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Immunotherapy of Patients with Recurrent Spontaneous Miscarriage and Idiopathic Infertility: Does the Immunization-Dependent Th2 Cytokine Overbalance Really Matter?

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Archivum Immunologiae et Therapiae Experimentalis Aims and scope

Abstract

Recurrent spontaneous miscarriage (RSM) and idiopathic infertility (IIF) are partially caused by immunologic disturbances. Paternal lymphocyte immunization (PLI) is proposed for restoration of the proper Th1/Th2 balance in these patients, but still there are controversies on PLI mechanism, its efficacy and identification of patients who may benefit from this therapy. The study group consisted of n = 34 RSM and n = 42 IIF women with unexplained miscarriage or IIF. PLI was offered as a treatment in both groups. Peripheral blood lymphocyte (PBL) populations (CD3+, CD3−/CD19+, CD3+/CD4+, CD3+/CD8+, CD3−/CD16+CD56+) were studied before immunization, while PBL cytokine secretion (IFN-γ, TNF-α, IL-10, IL-5, IL-4, IL-2), before and after immunization, pre-conceptionally in both groups. The reference PBL ratio and cytokine levels were adopted from previously studied normal fertile women. PBL populations, concentration and ratio of Th1/Th2 cytokines did not differ between RSM and IIF patients. Compared to the results observed in normal fertile women the levels of IFN-γ, TNF-α and IL-2 were higher, while IL-10 lower in both RSM and IIF patients (p < 0.01). After immunization a decrease of IFN-γ (RSM and IIF groups) and IL-4 and IL-10 (RSM group) were observed, as well as an increase in TNF-α/IL-4 ratio (RSM group) (p < 0.05). No differences in Th1/Th2 concentration and ratio between patients with successful and unsuccessful pregnancy were observed. No significant correlations between success and particular cytokine concentration were observed. Concentrations of Th1/Th2 cytokines and PBL populations did not differ between RSM and IIF women. Th1 shift in both RSM and IIF patients was observed in comparison to fertile women. Treatment with PLI-induced pre-conceptionally cytokine changes which neither indicated Th2 shift nor correlated with subsequent pregnancy success.

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Abbreviations

RSM:

Recurrent spontaneous miscarriage

IL:

Interleukin

TNF-α:

Tumor necrosis factor-alpha

IFN-γ:

Interferon-gamma

IIF:

Idiopathic infertility

ART:

Artificial reproductive techniques

RIF:

Recurrent implantation failures

PLI:

Paternal lymphocyte immunization

IUI:

Intrauterine insemination

IVF-ET:

In vitro fertilization-embryo transfer

PBL:

Peripheral blood lymphocyte

BV:

Bacterial vaginosis

ACA:

Anticardiolipin antibody

ANA:

Antinuclear antibody

ASA:

Antisperm antibody

ATA:

Antithyroid antibody

TPOa:

Peroxidase antibody

TGa:

Thyroglobulin antibody

LA:

Lupus anticoagulant

LCT:

Lymphocytotoxic test

PE:

Phycoerythrin

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Acknowledgments

The study was co-financed by the Medical University of Lodz Grant no. 502-15-800.

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Authors and Affiliations

  1. Chair of Obstetrics and Gynecological Surgery, Department of Gynecology, Medical University of Lodz, Kosciuszki 4, 90-419, Lodz, Poland

    Jacek R. Wilczyński & Paweł Radwan

  2. Department of Gynecology, “Polish Mother’s Memorial Hospital” Research Institute, Lodz, Poland

    Jacek R. Wilczyński

  3. “Vita-Med” Outpatient Gynecological Clinic, Lodz, Poland

    Jacek R. Wilczyński

  4. “Gameta” Fertility Center, Lodz, Poland

    Paweł Radwan

  5. “APC” Medical Analyses, Lodz, Poland

    Henryk Tchórzewski & Małgorzata Banasik

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  1. Jacek R. Wilczyński
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  2. Paweł Radwan
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  3. Henryk Tchórzewski
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  4. Małgorzata Banasik
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Correspondence to Jacek R. Wilczyński.

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Wilczyński, J.R., Radwan, P., Tchórzewski, H. et al. Immunotherapy of Patients with Recurrent Spontaneous Miscarriage and Idiopathic Infertility: Does the Immunization-Dependent Th2 Cytokine Overbalance Really Matter?. Arch. Immunol. Ther. Exp. 60, 151–160 (2012). https://doi.org/10.1007/s00005-012-0161-6

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