Alternative pathway activation in pregnancy, a measured amount “complements” a successful pregnancy, too much results in adverse events

Abstract

During pregnancy, the maternal host must adapt in order to enable growth of the fetus.These changes affect all organ systems and are designed both to protect the fetus and to minimize risk to the mother. One of the most prominent adaptations involves the immune system. The semi-allogenic fetoplacental unit has non-self components and must be protected against attack from the host. This requires both attenuation of adaptive immunity and protection from innate immune defense mechanisms. One of the key innate immune players is complement, and it is important that the fetoplacental unit is not identified as non-self and subjected to complement attack. Adaptation of the complement response must, however, be managed in such a way that maternal protection against infection is not compromised. As the complement system also plays a significant facilitating role in many of the stages of a normal pregnancy, it is also important that any necessary adaptation to accommodate the semi-allogenic aspects of the fetoplacental unit does not compromise this. In this review, both the physiological role of the alternative pathway of complement in facilitating a normal pregnancy, and its detrimental participation in pregnancy-specific disorders, are discussed.

A selective alternative pathway complement inhibitor for treatment of paroxysmal nocturnal hemoglobinuria

“…However, due to the diverse nature of disease pathologies and their underlying molecular dysregulation, no single drug can serve as a universal cure. Moreover, complex diseases with complement contributions, such as preeclampsia, Alzheimer's disease, and some forms of cancer, will likely require combination therapies (35,44). Such therapies would greatly benefit from therapeutics with different, complementary modes of action, such as SH-01.…”

Immune microenvironment dynamics in breast cancer during pregnancy: impact of gestational age on tumor-infiltrating lymphocytes and prognosis

“…As the pregnancy progresses, the proportion of tumors with high/moderate TILs and FOXP3+ TILs decrease, suggesting a potential shift in the immune landscape and immune tolerance mechanisms. During pregnancy, the maternal host undergoes adaptive changes in the immune system to protect the semi-allogenic fetoplacental unit, involving attenuation of adaptive immunity and protection from innate immune defense mechanisms ( 50 ). Malignant cells can modify metabolism and signaling pathways in the TME to enhance their survival ( 51 ).…”

The complement alternative pathway in health and disease—activation or amplification?

“…Consideration of complement involvement in pregnancy‐associated disorders is dealt with by Smith‐Jackson and Harrison 45 . This review illustrates the dilemma that is faced when treating complement‐dependent disease.…”

“…Consideration of complement involvement in pregnancyassociated disorders is dealt with by Smith-Jackson and Harrison. 45 This review illustrates the dilemma that is faced when treating complement-dependent disease. Not only is complement involved in pathology, but it can also be involved in critical development processes, and the issue of how and when to treat will be crucial for successful therapy.…”