Linköping University Medical Dissertations
No. 563

Immune Changes in Pregnancy

A Survey of some Immunological Variables in Normal and Complicated Pregnancies

Leif Skamris Matthiesen

Akademisk avhandling

som för avläggande av medicine doktorsexamen vid Linköpings Universitet kommer att offentligt försvaras i Berzeliussalen, Hälsouniversitetet, lördagen den 5 september 1998, kl 09.00

ABSTRACT

The maternal systemic immune response during pregnancy is only fragmentarily understood. An adequate immune response to the gestational product is of vital importance for a successful pregnancy. Research in the field of reproductive immunology could clarify whether there is a difference between the immune responses in women with normal pregnancies and women with complicated pregnancies.

The present thesis is a survey of selected immunological variables in non-pregnant women and in women with uncomplicated and complicated pregnancies. This was done by studying lymphocyte populations, the proliferative capacity of lymphocytes as stimulated with mitogens and immunomodulating drugs, the presence of IL-4 and IFN-g secreting cells, and the presence of certain autoantibodies in a low-risk pregnant population.

Normal pregnancies were characterised by decreased levels of B cells (CD19+), NK cells (CD56+), expression of the IL-2 Receptor on lymphocytes (CD25+) as well as HLA-DR+ on T cells (CD3+) and increased level of inactivated CD4+CD45RA+ T cells. Increased levels of NK cells, expression of HLA-DR on T cells and antigen activated CD4+CD45RO+ T cells was found in preeclamptic patients compared with normal pregnancies. Thus, the immunosuppression that was found in normal pregnancies was not seen in pregnancies complicated by preeclampsia.

Addition of mitogens to cell cultures in either autologous or AB serum culture media demonstrated the existence of serum and cell mediated suppressor activity. The lymphoproliferative response to mitogens was reduced during normal pregnancies, possibly mediated by PGE2 and the presence of T lymphocytes with suppressor function. The lymphoproliferative response in pregnancies complicated with severe preeclampsia was further reduced as compared with normal pregnancies.

Circulating IFN-g and IL-4 secreting cells increased during normal pregnancies. By the use of a mixed lymphocyte culture test it was found that paternal lymphocytes as stimulator-cells generated an elevated IL-4 secretion from maternal responder cells. These results indicate that the maternal immune response is shifted towards humoral immunity (TH2) by the recognition of the paternal allo-antigens, possibly to avoid maternal allo-reactivity against the fetus. The present findings also indicate that cell-mediated immunity (TH1) to antigens were allowed to occur.

The prevalence of anticardiolipin antibodies (aCL, IgG, ELISA), antinuclear antibodies (ANA, Indirect immunofluorescence) and rheumatoid factor (RF, agglutination test) in a low-risk pregnant population was low. However, there was an association, albeit weak, between ANA and women with preeclampsia.

In summary, the maternal systemic immune response is characterised by suppression and non-aggression in normal human pregnancies. In women with pregnancy complications, such as preeclarnpsia, this suppression and inactivation is only partially achieved.

Division of Obstetrics and Gynaecology, Department of Health and Environment
Faculty of Health Sciences, Linköping University
SE-581 85 Linköping, Sweden 1998

ISBN 91-7219-049-3