Immune Maladaptation Research Articles

The immunology of preeclampsia

The immune maladaptation hypothesis of preeclampsia is concordant with cytokine-mediated oxidative stress, chronology of endothelial activation, lipid changes, adverse effect of changing partners, and the protective effect of sperm exposure. Genetic factors may involve underlying hereditary thrombophilic disorders and hyperhomocysteinemia, essential hypertension and/or obesity, or control of the Th1/Th2 balance and thus affect the maternal response against fetal antigens. Placental ischemia and increased syncytiotrophoblast deportation are probably end-stage disease phenomena.

Etiology and pathogenesis of preeclampsia: Current concepts

The etiology of preeclampsia is unknown. At present, 4 hypotheses are the subject of extensive investigation, as follows: (1) Placental ischemia—Increased trophoblast deportation, as a consequence of ischemia, may inflict endothelial cell dysfunction. (2) Very low-density lipoprotein versus toxicity-preventing activity—In compensation for increased energy demand during pregnancy, nonesterified fatty acids are mobilized. In women with low albumin concentrations, transporting extra nonesterified fatty acids from adipose tissues to the liver is likely to reduce albumin’s antitoxic activity to a point at which very-low density lipoprotein toxicity is expressed. (3) Immune maladaptation—Interaction between decidual leukocytes and invading cytotrophoblast cells is essential for normal trophoblast invasion and development. Immune maladaptation may cause shallow invasion of spiral arteries by endovascular cytotrophoblast cells and endothelial cell dysfunction mediated by an increased decidual release of cytokines, proteolytic enzymes, and free radical species. (4) Genetic imprinting—Development of preeclampsia-eclampsia may be based on a single recessive gene or a dominant gene with incomplete penetrance. Penetrance may be dependent on fetal genotype. The possibility of genetic imprinting should be considered in future genetic investigations of preeclampsia. (Am J Obstet Gynecol 1998;179:1359-75.)

Immune maladaptation in the etiology of preeclampsia: a review of corroborative epidemiologic studies.

Genuine preeclampsia is a disease of first pregnancies. The protective effect of multiparity, however, is lost with change of partner. Also, exposure to semen provides protection against developing preeclampsia. Analogous to altered paternity, artificial donor insemination and oocyte donation are reported to result in a substantial increase of preeclampsia. Thus, epidemiologic studies strongly suggest that immune maladaptation is involved in the etiology of preeclampsia. Although the exact etiology of preeclampsia remains unknown, the conclusions derived from epidemiologic studies may have consequences for practicing physicians: 1) according to the primipaternity concept, a multiparous women with a new partner should be approached as being a primigravid women; 2) artificial donor insemination and oocyte donation are associated with an increased risk of developing pregnancy-induced hypertensive disorders; 3) a more or less prolonged period of sperm exposure provides a partial protection against pregnancy-induced hypertensive disorders. In the 1990s, all women with changing partners are strongly advised to use condoms to prevent sexually transmitted diseases. However, a certain period of sperm exposure within a stable relation, when pregnancy is aimed for, is associated with a partial protection against preeclampsia.

Pathogenesis of preeclampsia: a comprehensive model.

The objective of this review was to provide a comprehensive and practical concept on the pathogenesis of preeclampsia on the basis of the currently available scientific evidence. A MEDLINE search was performed of English-language articles published between 1966 and 1997, supplemented with references cited in relevant research articles. Using our data sources, we developed a scheme describing the sequence of events between implantation and the time of manifest clinical disease characterized by generalized endothelial cell dysfunction. A yet unidentified toxic circulating factor released by the ischemic placenta, is held responsible for the impaired endothelial cell function. Particularly, epidemiological studies point to a concept in which immune maladaptation to the fetal allograft plays a key role in causing defective placentation leading to placental ischaemia. The incidence of preeclampsia in sisters and daughters of women who had had preeclampsia is raised. Disease states with vascular involvement, like chronic hypertension and diabetes mellites, are associated with an increased risk for preeclampsia. Recently subclinical abnormalities in hemostasis, metabolism and volume homeostasis have been described in patients with a history of preeclampsia. Placental ischemia secondary to defective placentation, a prerequisite for the development of preeclampsia, has a multifactorial origin consisting of three major components: immune maladaptation, genetic predisposition, and vascular mediated factors. Probably, a summation of these factors will determine whether a pregnant woman is to develop the syndrome. The recently described subclinical abnormalities in hemostasis, metabolism, and vascular function in patients with a history of preeclampsia might give the clinician the opportunity to reduce the recurrence risk by pharmacotherapeutic intervention.