Emerging Treatment Models in Rheumatology: Antiphospholipid Syndrome and Pregnancy: Pathogenesis to Translation

Abrahams, Vikki M.; Chamley, Lawrence W.; Salmon, Jane E.

doi:10.1002/art.40136

Cited by 79 publications

(87 citation statements)

References 97 publications

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“…25,26 The PPV of gestational age at delivery recorded on birth certificates has been found to be 98-100%. 28 We did not make adjustments by parity for diseases other than RA and SLE because of the number of deliveries assessed. Information on this diagnosis is unavailable as there is no associated ICD-9-CM code, however.…”

Section: Strengths and Limitationsmentioning

confidence: 99%

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Preterm birth phenotypes in women with autoimmune rheumatic diseases: a population‐based cohort study

Kolstad

Mayo

Chung

et al. 2019

BJOG

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Objective To investigate preterm birth (PTB) phenotypes in women with different autoimmune rheumatic diseases in a large population‐based cohort. Design Retrospective cohort study. Setting California, USA. Population All live singleton births in California between 2007 and 2011 were analysed. Patients with autoimmune disease at delivery were identified by International Classification of Diseases, Ninth Revision , Clinical Modification (ICD‐9‐CM), codes for systemic lupus erythematosus (SLE), systemic sclerosis (SSc), rheumatoid arthritis (RA), polymyositis/dermatomyositis (DM/PM), and juvenile idiopathic arthritis (JIA). Methods Maternally linked hospital and birth certificate records of 2 481 516 deliveries were assessed (SLE n = 2272, RA n = 1501, SSc n = 88, JIA n = 187, DM/PM n = 38). Multivariable Poisson regression models estimated the risk ratios (RRs) for different PTB phenotypes (relative to term deliveries) for each autoimmune disease compared with the general obstetric population, adjusting for maternal age, race/ethnicity, body mass index, smoking, education, payer, parity, and prenatal care. Main outcome measures Preterm birth (PTB) was assessed overall (20–36 weeks of gestation) and by subphenotype: preterm prelabour rupture of membranes (PPROM), spontaneous birth, or medically indicated PTB. The risk of PTB overall and for each phenotype was partitioned by gestational age: early (20–31 weeks of gestation) and late (32–36 weeks of gestation). Results Risks for PTB were elevated for each autoimmune disease evaluated: SLE (RR 3.27, 95% CI 3.01–3.56), RA (RR 2.04, 95% CI 1.79–2.33), SSc (RR 3.74, 95% CI 2.51–5.58), JIA (RR 2.23, 95% CI 1.54–3.23), and DM/PM (RR 5.26, 95% CI 3.12–8.89). These elevated risks were observed for the majority of PTB phenotypes as well. Conclusions Women with systemic autoimmune diseases appear to have an elevated risk of various PTB phenotypes. Therefore, preconception counselling and close monitoring during pregnancy is crucial. Tweetable abstract This study found that women with systemic autoimmune diseases have an elevated risk of preterm birth phenotypes.

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Section: Strengths and Limitationsmentioning

confidence: 99%

“…Information on this diagnosis is unavailable as there is no associated ICD-9-CM code, however. 28 We did not make adjustments by parity for diseases other than RA and SLE because of the number of deliveries assessed.…”

Section: Strengths and Limitationsmentioning

confidence: 99%

Preterm birth phenotypes in women with autoimmune rheumatic diseases: a population‐based cohort study

Kolstad

Mayo

Chung

et al. 2019

BJOG

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“…Numerous studies have modeled antiphospholipid syndrome [84] but this specific adverse pregnancy condition, oftentimes with preeclampsia, is beyond the scope of this review. The role of the complement system has been investigated in primarily two models of Stage 2 preeclampsia.…”

Section: The Complement System In Stage 2 Of Preeclampsiamentioning

confidence: 99%

The Complement System and Preeclampsia

2017

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Purpose of review Preeclampsia affects 3–4% of pregnancies with few treatment options to reduce maternal and fetal harm. Recent evidence that targeting the complement system may be an effective therapeutic strategy in prevention or treatment of preeclampsia will be reviewed. Recent findings Studies in humans confirm the safety and efficacy of C5 blockade in complement-mediated disorders of pregnancy, including preeclampsia. Animal models mimic the placental abnormalities, and/or the maternal symptoms, which characterize preeclampsia. These models in mouse and rat have defined a role for complement and its regulators in placental dysfunction, hypertension, proteinuria, endothelial dysfunction, fetal growth restriction and angiogenic imbalance, thus informing future human studies. Summary Targeting excessive complement activation, particularly the terminal complement complex (C5b-9) and C5a may be an effective strategy to prolong pregnancy in women with preeclampsia. Continued research is needed to identify the initiator(s) of activation, the pathways involved and the key component(s) in the pathophysiology to allow development of safe and effective therapeutics to target complement without compromising its role in homeostasis and host defense.

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“…In patients with APS, thrombosis may be the result of a hypercoagulable state related to the induction of a proinflammatory and procoagulant phenotype induced by a heterogeneous family of antibodies, among which anti-β2-glycoprotein I (anti-β2-GPI) antibodies are the best characterized [1][2][3][4]. In patients with APS, thrombosis may be the result of a hypercoagulable state related to the induction of a proinflammatory and procoagulant phenotype induced by a heterogeneous family of antibodies, among which anti-β2-glycoprotein I (anti-β2-GPI) antibodies are the best characterized [1][2][3][4].…”

Section: Introductionmentioning

confidence: 99%

“…Anti-phospholipid syndrome (APS) is characterized by arterial and/or venous thrombosis and pregnancy morbidity. In patients with APS, thrombosis may be the result of a hypercoagulable state related to the induction of a proinflammatory and procoagulant phenotype induced by a heterogeneous family of antibodies, among which anti-β2-glycoprotein I (anti-β2-GPI) antibodies are the best characterized [1][2][3][4].…”

Section: Introductionmentioning

confidence: 99%

Tissue factor over-expression in platelets of patients with anti-phospholipid syndrome: induction role of anti-β2-GPI antibodies

Capozzi

Manganelli

Riitano

et al. 2019

Clinical and Experimental Immunology

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Anti-phospholipid syndrome (APS) is characterized by arterial and/or venous thrombosis and pregnancy morbidity. It is well known that in these patients thrombosis may be the result of a hypercoagulable state related to anti-β2glycoprotein I (β2-GPI) antibodies. Moreover, platelets may play a role in thrombotic manifestations by binding of anti-β2-GPI antibodies. Platelets express tissue factor (TF), the major initiator of the clotting cascade, after activation. We primarily analyzed whether anti-β2-GPI antibodies may trigger a signal transduction pathway leading to TF expression in human platelets. Platelets from healthy donors were incubated with affinity purified anti-β2-GPI antibodies for different times. Platelet lysates were analyzed for phospho-interleukin-1 receptor-associated kinase 1 (IRAK), phospho-p65 nuclear factor kappaB (NF-κB) and TF by Western blot. IRAK phosphorylation was observed as early as 10 min of anti-β2-GPI treatment, with consequent NF-κB activation, whereas TF expression, detectable at 45 min, was significantly increased after 4 h of anti-β2-GPI treatment. Virtually no activation was observed following treatment with control immunoglobulin IgG. We then analyzed TF expression in platelets from 20 APS patients and 20 healthy donors. We observed a significant increase of TF in APS patients versus control subjects (P < 0·0001). This work demonstrates that anti-β2-GPI antibodies may trigger in vitro a signal transduction pathway in human platelets, which involves IRAK phosphorylation and NF-κB activation, followed by TF expression. Furthermore, ex vivo, platelets of APS patients showed a significantly increased expression of TF. These findings support the view that platelets may play a role in the pathogenesis of APS, with consequent release of different procoagulant mediators, including TF.

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Emerging Treatment Models in Rheumatology: Antiphospholipid Syndrome and Pregnancy: Pathogenesis to Translation

Cited by 79 publications

References 97 publications

Preterm birth phenotypes in women with autoimmune rheumatic diseases: a population‐based cohort study

Preterm birth phenotypes in women with autoimmune rheumatic diseases: a population‐based cohort study

The Complement System and Preeclampsia

Tissue factor over-expression in platelets of patients with anti-phospholipid syndrome: induction role of anti-β2-GPI antibodies

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