Expression of Toll-like Receptors on Lymphocyte Subpopulations and Their Soluble Forms in Serum and Urine of Women with Endometriosis
Abstract
1. Introduction
2. Materials and Methods
2.1. Patient Characteristics
- Confirmed diagnosis of endometriosis by histopathological and clinical evaluation;
- Age ≥ 18 years;
- No immunosuppressive treatment within the past 12 months;
- No use of hormonal contraception (including intrauterine systems);
- Provision of written informed consent to participate in the study.
- Presence of uterine fibroids or adenomyosis;
- Active bacterial, viral, or fungal infections;
- Diabetes mellitus or other metabolic/endocrine disorders;
- Chronic wounds, severe allergic diseases, or significant systemic illnesses affecting the kidneys, gastrointestinal tract, heart, or lungs, as well as adherence to strict elimination diets;
- History of hematopoietic stem cell or organ transplantation;
- Active malignancy or autoimmune disorders;
- Pregnancy or breastfeeding;
- Use of immunosuppressive medications or participation in other clinical trials;
- Presence of CNS metastatic disease or diagnosed psychiatric disorders.
- Peritoneal endometriosis (PE);
- Ovarian endometriosis (OE);
- Deeply infiltrating endometriosis (DIE);
- Cesarean section scar endometriosis (CC).
2.2. Immunophenotyping
2.3. Determination of the Concentration of Soluble Forms of TLRs in the Tested Material
2.4. Statistical Analyses
3. Results
3.1. Comparison of Immunological and Biochemical Parameters Between Patients with Endometriosis and Healthy Women
3.2. Comparison of Immunological and Biochemical Parameters in Patients with Different Forms of Endometriosis: Peritoneal, Ovarian, Deeply Infiltrating, and Cesarean Section Scar
3.3. Diagnostic Value of TLR Expression and Their Soluble Forms in Endometriosis—ROC Curve Analysis
4. Discussion
- Peritoneal endometriosis (PE): Involves superficial lesions on the serosa of the abdominal and pelvic cavities. These lesions are typically multifocal, small, and vary in color (red, black, or white), often accompanied by local fibrosis and inflammatory infiltration. PE is most frequently diagnosed during laparoscopy and commonly manifests as chronic pelvic pain.
- Ovarian endometriosis (OE): Characterized by the presence of endometriotic ovarian cysts (so-called “chocolate cysts”) filled with thick, hemorrhagic content. These lesions contribute to structural damage to ovarian tissue, reduced ovarian reserve, and decreased fertility.
- Deeply infiltrating endometriosis (DIE): The most severe form, defined by lesions penetrating more than 5 mm into extraperitoneal tissues. DIE may affect the sacrotuberous ligaments, rectovaginal septum, bladder wall, intestines, and, rarely, the diaphragm or lungs. This form is typically associated with severe pelvic pain, dyspareunia, gastrointestinal symptoms, and infertility.
- Cesarean section scar endometriosis (CC): A less frequent form, occurring in the subcutaneous tissue or muscle layers of the anterior abdominal wall, usually in the region of surgical scars following cesarean delivery. It typically presents as cyclic pain localized to the scar area that intensifies during menstruation.
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
BAS | basophils |
CC | cesarean section scar endometriosis |
CD | cluster of differentiation |
CD3 | T lymphocytes |
CD4 | T helper lymphocytes |
CD8 | cytotoxic T lymphocytes |
CD19 | B lymphocytes |
CD45 | total leukocytes |
CRP | C-reactive protein |
DAMPs | danger-associated molecular patterns |
DIE | deeply infiltrating endometriosis |
EM | endometriosis |
EOS | eosinophils |
HGB | hemoglobin |
HV | healthy volunteers |
IgA | immunoglobulin A |
IgG | immunoglobulin G |
IgM | immunoglobulin M |
IL-6 | interleukin-6 |
IL-8 | interleukin-8 |
LPS | lipopolysaccharides |
LYM | lymphocytes |
MON | monocytes |
MRI | magnetic resonance imaging |
MyD88 | myeloid differentiation primary response 88 |
NEU | neutrophils |
NF-κB | nuclear factor kappa-light-chain-enhancer of activated B cells |
NK | natural killer cells |
OE | ovarian endometriosis |
PAMPs | pathogen-associated molecular patterns |
PE | peritoneal endometriosis |
PLT | platelets |
PRRs | pattern recognition receptors |
ROC | receiver operating characteristic |
RBC | red blood cells |
sTLR | soluble Toll-like receptor |
STAT | signal transducer and activator of transcription |
TLR | Toll-like receptor |
TLRs | Toll-like receptors |
TNF-α | tumor necrosis factor alpha |
TRIF | TIR-domain-containing adapter-inducing interferon-β |
WBC | white blood cells |
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Parameters | EM (n = 50) | HV (n = 24) | p-Value | |||
---|---|---|---|---|---|---|
Median | Q1–Q3 | Median | Q1–Q3 | |||
Hematological, inflammatory, and immunoglobulin parameters | RBC [M/µL] | 4.52 | 4.10–4.71 | 4.53 | 4.18–4.64 | 0.850 |
WBC [K/µL] | 6.10 | 5.04–7.73 | 6.01 | 5.71–7.15 | 0.718 | |
LYM [K/µL] | 1.79 | 1.43–2.29 | 1.68 | 1.39–1.83 | 0.180 | |
MON [K/µL] | 0.52 | 0.42–0.60 | 0.52 | 0.49–0.63 | 0.626 | |
BAS [K/µL] | 0.03 | 0.02–0.06 | 0.04 | 0.03–0.05 | 0.367 | |
EOS [K/µL] | 0.02 | 0.01–0.07 | 0.16 | 0.11–0.23 | <0.0001 * | |
NEU [K/µL] | 4.43 | 3.68–5.43 | 3.26 | 2.38–4.16 | <0.0001 * | |
HGB [g/dL] | 13.15 | 12.20–13.85 | 12.90 | 12.50–13.80 | 0.895 | |
PLT [K/µL] | 256.55 | 206.75–335.00 | 270.5 | 249.00–302.50 | 0.562 | |
CRP [mg/L] | 5.61 | 3.51–6.60 | 2.76 | 1.54–3.32 | <0.0001 * | |
IgG [g/L] | 7.84 | 7.20–8.75 | 11.81 | 8.53–13.55 | <0,0001 * | |
IgM [g/L] | 4.28 | 3.71–5.10 | 1.59 | 1.38–2.33 | <0,0001 * | |
IgA [g/L] | 4.70 | 3.76–5.94 | 1.95 | 1.68–2.36 | <0,0001 * | |
Immunophenotypic characterization of lymphocyte subpopulations | CD45+ [%] | 87.86 | 81.86–91.80 | 96.28 | 92.83–98.05 | <0.0001 * |
CD3+ [%] | 66.02 | 59.95–74.20 | 72.34 | 70.70–76.54 | 0.0012 * | |
CD4+ [%] | 41.84 | 27.20–51.37 | 47.49 | 44.77–49.84 | 0.0144 * | |
CD8+ [%] | 20.51 | 17.31–28.39 | 27.23 | 25.88–28.52 | 0.0021 * | |
CD19+ [%] | 11.27 | 10.17–14.35 | 12.70 | 11.82–13.69 | 0.032 * | |
NK cells [%] | 9.24 | 4.26–17.72 | 7.90 | 7.67–10.89 | 0.042 * |
Group | n | Median Age (Years) | Age Range (Years) |
---|---|---|---|
Peritoneal endometriosis (PE) | 16 | 33 | 26–46 |
Ovarian endometriosis (OE) | 10 | 35.5 | 26–47 |
Deeply infiltrating endometriosis (DIE) | 10 | 36.5 | 27–47 |
Cesarean section scar endometriosis (CC) | 14 | 34 | 24–42 |
HV | 24 | 33 | 18–57 |
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Sobstyl, A.; Mertowska, P.; Mertowski, S.; Tarkowski, R.; Dudziński, D.; Kotowski, M.; Bojarski, K.; Stelmach, B.; Chermuła, B.; Brązert, M.; et al. Expression of Toll-like Receptors on Lymphocyte Subpopulations and Their Soluble Forms in Serum and Urine of Women with Endometriosis. Cells 2025, 14, 1273. https://doi.org/10.3390/cells14161273
Sobstyl A, Mertowska P, Mertowski S, Tarkowski R, Dudziński D, Kotowski M, Bojarski K, Stelmach B, Chermuła B, Brązert M, et al. Expression of Toll-like Receptors on Lymphocyte Subpopulations and Their Soluble Forms in Serum and Urine of Women with Endometriosis. Cells. 2025; 14(16):1273. https://doi.org/10.3390/cells14161273
Chicago/Turabian StyleSobstyl, Anna, Paulina Mertowska, Sebastian Mertowski, Rafał Tarkowski, Dominik Dudziński, Michał Kotowski, Krzysztof Bojarski, Bogusława Stelmach, Błażej Chermuła, Maciej Brązert, and et al. 2025. "Expression of Toll-like Receptors on Lymphocyte Subpopulations and Their Soluble Forms in Serum and Urine of Women with Endometriosis" Cells 14, no. 16: 1273. https://doi.org/10.3390/cells14161273
APA StyleSobstyl, A., Mertowska, P., Mertowski, S., Tarkowski, R., Dudziński, D., Kotowski, M., Bojarski, K., Stelmach, B., Chermuła, B., Brązert, M., & Grywalska, E. (2025). Expression of Toll-like Receptors on Lymphocyte Subpopulations and Their Soluble Forms in Serum and Urine of Women with Endometriosis. Cells, 14(16), 1273. https://doi.org/10.3390/cells14161273