Complement-Mediated Disorders in Pregnancy

Chinchilla, Kana Amari; Vijayan, Madhusudan; Garcia, Bruna Taveras; Jim, Belinda

doi:10.1053/j.ackd.2020.01.002

Cited by 18 publications

(9 citation statements)

References 77 publications

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“…Mutations in genes controlling CAP activation have also been found to a variable degree underlying secondary causes of HUS, depending to a large extent on the specific cause. For example, malignant hypertension-associated HUS ( 65 – 67 ), pregnancy associated aHUS ( 68 ), and de novo TMA following transplantation have been shown to have a high frequency of underlying mutations, whereas drug induced-TMA ( 11 , 22 ) and autoimmune disease-associated HUS ( 11 , 22 ) do so much less frequently. The use of C5 inhibition in secondary TMA is of uncertain benefit with conflicting data published to date.…”

Section: Discussionmentioning

confidence: 99%

Thrombotic Microangiopathy, an Unusual Form of Monoclonal Gammopathy of Renal Significance: Report of 3 Cases and Literature Review

Filippone

Newman

et al. 2021

Front. Immunol.

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Monoclonal gammopathies result from neoplastic clones of the B-cell lineage and may cause kidney disease by various mechanisms. When the underlying clone does not meet criteria for a malignancy requiring treatment, the paraprotein is called a monoclonal gammopathy of renal significance (MGRS). One rarely reported kidney lesion associated with benign paraproteins is thrombotic microangiopathy (TMA), provisionally considered as a combination signifying MGRS. Such cases may lack systemic features of TMA, such as a microangiopathic hemolytic anemia, and the disease may be kidney limited. There is no direct deposition of the paraprotein in the kidney, and the presumed mechanism is disordered complement regulation. We report three cases of kidney limited TMA associated with benign paraproteins that had no other detectable cause for the TMA, representing cases of MGRS. Two of the cases are receiving clone directed therapy, and none are receiving eculizumab. We discuss in detail the pathophysiological basis for this possible association. Our approach to therapy involves first ruling out other causes of TMA as well as an underlying B-cell malignancy that would necessitate direct treatment. Otherwise, clone directed therapy should be considered. If refractory to such therapy or the disease is severe and multisystemic, C5 inhibition (eculizumab or ravulizumab) may be indicated as well.

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Section: Discussionmentioning

confidence: 99%

Thrombotic Microangiopathy, an Unusual Form of Monoclonal Gammopathy of Renal Significance: Report of 3 Cases and Literature Review

Filippone

Newman

et al. 2021

Front. Immunol.

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“…Activation of C5 generates C5a and C5b, and C5 inhibitor (eculizumab) prevents activation of C5 for therapeutic purpose (Jore et al, 2016). Complement-mediated disorders in pregnancy include pregnancy-associated hemolytic uremic syndrome, preeclampsia, and peripartum cardiomyopathy, and eculizumab can quench the complement cascade to attenuate the pregnancy disorders (Amari Chinchilla et al, 2020). However, lack of C5 cannot rescue the embryos from embryonic death, indicating that C5 plays a role in inhibiting embryonic lethality in Crry-deficient mice (Mao et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Early pregnancy regulates expression of complement components in ovine liver

Feng

Yang

Zhang

et al. 2021

Animal Science Journal

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Complement pathways participate in the regulation of innate immune system, and complement activation is inhibited in normal pregnancy. The liver plays key roles in the modulation of immunity and tolerance, but it is unclear that early pregnancy induces the changes in expression of complement components in the ovine maternal liver. The aim of the present study was to explore the expression of complement components in the liver using quantitative real‐time polymerase chain reaction (PCR), Western blot, and immunohistochemistry. Maternal livers were collected on Day 16 of the estrous cycle and Days 13, 16, and 25 of gestation. The results indicated that early pregnancy suppressed the expression of C1q, C1r, C1s, C2, C4a, C5b, and C9 in the maternal liver, but C3 expression was increased. In addition, C3 protein was located in the endothelial cells of the proper hepatic arteries and portal veins and hepatocytes. In summary, the downregulaltion of C1q, C1r, C1s, C2, C4a, C5b, and C9 may be involved in the suppression of complement activation, and upregulation of C3 is related to the modulation of maternal immune tolerance in ovine liver.

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“…Although pregnant women were excepted from prospective trials of eculizumab, its efficacy in CM-HUS in pregnancy was demonstrated in retrospective reports. 43 44…”

Section: Thrombotic Burden Of Hemolytic Diseases In Pregnancymentioning

confidence: 99%

Thrombosis in Pregnant Women with Hemolytic Anemia

Papadakis¹,

Brenner

2022

Semin Thromb Hemost

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Hemolytic anemias are a group of uncommon disorders affecting both genders, frequently occurring at the reproductive age. While a link between hemolysis and hypercoagulability has been suggested based on the elucidation of certain involved pathophysiological mechanisms, the extent of thrombotic risk in pregnant women with hemolytic anemia remains debatable. Due to the paucity of pregnancy-related data, risk assessment of gestations in women with hemolytic anemia is complicated. This review will highlight the latest advances in the diagnosis and management of these challenging disorders in pregnancy.

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Complement-Mediated Disorders in Pregnancy

Cited by 18 publications

References 77 publications

Thrombotic Microangiopathy, an Unusual Form of Monoclonal Gammopathy of Renal Significance: Report of 3 Cases and Literature Review

Thrombotic Microangiopathy, an Unusual Form of Monoclonal Gammopathy of Renal Significance: Report of 3 Cases and Literature Review

Early pregnancy regulates expression of complement components in ovine liver

Thrombosis in Pregnant Women with Hemolytic Anemia

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