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Genetic defects in immune system linked to pre-eclampsia

Analysis of a study published in a science journal   |   By Dr Philippa Brice   |   Published 26 March 2011
Study: Mutations in Complement Regulatory Proteins Predispose to Preeclampsia: A Genetic Analysis of the PROMISSE Cohort
By: Salmon J.E. et al. (10 authors total)
In: PLoS Medicine
Link: http://dx.doi.org/10.1371/journal.pmed.1001013
What this study set out to do:

Test the theory that genetic factors involved in abnormal control of complement, a key protein mediator of the immune response, also predispose to pre-eclampsia and miscarriage during pregnancy. 

How they went about it:

Genes for three proteins involved in the regulation of complement were sequenced and analysed from two groups of women who had developed pre-eclampsia: ‘healthy’ patients, and those with the autoimmune disorders systemic lupus erythematosus or antiphospholipid antibodies - both of which involve tissue damage due to complement. A control group without pre-eclampsia was also tested. 

Outcome:

Mutations in the three genes were found in seven out of 40 pre-eclampsia cases with autoimmune disease (18%), and in five out of 59 pre-eclampsia cases without autoimmune disease (8%). No mutations were found in 34 control group women without pre-eclampsia. 

Conclusion:

These findings support previous evidence that abnormal regulation of complement is involved in pre-eclampsia; whilst further studies are required to confirm this link, it suggests that new drugs or predictive markers for pre-eclampsia could be developed based on these immune regulatory proteins.

Our view:

Pre-eclampsia is a disease of the placenta that affects up to 10% of pregnancies and causes severe disease in 1-2% of pregnancies; it can be fatal to both the mother and baby. The precise cause of the condition is not known, but one possibility is malfunction of the immune system. These findings therefore provide a very plausible mechanism of disease, although it requires validation in larger studies, and it may also be that pre-eclampsia has multiple underlying causes of which this is only one. More research is urgently required, and possibilities for earlier diagnosis or even treatment are very important.

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