis was also performed to assess enrichment for cytokine production across resting and activate immune cell lineages.

The scientists found a distinctive profile of cytokine activity associated with certain symptoms, specifically ovarian and rectovaginal lesions. This pattern, which included 13 cytokines, was also negatively correlated with patient fertility. Many of the inflammatory compounds that make up the newly discovered signature have previously been implicated in endometriosis. One of the key regulators of this signature that the team identified was c-Jun, a protein that drives inflammation. This molecule has been linked to endometriosis before, and a drug that inhibits c-Jun is now in clinical trials to treat the disease.

Linda Griffith, PhD, a professor of biological and mechanical engineering and the senior author of the study said, “This paper isn't to say we discovered the answer. We're trying to start a conversation with a broad translational science community about this because it is such a terrible disease. We found something really interesting, but it's only the tip of the iceberg, and if other clinicians are interesting in setting up a similar study with their patients, we're happy to talk about collaborating with them.” The study was published on February 5, 2014, in the journal Science Translational Medicine.

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