Inverse association between peripheral natural killer cells and thyroid autoimmunity in cases of miscarriage: Evidence from a cross-sectional study

Objective To examine the association between the percentage of peripheral natural killer cells and thyroid autoimmunity in women with a history of miscarriage and assess whether B-cells mediate this association. Methods This retrospective cross-sectional study was conducted on 927 women with a history of miscarriage treated at the Affiliated Hospital of Guizhou Medical University (2021–2023). Peripheral T-cell, B-cell, and natural killer cell subsets and thyroid antibodies were assessed. Multivariable logistic regression, restricted cubic splines, and mediation analyses were performed. Results Women with thyroid autoimmunity had lower percentage of peripheral natural killer cells and higher percentage of B-cells than those without thyroid autoimmunity (both p < 0.001). The percentage of peripheral natural killer cells demonstrated a consistent inverse association with thyroid autoimmunity after adjustment (adjusted odds ratios: 0.00; 95% confidence interval: 0.00–0.02; all p < 0.001). Restricted cubic spline analysis indicated a nonlinear dose–response relationship that was stronger in women aged ≥35 years and in those without recurrent miscarriages. B-cells partially mediated the association between the percentage of peripheral natural killer cells and thyroid autoimmunity (31.4% of the total effect; ab = −0.166; p < 0.001). Conclusion Lower percentage of peripheral natural killer cells is linked to higher odds of thyroid autoimmunity in women with a history of miscarriage, and B-cells partly explain this relationship, supporting the use of peripheral immune profiling to identify thyroid autoimmunity risk.