Antibodies during pregnancy : Aspects on complications during pregnancy and complications related to transfusion

Sammanfattning: The fetus acquires half of its genetic infonnation from the father and represents a foreign graft in pregnancy. The overall mechanisms contributing to immunologic tolerance and successful pregancy still are an enigma. Accumulating results of immunologic research, however, offer an explanation for many events in pregnancy. The purpose of this study was to investigate immune responses in pregnancy, antibody production, fetomatemal transport of antibodies and their impact on complications during pregnancy and complications related to transfusion.The human immune system exerts its effects by cellular (T-cell mediated, Thl dominated) and humoral (antibody mediated, Th2-dominated) immunity. Cellular immunity provides protection against foreign and infected cells while humoral immunity protects against extracellular pathogens. According to the Thl/Th2 paradigm successful pregnancy is Th2 dominated. We found elevated numbers of cytokine secreting cells of both Th-1 and Th-2 type in normal pregnancy and recurrent spontaneous abortions. However, the overall immune response may functionally be Th2-dominated and possibly more pronounced locally, at the fetomaternal interface.The fetus, despite the fetomaternal barrier, represents a huge antigenic challenge for the mother. As a consequence, the mother produces a variety of antibodies, directed against fetal antigens of paternal origin. In pregnancy, only IgG antibodies are, by an active process, transported from the mother to the fetus. Normal fetal IgG concentrations during pregnancy were established, as reliable published data were rare. The calculated regression line for f/m IgG ratio can be considered an accurate description of the nonnal IgG distribution in the fetus in relation to the mother.It has been proposed that lgG transport may be decreased in Rh (D) immunizations. According to this hypothesis, the impaired transport of anti-D should represent a protective mechanism against hemolytic disease of the newborn. Our studies gave controversial results. We could partly confirm the hypotesis as measured by correlation of fetal IgG vs maternal anti-D concentrations and fetal/newborn hemoglobin concentrations. In contrast we did not find significantly lower fetal IgG concentrations in Rh (D) immunizations compared with normal pregnancy.The lgG subclass composition of anti-D in Rh (D) immunizations was studied by an established test performed in microtiter plates and our own novel gel-test. Comparison of these two test showed that the same IgG subclasses of anti-D were detected by both methods. However, the gel-test had two major advantages: it was much more rapid and most importantly, interpretation of results was easier than with the microtitre assay.Women immunized during pregnancy may later become blood donors. The concentration of antibodies produced during pregnancy may afterwards decrease. However, the antibodoes do not disappear, and may thereby cause post-transfusion reactions. It has been reported that granulocyte- and I-ILA antibodies may cause transfusion-related acute lung injury (TRALI). TRALI is a rare but life-threatening complication of blood transfusion. Data from our study suggest that multiparous donors(≥ 3 pregnancies) should donate only plasma for fractionation or, if cell concentrates must be used, they shouid be washed before transfusion.