Determination of clinical cellular immune markers in women with recurrent pregnancy loss.

PROBLEM

Dysregulated natural killer (NK) immunity and T-cell immunity are associated with recurrent pregnancy loss (RPL). We aim to define clinically relevant NK and T-cell parameters for RPL and determine their cutoff values.

METHODS OF STUDY

Ninety-five women with RPL (>3) including 42 idiopathic and 53 known-etiology RPL, and 29 age-matched fertile controls were enrolled. Peripheral blood immunophenotype, NK cell cytotoxicity (NKC), and T-helper (Th) 1 and Th2 cytokine producing cell ratios (Th1/Th2) were measured using flowcytometry. The cutoff values were determined using Youden's J with likelihood ratio (LR) >2.

RESULTS

Natural killer cell percentage and NKC, TNF-α(+) Th1 cells, and TNF-α/IL-10 producing Th1/Th2 cell ratio were significantly higher in idiopathic RPL than controls. By the area under the curve (AUC) analysis, NK cell percentage (AUC = 0.691), NKC (AUC = 0.649), TNF-α(+) Th1 cells (AUC = 0.681) and Th1/Th2 cell ratio (AUC = 0.660) were highly specific for RPL. The cutoff values for NK cell percentage, NKC (E:T cell ratio 25:1), and TNF-α/IL-10 producing Th1/Th2 cell ratio are 16.1, 23.8, and 36.2%, respectively. Seventy-six percent of idiopathic RPL showed at least one of more immune abnormalities by these criteria.

CONCLUSION

Differences in NK cell percentages, NKC and Th1/Th2 cell ratio differentiated RPL from fertile controls.