Obstet Gynecol Sci.  2014 May;57(3):208-215. 10.5468/ogs.2014.57.3.208.

Elevated natural killer cell levels and autoimmunity synergistically decrease uterine blood flow during early pregnancy

• Yi HJ
• Kim JH
• Koo HS
• Bae JY
• Cha SW
• Yang KM

• KMID: 1704427
• DOI: http://doi.org/10.5468/ogs.2014.57.3.208

Abstract

OBJECTIVE
To investigate whether natural killer (NK) cell and autoimmune antibody acts synergistically, by the action of autoantibodies to increase NK cell number and cytotoxicity, to decrease uterine blood flow during early pregnancy in pregnant women with a history of recurrent spontaneous abortion (RSA).
METHODS
Seventy-five pregnant women (between 5 and 7 weeks gestation) with a history of unexplained RSA were included in the study group. Forty-one pregnant women without a history of RSA were included as controls. All women with a history of RSA were tested for autoantibodies and number of peripheral blood natural killer (pbNK) cell by flow cytometry. Study populations were stratified into four groups by existence of autoantibody and degree of increase of pbNK cells. The uterine radial artery resistance index (RI) was measured by color-pulsed Doppler transvaginal ultrasound.
RESULTS
The mean RI of the autoimmune antibody-positive (AA+) group (0.63+/-0.09) was significantly higher than that of the normal control group (0.53+/-0.10, P=0.001). The mean RI of the AA+/only-NK elevated (eNK) group (0.63+/-0.09) was significantly higher than those of the only-AA+ group (0.55+/-0.07, P=0.019) and the only-eNK group (0.57+/-0.07, P=0.021).
CONCLUSION
Concurrent elevation in NK cells and autoimmunity results in decreased uterine blood flow during early pregnancy. However, the majority of cases of RSA remain unexplained and larger scale studies are needed to confirm our conclusion and to develop diagnostic and therapeutic plans for women with a history of RSA.

Keyword

Autoimmunity; Natural killer cell; Uterine blood flow

MeSH Terms

Abortion, Spontaneous
Autoantibodies
Autoimmunity*
Female
Flow Cytometry
Humans
Killer Cells, Natural*
Pregnancy*
Pregnant Women
Radial Artery
Ultrasonography
Autoantibodies

Figure

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  Fig. 1 Demographics of study population; autoimmune antibody-negative (AA-)/normal natural killer (nNK), AA-/elevated natural killer (eNK), autoimmune antibody-positive (AA+)/nNK, and AA+/eNK. RSA, recurrent spontaneous abortion; LA, lupus anticoagulant; pbNK, peripheral blood natural killer.

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  Fig. 2 Comparison of the mean uterine radial artery resistance index among autoimmune antibody-positive (AA+), autoimmune antibody-negative (AA-), and control groups. One-way ANOVA. Values are mean±SD.

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  Fig. 3 Comparison of the mean uterine radial artery resistance index among the control, autoimmune antibody-negative (AA-)/normal natural killer (nNK), AA-/elevated natural killer (eNK), autoimmune antibody-positive (AA+)/nNK, and AA+/eNK groups. One-way ANOVA. Values are mean±SD.

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  Fig. 4 Comparison of the mean uterine radial artery resistance index between before treatment with low molecular weight heparin (LMWH) and after 2 weeks of treatment with LMWH. Paired t-test. Values are mean±SD. AA-, autoimmune antibody-negative; nNK, normal natural killer; eNK, elevated natural killer; AA+, autoimmune antibody-positive.

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  Fig. 5 Summarized theories of the synergistic action between natural killer (NK) cells and autoimmune antibodies causing recurrent spontaneous abortion. APA, antiphospholipid antibody; ATA, antithyroid antibody. Kim, N.Y., et al. Am J Reprod Immunol. 65(1): p. 78-87.according to the Creative Commons Attribution License [18].

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