Mannose-binding Lectin in Pregnancy Course and Outcome: Studies in healthy women and rheumatoid arthritis patients

Pregnancy is considered an immunological phenomenon since the pregnant mother needs to accommodate the fetal allograft. This requires profound changes of the maternal immune system. In this scope it has been hypothesized that the improvement of autoimmune diseases like rheumatoid arthritis (RA) is a result of adaptations of the immune system during pregnancy. The mechanism underlying this phenomenon and factors that can predict improvement or deterioration of RA are still largely unknown, but multiple hypotheses have been proposed 1-9. It has been suggested that the adaptive immunity declines during pregnancy, enabling the pregnant body to tolerate the fetus as a semi-allograft. As a consequence, it can be hypothesized that innate immunity compensates during this state of reduced adaptive immunity. Mannose-binding lectin (MBL), a complement factor of innate immunity, has been hypothesized to play a role in the clearance of pathogenic autoantibodies from the circulation, in particular those autoantibodies that lack galactose sugar residues. An increase in MBL levels during pregnancy would therefore result in decreased levels of pathogenic autoantibodies and hence may be associated with decreased disease activity, and the reverse in the postpartum period. Furthermore, if the susceptibility to RA as well as to certain adverse pregnancy outcome measures are associated with low MBL levels, the increased incidence of RA or pre-eclampsia, preterm birth and other adverse pregnancy outcome measures could be the result of shared pathogenic factors. The aim of the research described in this thesis is to determine whether MBL plays a role in healthy (pregnant) controls as well as in pregnancy-induced improvement of RA and deterioration postpartum. Moreover it is investigated whether MBL polymorphisms are a common pathogenic factor involved both in RA as well as in certain adverse pregnancy outcome measures.

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