A review of the alternative pathway of complement and its relation to HELLP syndrome: is it time to consider HELLP syndrome a disease of the alternative pathway

Abstract

Complement is a part of the innate immune system with a critical role in host defense. Although essential for survival, when dysregulated or excessively triggered complement activation can cause tissue damage and drive inflammatory and immune disorders. The alternative pathway of complement (APC) is especially important for survival against infection and can be triggered by a variety of settings: infection, trauma, surgery, or pregnancy. This excessive drive of complement manifest distinctive hemolytic diseases like atypical hemolytic uremic syndrome (aHUS) and paroxysmal nocturnal hemoglobinuria (PNH). These diseases share phenotypic similarities to HELLP syndrome: a hypertensive disorder of pregnancy with hemolysis, elevated liver enzymes, and low platelets. In this manuscript, there will be a brief review of complement activation and a description of important regulator proteins. The review will further discuss pregnancy as a major trigger of the alternative pathway, and how diseases of the APC are treated during pregnancy. Finally, the similarities between HELLP syndrome and diseases of the APC will be examined.

Keywords:

• Alternative pathway of complement
• HELLP syndrome
• preeclampsia

Disclosure statement

RAB serves on the advisory board of Alexion and Achillion Pharmaceuticals. AV has served on a advisory board for Alexion Pharmaceuticals.

Additional information

Funding

The time for research and manuscript has been funded by NIH [RO1 HL133113], the Johns Hopkins Robert E. Meyerhoff Professorship, and the BIRCWH NIH [1K12HD085845-01].