Active Immunisation with Partner Lymphocytes in Female Patients Who Want to Become Pregnant - Current Status

Abstract

Around 1 - 3% of all couples who try to have a child are affected by recurrent miscarriage. According to the WHO, recurrent miscarriage is defined as the occurrence of three or more consecutive miscarriages up to the 20th week of pregnancy. There are various causes of recurrent miscarriage; in many cases, the causes remain unclear, with the result that immunological factors are one of the possible causes discussed. For the mother's immune system, the embryo represents a semi-allogeneic transplant, as half of the embryo's genes are of paternal origin. In place of a conventional immune response, the embryo induces a secondary protection mechanism, which contributes to the successful implantation. When performing immunisation with partner lymphocytes, the patient receives an intradermal injection of her partner's prepared lymphocytes into the volar side of the forearm in order to induce immunomodulation with a consequently increased rate of pregnancy and live birth. A prerequisite for this procedure is that all other possible causes of sterility have been ruled out in advance. Due to the highly heterogeneous nature of the data, a significant benefit as a result of the immunisation cannot yet be clearly proven. However, there are signs that the therapy may be effective when using lymphocytes that have been extracted as short a time beforehand as possible. Overall, the treatment represents a safe, low-risk procedure. Following a detailed informative discussion with the couple regarding the chances of success and following a detailed review of the indication and contraindications, immunisation with partner lymphocytes can be discussed with the couple on a case-by-case basis - provided that all other possible causes of sterility have been ruled out in advance.

Keywords: immunisation; immunology; implantation; miscarriage; partner lymphocytes.

Fig. 1

Immunocompetent cells of the foetomaternal interface (according to 17 ). In the intervillous space, the trophoblast is in direct contact with the maternal blood. There is a special cellular immunological environment in the decidua. The individual cellular components with their most important molecules are presented here. TLR: toll-like receptor; DC: dendritic cells; TGF-beta: transforming growth factor; uNK cells: uterine natural killer cells; VEGF: vascular endothelial growth factor; IFN-gamma: interferon gamma.

Fig. 2

Major histocompatibility complex (MHC). The HLA (human leukocyte antigen) system is located on the short arm of chromosome 6 and is also known as the major histocompatibility complex (MHC). The typical MHC genes are divided into two regions, which code two classes of HLA molecules: HLA Class I (HLA-A, -B, -C), which are found on all nucleated somatic cells and HLA Class II (HLA-DR, -DQ, -DP), which are found only on antigen-presenting cells. The HLA Class III molecules include complement factors, which are involved in the non-specific immune defence. The overall HLA complex comprises around 4000 kilobases (Kb) and is very polymorphic, i.e. there are several genetic variants (alleles) for most gene loci. Source: Zentrum für Humangenetik und Laboratoriumsdiagnostik (MVZ) [Center for Human Genetics and Laboratory Diagnostics (AHC)], Dr. Hirv, Dr. Bangol, Martinsried.

Abb. 1

Immunkompetente Zellen der fetomaternalen Grenzzone (nach 17 ). Der Trophoblast steht im intervillösen Raum in direktem Kontakt mit dem maternalen Blut. In der Dezidua findet sich ein spezielles zelluläres immunologisches Milieu. Die einzelnen zellulären Komponenten mit ihren wichtigsten Molekülen sind hier dargestellt. TLR: Toll-like-Rezeptor; DC: dendritische Zellen; TGF-beta: Transforming Growth Factor; uNK-Zellen: uterine natürliche Killerzellen; VEGF: Vascular endothelial Growth Factor; IFN-gamma: Interferon-gamma.

Abb. 2

Haupthistokompatibilitätskomplex (MHC). Das HLA-(Humanes-Leukozyten-Antigen-)System ist auf dem kurzen Arm von Chromosom 6 lokalisiert und wird auch als Haupthistokompatibilitätskomplex (Major Histocompatibility Complex, MHC) bezeichnet. Die klassischen MHC-Gene sind in 2 Regionen unterteilt, die 2 Klassen von HLA-Molekülen kodieren: HLA-Klasse I (HLA-A, -B, -C), die sich auf allen kernhaltigen Körperzellen befinden, und HLA-Klasse II (HLA-DR, -DQ, -DP), die sich nur auf antigenpräsentierenden Zellen befinden. Zu den HLA-Klasse-III-Molekülen zählen Komplementfaktoren, die an der unspezifischen Immunabwehr beteiligt sind. Der gesamte HLA-Komplex umfasst ca. 4000 Kilobasen (Kb) und ist sehr polymorph, d. h. für die meisten Genorte existieren mehrere genetische Varianten (Allele).