First steps towards a targeted immunomodulatory therapy in patients with recurrent miscarriage and elevated natural killer cells

Objective: Elevated peripheral and uterine NK cells (pNK, uNK) are associated with recurrent miscarriage (RM). Intralipids have been proposed as a treatment option to modulate NK cell dysbalance in RM patients. The aim of this study was to identify immune parameters that might predict treatment success in RM patients with elevated NK cells.

Materials and methods: In total, n = 23 RM patients with ³3 RM and elevated NK cells (n = 12 elevated pNK, n = 13 elevated uNK; n = 2 with elevation in both parameters) were treated with intralipids following a standardized treatment protocol. Intralipid therapy (8 ml 20% Intralipid® in 250 ml saline) starting with first positive pregnancy test (mean 4+2 gestational weeks (GW)) was applied every 2 weeks until 12+0 GW or miscarriage.

Results: RM patients had a history of 3.4 miscarriages (mean), 47.8% showed idiopathic RM. In n = 13/23 (56.5%) pregnancy is ongoing > 12+0 GW. So far, n = 10/23 (43.5%) miscarriages ≤12 GW occurred. Patients who miscarried had significantly higher pre-pregnancy levels of CD45+, CD3+ and CD4+ T cells (all p < 0.05).

Conclusion: A subgroup of RM patients benefits from intralipids but patients with higher pre-pregnancy CD45+, CD3+, and CD4+ lymphocytes did not profit from intralipid therapy and might need additional medication. A distinct immune profiling in RM patients including adjustment of reference ranges might be helpful to assign immomodulatory treatments to RM patients.