Elevated NK cell level and autoimmunity synergistically decrease uterine blood flow during early pregnancy

Abstract

To investigate if uterine blood flow pattern in pregnant women with a history of recurrent spontaneous abortion (RSA) is different between pregnant women with elevated NK cells with autoimmunity, and pregnant women with isolated NK cell elevation or autoimmunity only. Prospectively controlled. Pregnant women (between 5 to 7 weeks gestation) with a history of unexplained RSA (n=75) comprise the study group. Total 41 healthy pregnant women without history of RSA were included as controls. All RSA women were tested for auto-antibodies such as lupus anticoagulant, anti-cardiolipin antibody (IgG and IgM), anti-peroxidase antibody (IgG and IgM), and NK cell (CD3-/56+) levels (%) in peripheral blood mononuclear cells by flow cytometry. Uterine radial artery resistance index (RI) was measured by color-pulsed Doppler trans-vaginal ultrasound. Total 39 (52.0%) women with RSA have at least one autoantibodies (AA+), and 47 (62.7%) had elevated NK cells (>12%, NK+). Total 20 (26.7%) women had NK cell elevation only (NK+/AA-) and 27 (36.0%) had both NK cell elevation and autoantibodies (NK+/AA+). The mean RI of AA+ group (0.61±0.10) was significantly higher than that of normal controls (0.53±0.11) (P=0.002, one way ANNOVA). However, the mean RI of AA- group (0.57±0.08) was not different from that of normal controls. The mean RIs of both NK+/AA- (0.57±0.07), and NK+/AA+ (0.62±0.10) groups were significantly higher than that of normal controls (P=0.04 and 0.001 each, one way ANNOVA). In addition, the mean RI of NK+/AA+ group was significantly higher than that of NK+/AA- group (P=0.04, student's t-test). Women with elevated NK cell levels and autoimmunity have significantly decreased blood flow at maternal fetal junction during early pregnancy. There is a possible synergistic mechanism of NK cell immune-pathology and autoimmunity in blood flow pattern.