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Cited by 594

The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.

Complement C5a receptors and neutrophils mediate fetal injury in the antiphospholipid syndrome

Open access
Girardi, Guillermina, Berman, Jessica, Redecha, Patricia, Spruce, Lynn, Thurman, Joshua M., Kraus, Damian, Hollmann, Travis J., Casali, Paolo, Caroll, Michael C., Wetsel, Rick A., Lambris, John D., Holers, V. Michael, Salmon, Jane E.·2003·Journal of Clinical Investigation

Abstract

Antiphospholipid syndrome (APS) is defined by recurrent pregnancy loss and thrombosis in the presence of antiphospholipid (aPL) Ab's.Currently, therapy for pregnant women with APS is focused on preventing thrombosis, but anticoagulation is only partially successful in averting miscarriage.We hypothesized that complement activation is a central mechanism of pregnancy loss in APS and tested this in a model in which pregnant mice receive human IgG containing aPL Ab's.Here we identify complement component C5 (and particularly its cleavage product C5a) and neutrophils as key mediators of fetal injury, and we show that Ab's or peptides that block C5a-C5a receptor interactions prevent pregnancy complications.The fact that F(ab)′2 fragments of aPL Ab's do not mediate fetal injury and that C4-deficient mice are protected from fetal injury suggests that activation of the complement cascade is initiated via the classical pathway.Studies in factor B-deficient mice, however, indicate that alternative pathway activation is required and amplifies complement activation.In contrast, activating FcγRs do not play an important role in mediating aPL Ab-induced fetal injury.Our findings identify the key innate immune effectors engaged by pathogenic autoantibodies that mediate poor pregnancy outcomes in APS and provide novel and important targets for prevention of pregnancy loss in APS.

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Cites

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Research works printed but not linked: 7

  1. Stephenson, 1994, Fertil. Steril., 66, 24
  2. Shin, 1996, Biomembranes., 4, 123
  3. Li, 2000, Eur. J. Immunol., 30, 2015, 10.1002/1521-4141(200007)30:7<2015::AID-IMMU2015>3.0.CO;2-5 · doi:10.1002/1521-4141(200007)30:7<2015::aid-immu2015>3.0.co;2-5
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Metadata

Authors
Girardi, G., Berman, J., Redecha, P., Spruce, L., Thurman, J. M., Kraus, D., Hollmann, T. J., Casali, P., Caroll, M. C., Wetsel, R. A., Lambris, J. D., Holers, V. M., & Salmon, J. E.
Venue
Journal of Clinical Investigation
Published
2003-12-01
Volume
112
Issue
11
Pages
1644-1654
ISSN
0021-9738 (ISSN-L)
OpenAlex
W4239387674
Cited by
594
References
49
FWCI
15.72
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Complement C5a receptors and neutrophils mediate fetal injury in the antiphospholipid syndrome. https://app.cochat.ai/papers/10.1172/jci200318817
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Girardi, G., Berman, J., Redecha, P., Spruce, L., Thurman, J. M., Kraus, D., Hollmann, T. J., Casali, P., Caroll, M. C., Wetsel, R. A., Lambris, J. D., Holers, V. M., & Salmon, J. E. (2003). Complement C5a receptors and neutrophils mediate fetal injury in the antiphospholipid syndrome. Journal of Clinical Investigation. https://doi.org/10.1172/jci200318817

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.