Endometriosis Pathophysiology

Women with endometriosis show a defect in natural killer activity resulting in a decreased cytotoxicity to autologous endometrium

Oosterlynck DJ, Cornillie FJ, Waer M, Vandeputte M, Koninckx PR

Published July 1991 Fertility and Sterility, 56(1), 45-51
DOI 10.1016/s0015-0282(16)54414-8 PMID 2065804

RRM Academy Synopsis

Women with endometriosis have weaker natural killer cell activity

In a prospective laboratory study of 34 women in Belgium, natural killer cell activity fell as endometriosis grew more severe. Immune cells from women with endometriosis also killed their own endometrial cells less well. Donor cells showed a smaller weakness against the same endometrial cells.

Key Findings

  • Against K562 target cells, which measure natural killer activity, specific lysis fell from 62.2% without endometriosis to 52.4%, 44.9% and 39.8% at stages I, II and III to IV (P = 0.002).
  • Specific lysis of the women's own endometrial cells fell across the same four groups: 21.0%, 12.4%, 6.1% and 5.2% (ANOVA, P = 0.0001).
  • Lymphocytes from a male control donor, tested against the women's endometrial cells, produced 18.7%, 22.3%, 11.2% and 11.7% specific lysis across the four groups (ANOVA, P = 0.01).
  • In five women, removing natural killer cells with an anti-Leu-11b antibody cut K562 lysis from 61.4% to 6.9% and autologous endometrial lysis from 18.4% to 3.1%.
  • Total white blood cell counts did not explain the lower activity, and flow cytometry showed no significant alteration in the percentages of lymphocyte subsets, including natural killer cells.

Interpretation

Natural killer cells are immune cells that defend the body against virus-infected and tumor cells. The study tested blood and endometrial samples from 34 women at one Belgian university hospital. A surgeon scored endometriosis blind to the immune results. The tests ran in vitro, meaning in cultured cells. In each woman, the K562 results and the endometrial results moved together (Spearman, P = 0.001). The authors note that it must still be established whether the natural killer defect comes first or follows the inflammation that endometriosis produces.

RRM Context

Restorative reproductive medicine treats endometriosis as a disease with its own biology and looks for the cause behind pain and infertility. Immune function is one part of that biology. The authors planned to retest these women 3 to 4 months after laser excision of the lesions, to learn whether the natural killer defect is primary.

Abstract

Objective

The role of natural killer (NK) cells in the decreased cellular immunity of women with endometriosis was investigated.

Design, Setting, and Patients

Thirty-four women were investigated prospectively before a CO2-laser laparoscopy for infertility and/or pain at the University Hospital Gasthuisberg. Endometriosis was scored blindly.

Main Outcome Measures

The cytotoxicity, directed against the endometrium, was mediated by NK cells because this cytotoxicity could be removed by treating the effector cells with the NK-specific anti-Leu-11b monoclonal antibody. Consequently, we evaluated prospectively in those women the lymphocyte-mediated cytotoxicity toward NK sensitive (K562-assay) and autologous endometrial target cells.

Results

The NK activity (K562-assay) and the cytotoxicity against autologous endometrial cells were similarly decreased in women with endometriosis and correlated with the severity of the disease. Using heterologous effector cells, the decreased chromium release in women with endometriosis was less pronounced but still present.

Conclusion

The decreased cytotoxicity to endometrial cells in women with endometriosis is mainly because of a defect in NK activity but is also partially because of a resistance of the endometrium to NK cytotoxicity.

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Endometriosis › Pathophysiology › Inflammation and Immunology · Genetics and Immunology › Reproductive Immunology › Implantation Immunology · General Gynecology › Pelvic Pain › Chronic Pelvic Pain
Didier J. Oosterlynck, Freddy J. Cornillie, Mark Waer, Michel Vandeputte, Philippe R. Koninckx
D Oosterlynck, F Cornillie, M Waer, M Vandeputte, P Koninckx
PMID 2065804 2065804 DOI 10.1016/s0015-0282(16)54414-8 10.1016/s0015-0282(16)54414-8 Oosterlynck et al. 1991, Oosterlynck 1991