Pre-Pregnancy Levels of Peripheral Natural Killer Cells as Markers for Immunomodulatory Treatment in Patients with Recurrent Miscarriage

  • Ruben J. Kuon
  • Franziska Müller
  • Kilian Vomstein
  • Maja Weber
  • Hannes Hudalla
  • Sabine Rösner
  • Thomas Strowitzki
  • Udo Markert
  • Volker Daniel
  • Bettina Toth
Original Article


Immunological risk factors in patients with recurrent miscarriage (RM) are discussed controversially. Abnormalities of natural killer cells (NK) have been described in RM patients. Lipid infusions are known to modulate lymphocyte subsets. The aim of this study was to identify immune parameters that predict success of treatment with lipid infusions in RM patients with elevated NK. In sum, n = 341 couples with RM were screened for established risk factors and peripheral lymphocyte subpopulations as well as uterine NK cells. We identified n = 136 patients with ≥ 2 consecutive RM and elevated NK. So far, n = 40 RM patients with NK disorders were treated with lipid infusions starting at positive pregnancy test, every 2 weeks until 12 + 0 weeks of gestation (GW) or miscarriage. The pre-pregnancy immune diagnostics in idiopathic RM (iRM) patients with ongoing pregnancy were compared to the group with miscarriages and healthy controls (n = 15). Pre-pregnancy immune diagnostics differed significantly between the groups, with significant higher levels of peripheral NK (% and /µL) in iRM patients who miscarried again compared to controls (p = 0.0035 and p = 0.0019). Furthermore, iRM patients show lower percentages of CD3+ lymphocytes than healthy controls (p = 0.0049). In n = 22/40 (55%) patients, pregnancy is ongoing >12 + 0 GW. RM patients with very high pre-pregnancy peripheral NK (pNK) lymphocytes might not benefit from lipid infusions. Pre-pregnancy immunomodulatory treatment in RM patients might be helpful to lower pNK levels and establish an immune environment which is supportive for fetal development.


Recurrent miscarriage Natural killer cells Lipid infusion Immune diagnostics 



We would like to acknowledge the skillful technical assistance of Martina Kutsche-Bauer, Regina Seemuth, Marita Heilke, Anja Brüchig, Silja Petersen, and Lisa Michel.

Compliance with Ethical Standards

Conflict of Interest


Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.


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Copyright information

© L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland 2017

Authors and Affiliations

  • Ruben J. Kuon
    • 1
  • Franziska Müller
    • 1
  • Kilian Vomstein
    • 1
  • Maja Weber
    • 2
  • Hannes Hudalla
    • 3
    • 4
  • Sabine Rösner
    • 1
  • Thomas Strowitzki
    • 1
  • Udo Markert
    • 2
  • Volker Daniel
    • 5
  • Bettina Toth
    • 6
  1. 1.Department of Gynecological Endocrinology and Fertility DisordersRuprecht-Karls University HeidelbergHeidelbergGermany
  2. 2.Placenta-Lab, Department of ObstetricsUniversity Hospital JenaJenaGermany
  3. 3.Department of NeonatologyRuprecht-Karls University HeidelbergHeidelbergGermany
  4. 4.Department of Pediatric Newborn Medicine, Brigham and Women’s HospitalHarvard Medical SchoolBostonUSA
  5. 5.Transplantation-Immunology, Institute of ImmunologyRuprecht-Karls University HeidelbergHeidelbergGermany
  6. 6.Gynecological Endocrinology and Reproductive MedicineMedical University InnsbruckInnsbruckAustria

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