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New Analysis of Endometriosis Could Help Diagnosis, Treatment

MIT team illuminates complex disease (February 5)

Endometriosis, the invasive displacement of uterine tissue into surrounding organs, affects at least 10% of women. The disease, which is often misdiagnosed, can cause severe pain and infertility, but very little is known about how it arises.

Researchers at the Massachusetts Institute of Technology have identified a pattern of immune-system signaling molecules that correlates with certain symptoms of endometriosis. They have also identified the underlying cellular activity that produces this signature.

The signature, described in the February 5 issue of Science Translational Medicine, could help scientists develop a patient-stratification system similar to that used for breast cancer patients, whose treatments are tailored to the molecular profile of their tumors, said senior author Dr. Linda Griffith.

In the new study, the researchers analyzed peritoneal fluid from 77 patients who reported a range of symptom severity. For each sample, the team measured 50 proteins, including inflammatory compounds known as cytokines. Cytokines regulate the body’s response to infectious agents but can also cause inflammation in the absence of a pathogen, as they do during endometriosis.

The researchers 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 already been implicated in endometriosis. One of the key regulators of this signature that the researchers identified is c-Jun, a protein that drives inflammation. This molecule has been linked to endometriosis, and a drug that inhibits c-Jun is now in clinical trials to treat the disease.

The researchers also found that many of the molecules that make up the newly identified signature are secreted by macrophages, a type of immune cell that acts as a sentinel — patrolling tissues, digesting foreign material, and presenting this material to other immune cells.

The team is now investigating the triggers for this immune response, which are likely not the same in every patient. Such studies could help lead to new drug targets, as well as a better understanding of a highly complex disease, the researchers say.

Source: MIT; February 5, 2014.

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