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Shift in Expression of HLA-G mRNA Spliceforms in Pregnancies Complicated by Preeclampsia

Irma Joosten, DVM, PhD

Martin H. Schut, MD

Petra L. M. Zusterzeel, MD, PhD

Jan C. M. hendriks, PhD

Departments of Blood Transfusion and Transplantation Immunology, Obstetrics and Gynecology, and Epidemiology and Biostatistics, University Medical Center Nijmegen, The Netherlands; Department of Obstetrics and Gynecology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands

Eric A. P. Steegers, MD, PhD

Departments of Blood Transfusion and Transplantation Immunology, Obstetrics and Gynecology, and Epidemiology and Biostatistics, University Medical Center Nijmegen, The Netherlands; Department of Obstetrics and Gynecology, Erasmus University Medical Center Rotterdam, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. e.a.p.steegers{at}erasmusmc.nl

Objective: Despite emerging data on the in vitro modulatory effects of trophoblast-associated human leukocyte antigen G (HLA-G), its in vivo function needs to be determined. Immunohistochemical studies show a decrease in protein expression of trophoblast HLA-G in preeclampsia. Such a decrease in protein might be the consequence of a shift in HLA-G mRNA spliceform pattems. In an exploratory pilot study we determined trophoblast HLA-G mRNA spliceform distribution in preeclampsia.

Methods: Placental samples were collected immediately after cesarean delivery from pregnancies complicated by preeclampsia or the syndrome hemolysis, elevated liver enzymes, and low platelet count (HELLP) and uncomplicated normotensive pregnancies as controls. HLA-G mRNA spliceform distribution was analyzed using a semiquantitative reverse transcriptase polymerase chain reaction procedure.

Results: Analysis of HLA-G spliceform distribution showed a significant increase in frequency of the G5 form encoding for a soluble HLA-G molecule in preeclampsia. This increase in G5 form was not found in pregnancies complicated by HELLP.

Conclusion: The increased frequency in the expression of the HLA-G G5 spliceform may play a role in the pathophysiology of preeclampsia, in particular through a recently suggested effect of this soluble HLA-G molecule on remodeling of the spiral arteries.

Key Words: HLA-G • preeclampsia • HELLP • RT-PCR • alternative spliceforms

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