The number of peripheral blood Natural Killer cells cannot be applied as a therapeutic index for immunological abnormalities in unexplained Recurrent Miscarriage

Abstract Background The role of autoantibodies in recurrent miscarriage (RM) is unclear. Commonly studied autoimmune markers in RM include anti-nuclear (ANA), thyroid peroxidase (TPO-Ab), and anti-thyroid globulin antibodies (Tg-Ab) and peripheral blood natural killer (pbNK) cells. The correlation between autoimmune markers (TPO-Ab, Tg-Ab, ANA) and pbNK cells in women with unexplained recurrent miscarriage (uRM) is unexamined. Because NK cells are associated with the adaptive immune response, we hypothesized that the change in pbNK cell number might be a result of the immune response to autoimmunity in women with RM rather than a cause of RM. We aimed to explore whether the pbNK count is significantly different in women testing positive than in those testing negative for autoantibodies. Methods The clinical data and performed pbNK cell measurements of patients who visited the specialist clinic for RM of the First Affiliated Hospital between May 2014 and August 2021 were analyzed. Eligible patients were divided into two groups: High-pbNK group (n=118) and Normal-pbNK group (n=184). Results The positive rates of TPO-Ab in High-pbNK group were significantly higher than in Normal-pbNK group (20.3% vs. 10.9%, p=0.04), and the positive rates of ANA in Normal-pbNK group were significantly higher than in High-pbNK group (22.3% vs. 11.9%, p=0.02). There was a statistically significant positive association between TPO-Ab positivity and high pbNK cells (p=0.016, OR=5.097, 95% CI 1.356–19.159), while there was a statistically significant negative association between ANA positivity and high pbNK cells (p=0.013, OR=0.293, 95% CI 0.111–0.773). Conclusion Our results indicated that changes in pbNK cell count are a result of the miscarriage-associated autoimmune response rather than a causal factor for RM. Hence, the increased number of pbNK cells cannot be applied as a therapeutic index for immunological abnormalities in patients with uRM.