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

  • Jacek R. Wilczyński
  • Paweł Radwan
  • Henryk Tchórzewski
  • Małgorzata Banasik
Original Article

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.

Keywords

Recurrent spontaneous miscarriage Idiopathic infertility Cytokines Paternal lymphocyte immunization 

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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Copyright information

© L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland 2012

Authors and Affiliations

  • Jacek R. Wilczyński
    • 1
    • 2
    • 3
  • Paweł Radwan
    • 1
    • 4
  • Henryk Tchórzewski
    • 5
  • Małgorzata Banasik
    • 5
  1. 1.Chair of Obstetrics and Gynecological Surgery, Department of GynecologyMedical University of LodzLodzPoland
  2. 2.Department of Gynecology“Polish Mother’s Memorial Hospital” Research InstituteLodzPoland
  3. 3.“Vita-Med” Outpatient Gynecological ClinicLodzPoland
  4. 4.“Gameta” Fertility CenterLodzPoland
  5. 5.“APC” Medical AnalysesLodzPoland

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