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

Girardi, Guillermina; Berman, Jessica; Redecha, Patricia; Spruce, Lynn A.; 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.

doi:10.1172/jci218817c1

Cited by 69 publications

(124 citation statements)

References 1 publication

Supporting

Mentioning

122

Contrasting

Order By: Relevance

“…[8,24,47] Apart from their role in host defense, uncontrolled or excessive production of anaphylatoxins have been implicated in the pathogenesis of inflammatory diseases including sepsis, [7,36,57] asthma, [28,37] rheumatoid arthritis, [22,35] adult respiratory distress syndrome, [50] ischemia reperfusion injury, [59] and pregnancy loss. [18] Preterm birth is one of the leading causes of neonatal mortality and morbidity. [14,33,49] A solid body of clinical and epidemiologic evidence implicates systemic and intrauterine infection in the etiology of premature labor and delivery.…”

Section: Introductionmentioning

confidence: 99%

Anaphylatoxins in preterm and term labor

Soto

Romero

Richani

et al. 2005

Journal of Perinatal Medicine

View full text Add to dashboard Cite

Objective: The complement system plays a central role in the first line of defense against invading pathogens, and its activation involves the release of potent proinflammatory mediators such as anaphylatoxins C3a, C4a and C5a. The aim of this study was to determine whether differences existed in maternal plasma anaphylatoxin concentrations between patients with term and preterm parturition. Study design: A cross-sectional study was designed to determine the plasma anaphylatoxin concentrations in 296 pregnant women in the following groups: 1) normal pregnancy between 20-36 6/7 weeks (ns64); 2) term not in labor (ns70); 3) term in labor (ns60); and 4) preterm labor with intact membranes (ns102). Women with preterm labor were classified into: a) term delivery (ns24); b) preterm delivery without intra-amniotic infection (IAI) (ns62); and c) preterm delivery with IAI (ns16). Concentrations of C3a, C4a and C5a were determined by ELISAs. Statistical analysis was conducted with nonparametric methods. Results: 1) The median plasma C5a concentration was lower in women at term in labor than in those not in labor (P-0.001). In contrast, there were no differences in plasma C3a and C4a concentrations between the two groups (P)0.05). 2) Among patients with preterm labor, those with IAI had a higher median plasma C5a concentration than those without IAI and those who delivered at term (post-hoc tests P-0.001 and Ps0.01, respectively). When comparing the preterm labor subgroups with normal pregnancy, only women with preterm delivery and IAI had a median plasma C5a concentration higher than that of normal pregnant women (Kruskal-Wallis P-0.001, post hoc test P-0.001). There was no difference in the plasma C4a concentration among patients with preterm labor. The median plasma C3a concentration in patients with preterm labor with IAI was higher than in those without IAI (Kruskal-Wallis Ps0.01, and post-hoc test Ps0.005). There was no difference in the plasma C3a concentrations between women with preterm labor who delivered at term and those with preterm delivery, with or without IAI. In addition, no differences were observed in the median plasma C3a concentration between women with normal pregnancy and those in each of the preterm labor subgroups. Conclusions:The maternal plasma concentration of anaphylatoxin C5a is increased in women with preterm labor and IAI, but not in spontaneous labor at term.

show abstract

Section: Introductionmentioning

confidence: 99%

Anaphylatoxins in preterm and term labor

Soto

Romero

Richani

et al. 2005

Journal of Perinatal Medicine

View full text Add to dashboard Cite

show abstract

“…Predictors of Pregnancy outcome in systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) (PROMISSE) study [6][7][8][9][10][11] was conducted at New York. The PROMISSE study is an observational study of 700 pregnant patients, enrolled at nine major clinical centers.…”

Section: Discussionmentioning

confidence: 99%

Antiphospholipid Syndrome as a Cause of Recurrent Pregnancy Loss: 3 Case Reports and Successful Outcome

Hoque

Rashid²,

Khanam

et al. 2016

Bangladesh J Obstet Gynaecol

View full text Add to dashboard Cite

Recurrent pregnancy loss is common problem now a days and is commonly found in our daily practice.There are so many causes that are established as causative factors for recurrent pregnancy loss. Among them systemic causes includes uncontrolled diebetes mellitus, uncontrolled chronic hypertension, hypothyroidism and local causes includes uterine polyp, uterine fibroid, cervical incompetency etc. Anti-phospholipid syndrome has recently been found to be one of the causes for recurrent pregnancy loss and we have not yet enough study in our country regarding this problem that causes recurrent pregnancy loss. Pregnancy with Anti-phospholipid Syndrome (APS) is rare and it is one of the important factor that causes recurrent pregnancy loss at any trimester of pregnancy. Early diagnosis and pre-conceptional precaution for prevention of recurrent pregnancy loss is essential to deliver a healthy fetus in a diagnosed case of APS. Three cases of anti-phospholipid syndrome (APS) are reported here who have successfully deliverd healthy baby. All the cases were presented with the complaints of recurrent pregnancy loss.Bangladesh J Obstet Gynaecol, 2014; Vol. 29(2) : 106-110

show abstract

“…• aPL, via TLR-4 and MyD88, induce trophoblasts to secrete IL-1β and IL-8 [24] • Downstream of MyD88, IL-1β secretion is mediated by uric acid, which in turn activates NLRP3 inflammasome to process IL-1β [25] • Trophoblast inflammation is driven by aPL induced miR-146a-3p and uric acid which activate TLR-8 and the NLRP3 inflammasome in trophoblasts [26] • Decidual stromal cells treated with a β2GPI-dependent aPL monoclonal antibody, express an upregulation of genes involved in the inflammatory response [27,28] In vivo models:…”

Section: Pathogenesismentioning

confidence: 99%

Obstetric Anti-phospholipid Syndrome: State of the Art

et al. 2018

View full text Add to dashboard Cite

The pathogenesis of ob-APS is multifactorial, including placental infarctions, infiltration of inflammatory cells that cause acute and chronic inflammation, leading to uncontrolled inflammation and poor pregnancy outcomes. A preconception counseling and a patient-tailored treatment are fundamental to improve maternal and fetal outcomes. Thanks to conventional treatment, based on low-dose aspirin and heparin, 70% of women with ob-APS can have successful pregnancies. Women with positive anti-phospholipid antibodies (aPL) without clinical manifestations ("aPL carriers") or with obstetric manifestation not fulfilling ob-APS criteria need to be further investigated in order to assess their best management. Great interest has been given to drugs that could interact in the pathophysiological mechanisms, such as hydroxychloroquine, statins, and eculizumab. These drugs could be considered for patients refractory to conventional therapy.

show abstract

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

Cited by 69 publications

References 1 publication

Anaphylatoxins in preterm and term labor

Anaphylatoxins in preterm and term labor

Antiphospholipid Syndrome as a Cause of Recurrent Pregnancy Loss: 3 Case Reports and Successful Outcome

Obstetric Anti-phospholipid Syndrome: State of the Art

Contact Info

Product

Resources

About