Identification of a circulating immunological signature as a liquid biopsy approach for the diagnosis of endometriosis

Why this matters to patients and families

Endometriosis affects an estimated 190 million women worldwide, often causing years of pain, heavy periods, and fertility problems before it is correctly diagnosed. Today, doctors usually rely on imaging and sometimes surgery to confirm the disease, which means many women wait 8–10 years for answers. This study explores whether a simple blood test that reads the state of the immune system could offer a faster, less invasive way to spot endometriosis.

A hidden disease that is hard to confirm

Endometriosis occurs when tissue similar to the uterine lining grows in places where it does not belong, such as the ovaries or deep in the pelvis. This misplaced tissue reacts to hormones and triggers chronic inflammation, leading to pelvic pain, painful periods, pain during sex, digestive discomfort, and infertility. Because these symptoms can mimic other conditions, and current tools like ultrasound or MRI do not always detect early or small lesions, many women are left in diagnostic limbo. Existing blood markers, such as CA-125, have proven unreliable, and even promising new tools like microRNA tests can be technically demanding and hard to standardize for everyday clinic use.

Taking a snapshot of the immune system

The researchers asked whether the immune system itself could provide a clearer signal of endometriosis. They recruited 78 women with surgically confirmed endometriosis and 48 women undergoing surgery for contraception, who served as controls. Before surgery, they collected blood and carefully processed the plasma, the liquid portion that carries many signaling proteins. Using bead-based assays, they measured a wide panel of small immune messengers called cytokines and molecules known as soluble immune checkpoints, which help control how strongly immune cells respond. They then applied statistical modeling to see whether patterns across these many factors could distinguish patients from healthy controls.

A distinct immune fingerprint in the blood

Women with endometriosis showed a clear and consistent shift in several immune markers compared with controls. One inflammatory molecule, TNF, was higher, while others involved in guiding immune cells, such as TGF-β1, IP-10, MCP-1, and IL-8, were lower in the bloodstream. Most of the soluble immune checkpoints they examined were also reduced in patients. Together, these changes suggested that endometriosis does not just affect the pelvis; it leaves a recognizable imprint on the whole immune system. When the team combined eight of these altered factors into a single score using logistic regression, the resulting "immune signature" correctly distinguished women with endometriosis from controls with high accuracy, reaching an area under the curve of 0.888, with about 92% sensitivity and 73% specificity.

Boiling it down to a practical test

To make the approach more realistic for routine care, the scientists looked for a simpler set of measurements that would still perform well. They built a second model that mixed just four blood markers (sCD25, sPD-L1, sLAG-3, and IP-10) with two pieces of basic information every clinician already has: age and body mass index. This minimal signature still detected endometriosis with strong performance (area under the curve 0.824, about 92% sensitivity and 60% specificity). Importantly, the score worked consistently across many subgroups: younger and older women, higher and lower BMI, different types of endometriosis, various cyst sizes, fertility status, and the presence or absence of other medical conditions or hormone treatments.

What this could mean in everyday care

For a layperson, the key message is that endometriosis seems to leave a stable “fingerprint” in the blood, based on how the immune system is behaving. By reading this immune pattern through a blood test and simple clinical details, doctors may one day identify women very likely to have endometriosis without immediately resorting to invasive procedures. While the study is still early and based on a single group of patients, and larger, independent trials are needed to confirm the results, it lays the groundwork for a liquid biopsy that could shorten the long diagnostic journey many women face. If validated, such a test could help guide earlier referral, more timely treatment, and better quality of life for those living with this often overlooked disease.

Citation: Hernández, A., Fernández-Medina, O., Araiz, P.A. et al. Identification of a circulating immunological signature as a liquid biopsy approach for the diagnosis of endometriosis. Sci Rep 16, 6052 (2026). https://doi.org/10.1038/s41598-026-36464-8

Keywords: endometriosis, liquid biopsy, immune markers, blood test, womens health