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Rheumatic and musculoskeletal diseases often affect individuals of childbearing age. The incidence and prevalence of rheumatic and musculoskeletal diseases is rising. More pregnancies in patients with rheumatic and musculoskeletal diseases are anticipated and some rheumatic and musculoskeletal diseases are associated with pregnancy complications (eg, miscarriages, fetal deaths, preterm births, and hypertensive disorders in pregnancy). Despite the need to understand the use of drugs to treat rheumatic and musculoskeletal diseases in pregnancy, clinical trials in pregnancy are rare, therapeutics in pregnancy are understudied, and pregnant individuals are routinely excluded as premarketing trial participants. Data on the effectiveness and safety of disease-modifying antirheumatic drugs are most often based on post-marketing observational data. Observational studies assessing the bidirectional relationship between rheumatic and musculoskeletal diseases and pregnancy, as well as interventional studies of treatments during pregnancy, are scarce. Historical reluctance to perform studies in what was deemed an at-risk group persists in pharmaceutical companies, regulatory bodies, and ethics boards. Additionally, patients must be engaged partners, which requires trust that the research respects the needs and interests of the patient and complies with the rules intended to protect the pregnant person and the fetus from harm. In this Series paper, we share challenges we have encountered in conducting prospective cohort studies and interventional trials of postmarketing approved medications, assessing pregnancy specific outcomes in pregnant women with rheumatic and musculoskeletal diseases in the EU, the UK, and the USA. We discuss the changing landscape around trials in pregnancy and present possible solutions to our challenges.
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Ensayos Clínicos como Asunto , Complicaciones del Embarazo , Proyectos de Investigación , Humanos , Embarazo , Femenino , Complicaciones del Embarazo/tratamiento farmacológico , Complicaciones del Embarazo/epidemiología , Estudios de Cohortes , Enfermedades Reumáticas/tratamiento farmacológico , Enfermedades Musculoesqueléticas/tratamiento farmacológico , Enfermedades Musculoesqueléticas/terapia , Antirreumáticos/uso terapéuticoRESUMEN
In rheumatoid arthritis, inflammatory mediators extravasate from blood into joints via gaps between endothelial cells (ECs), but the contribution of ECs is not known. Sphingosine 1-phosphate receptor 1 (S1PR1), widely expressed on ECs, maintains the vascular barrier. Here, we assessed the contribution of vascular integrity and EC S1PR1 signaling to joint damage in mice exposed to serum-induced arthritis (SIA). EC-specific deletion of S1PR1 or pharmacological blockade of S1PR1 promoted vascular leak and amplified SIA, whereas overexpression of EC S1PR1 or treatment with an S1PR1 agonist delayed SIA. Blockade of EC S1PR1 induced membrane metalloproteinase-dependent cleavage of vascular endothelial cadherin (VE-cadherin), a principal adhesion molecule that maintains EC junctional integrity. We identified a disintegrin and a metalloproteinase domain 10 (ADAM10) as the principal VE-cadherin "sheddase." Mice expressing a stabilized VE-cadherin construct had decreased extravascular VE-cadherin and vascular leakage in response to S1PR1 blockade, and they were protected from SIA. Importantly, patients with active rheumatoid arthritis had decreased circulating S1P and microvascular expression of S1PR1, suggesting a dysregulated S1P/S1PR1 axis favoring vascular permeability and vulnerability. We present a model in which EC S1PR1 signaling maintains homeostatic vascular barrier function by limiting VE-cadherin shedding mediated by ADAM10 and suggest this signaling axis as a therapeutic target in inflammatory arthritis.
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Proteína ADAM10 , Antígenos CD , Artritis Experimental , Artritis Reumatoide , Cadherinas , Células Endoteliales , Receptores de Esfingosina-1-Fosfato , Animales , Cadherinas/metabolismo , Receptores de Esfingosina-1-Fosfato/metabolismo , Receptores de Esfingosina-1-Fosfato/genética , Ratones , Artritis Experimental/metabolismo , Artritis Experimental/patología , Antígenos CD/metabolismo , Antígenos CD/genética , Células Endoteliales/metabolismo , Humanos , Artritis Reumatoide/metabolismo , Artritis Reumatoide/patología , Artritis Reumatoide/genética , Proteína ADAM10/metabolismo , Proteína ADAM10/genética , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Transducción de Señal , Ratones Noqueados , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Masculino , Esfingosina/análogos & derivados , Esfingosina/metabolismo , Lisofosfolípidos/metabolismo , Permeabilidad Capilar , FemeninoRESUMEN
The cell surface metalloprotease ADAM17 (a disintegrin and metalloprotease 17) and its binding partners iRhom2 and iRhom1 (inactive Rhomboid-like proteins 1 and 2) modulate cell-cell interactions by mediating the release of membrane proteins such as TNFα (Tumor necrosis factor α) and EGFR (Epidermal growth factor receptor) ligands from the cell surface. Most cell types express both iRhoms, though myeloid cells exclusively express iRhom2, and iRhom1 is the main iRhom in the mouse brain. Here, we report that iRhom2 is uniquely expressed in olfactory sensory neurons (OSNs), highly specialized cells expressing one olfactory receptor (OR) from a repertoire of more than a thousand OR genes in mice. iRhom2-/- mice had no evident morphological defects in the olfactory epithelium (OE), yet RNAseq analysis revealed differential expression of a small subset of ORs. Notably, while the majority of ORs remain unaffected in iRhom2-/- OE, OSNs expressing ORs that are enriched in iRhom2-/- OE showed fewer gene expression changes upon odor environmental changes than the majority of OSNs. Moreover, we discovered an inverse correlation between the expression of iRhom2 compared to OSN activity genes and that odor exposure negatively regulates iRhom2 expression. Given that ORs are specialized G-protein coupled receptors (GPCRs) and many GPCRs activate iRhom2/ADAM17, we investigated if ORs could activate iRhom2/ADAM17. Activation of an olfactory receptor that is ectopically expressed in keratinocytes (OR2AT4) by its agonist Sandalore leads to ERK1/2 phosphorylation, likely via an iRhom2/ADAM17-dependent pathway. Taken together, these findings point to a mechanism by which odor stimulation of OSNs activates iRhom2/ADAM17 catalytic activity, resulting in downstream transcriptional changes to the OR repertoire and activity genes, and driving a negative feedback loop to downregulate iRhom2 expression.
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Neuronas Receptoras Olfatorias , Receptores Odorantes , Animales , Receptores Odorantes/metabolismo , Receptores Odorantes/genética , Ratones , Neuronas Receptoras Olfatorias/metabolismo , Olfato/fisiología , Proteína ADAM17/metabolismo , Proteína ADAM17/genética , Ratones Noqueados , Proteínas Portadoras/metabolismo , Proteínas Portadoras/genética , Mucosa Olfatoria/metabolismo , Regulación de la Expresión Génica , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Ratones Endogámicos C57BL , HumanosRESUMEN
Women with antiphospholipid syndrome (APS) are at high risk for miscarriage and preeclampsia. Unlike pro-thrombotic systemic APS, obstetric APS is associated with insufficient placentation, as well as inflammation and vascular dysfunction at the maternal-fetal interface. Antiphospholipid antibodies (aPL) can target the placental trophoblast and induce inflammation. We reported that aPL trigger trophoblast cells to produce elevated levels of IL-8 through activation of Toll-like receptor 4 (TLR4). Downstream of TLR4, we found this IL-8 response is mediated by a TLR8-activating microRNA (miR), miR-146a-3p, which is also released by the trophoblast via extracellular vesicles (EVs). Since endothelial dysfunction is a feature of obstetric APS, we sought to determine if other miRs that can activate the RNA sensors, TLR7 and/or TLR8, are released by the trophoblast via EVs after exposure to aPL, and if these EVs can activate human endometrial endothelial cells (HEECs). Using a human first trimester extravillous trophoblast cell line we found that aPL elevated their release of small EVs (<150â¯nm). These extracellular vesicles released from trophoblast cells exposed to aPL expressed elevated levels of TLR7/8-activating miR-21a and miR-29a, in addition to the previously reported miR-146a-3p. Extracellular vesicles from aPL-exposed human trophoblast cells triggered human endometrial endothelial cells to generate an inflammatory IL-8 response, in part through TLR7. This study highlights EVs as a mode of communication between the placenta and the maternal vasculature, as well as a potential role for TLR7/8-activating miRs in contributing to inflammation at the maternal-fetal interface in obstetric APS.
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Anticuerpos Antifosfolípidos , Síndrome Antifosfolípido , Vesículas Extracelulares , MicroARNs , Receptor Toll-Like 7 , Receptor Toll-Like 8 , Trofoblastos , Humanos , Femenino , Trofoblastos/metabolismo , Trofoblastos/inmunología , MicroARNs/metabolismo , MicroARNs/genética , Receptor Toll-Like 7/metabolismo , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/inmunología , Embarazo , Receptor Toll-Like 8/metabolismo , Receptor Toll-Like 8/inmunología , Síndrome Antifosfolípido/inmunología , Síndrome Antifosfolípido/metabolismo , Anticuerpos Antifosfolípidos/inmunología , Anticuerpos Antifosfolípidos/metabolismo , Endometrio/metabolismo , Endometrio/inmunología , Endometrio/patología , Células Endoteliales/metabolismo , Células Endoteliales/inmunología , Línea Celular , Interleucina-8/metabolismoRESUMEN
OBJECTIVE: Preterm birth is one of the most frequent complications of pregnancy in women with systemic lupus erythematosus. The high indicated preterm birth proportion due to hypertensive disorders of pregnancy and/or fetal growth restriction is well known, and preventive measures and screening for early detection are performed. The risk of spontaneous preterm birth is less well recognized. This study aimed to determine the proportions of spontaneous and indicated preterm birth in pregnancies of women with systemic lupus erythematosus. DATA SOURCES: A systematic literature search using Pubmed, Embase, Web of Science, and Google Scholar was performed in June 2021. STUDY ELIGIBILITY CRITERIA: Studies in pregnant women with systemic lupus erythematosus reporting spontaneous and indicated preterm birth rates were selected. Original research articles published from 1995 to June 2021 were included. METHODS: Quality and risk of bias of the included studies were assessed using the Newcastle-Ottawa quality assessment scale. To estimate the pooled event rates and 95% confidence intervals, meta-analysis of single proportions with a random-effects model was performed. RESULTS: We included 21 articles, containing data of 8157 pregnancies in women with systemic lupus erythematosus. On average, 31% (95% prediction interval, 0.14-0.50) of the pregnancies resulted in preterm birth, including 14% (95% prediction interval, 0.04-0.27) spontaneous and 16% (95% prediction interval, 0.03-0.35) indicated preterm birth. CONCLUSION: In pregnant women with systemic lupus erythematosus, spontaneous and indicated preterm birth proportions are high. This information should be applied in (prepregnancy) counseling and management in pregnancy. The knowledge obtained by this meta-analysis paves the way for further research of associated risk factors and development of interventions to reduce spontaneous preterm birth in systemic lupus erythematosus pregnancies.
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Objective: Leveraging the Manhattan Lupus Surveillance Program (MLSP), a population-based registry of cases of systemic lupus erythematosus (SLE) and related diseases, we investigated the proportion of SLE with concomitant rheumatic diseases, including Sjögren's disease (SjD), antiphospholipid syndrome (APLS), and fibromyalgia (FM), as well as the prevalence of autoantibodies in SLE by sex and race/ethnicity. Methods: Prevalent SLE cases fulfilled one of three sets of classification criteria. Additional rheumatic diseases were defined using modified criteria based on data available in the MLSP: SjD (anti-SSA/Ro positive and evidence of keratoconjunctivitis sicca and/or xerostomia), APLS (antiphospholipid antibody positive and evidence of a blood clot), and FM (diagnosis in the chart). Results: 1,342 patients fulfilled SLE classification criteria. Of these, SjD was identified in 147 (11.0%, 95% CI 9.2-12.7%) patients with women and non-Latino Asian patients being the most highly represented. APLS was diagnosed in 119 (8.9%, 95% CI 7.3-10.5%) patients with the highest frequency in Latino patients. FM was present in 120 (8.9%, 95% CI 7.3-10.5) patients with non-Latino White and Latino patients having the highest frequency. Anti-dsDNA antibodies were most prevalent in non-Latino Asian, Black, and Latino patients while anti-Sm antibodies showed the highest proportion in non-Latino Black and Asian patients. Anti-SSA/Ro and anti-SSB/La antibodies were most prevalent in non-Latino Asian patients and least prevalent in non-Latino White patients. Men were more likely to be anti-Sm positive. Conclusion: Data from the MLSP revealed differences among patients classified as SLE in the prevalence of concomitant rheumatic diseases and autoantibody profiles by sex and race/ethnicity underscoring comorbidities associated with SLE.
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OBJECTIVE: To evaluate and quantify the indicators of fetal and maternal morbidity in deliveries for patients with systemic lupus erythematosus (SLE) compared with deliveries in patients without SLE. METHODS: We used retrospective data from the National Inpatient Sample (NIS) to identify all delivery related hospital admissions of patients with and without SLE from 2008 to 2017 using ICD-9/10 codes. Fetal morbidity indicators included pre-term delivery and intrauterine growth restriction (IUGR). 21 indicators of severe maternal morbidity were identified using standard Centers for Disease Control and Prevention (CDC) definitions. Descriptive statistics, including 95% confidence intervals, were calculated using sample weights from the NIS dataset. RESULTS: Among the 40 million delivery-related admissions, 51 161 patients were reported to have SLE. Patients with SLE had a higher risk of fetal morbidity, including IUGR (8.0% vs 2.7%) and pre-term delivery (14.5% vs 7.3%), than patients without SLE. During delivery, mothers with SLE were nearly four times as likely to require a blood transfusion or develop a cerebrovascular disorder, and 15 times as likely to develop acute renal failure than those without SLE. CONCLUSION: Our study demonstrates that fetal morbidity and severe maternal morbidity occur at a higher rate in patients with SLE compared with those without. This quantitative work can help inform and counsel patients with SLE during pregnancy and planning.
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Lupus Eritematoso Sistémico , Complicaciones del Embarazo , Embarazo , Femenino , Humanos , Resultado del Embarazo , Complicaciones del Embarazo/epidemiología , Estudios Retrospectivos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/epidemiología , HospitalizaciónRESUMEN
OBJECTIVE: The objective of the study was to investigate the role of genetic variants in complement proteins in pre-eclampsia. DESIGN: In a case-control study involving 609 cases and 2092 controls, five rare variants in complement factor H (CFH) were identified in women with severe and complicated pre-eclampsia. No variants were identified in controls. SETTING: Pre-eclampsia is a leading cause of maternal and fetal morbidity and mortality. Immune maladaptation, in particular, complement activation that disrupts maternal-fetal tolerance leading to placental dysfunction and endothelial injury, has been proposed as a pathogenetic mechanism, but this remains unproven. POPULATION: We genotyped 609 pre-eclampsia cases and 2092 controls from FINNPEC and the national FINRISK cohorts. METHODS: Complement-based functional and structural assays were conducted in vitro to define the significance of these five missense variants and each compared with wild type. MAIN OUTCOME MEASURES: Secretion, expression and ability to regulate complement activation were assessed for factor H proteins harbouring the mutations. RESULTS: We identified five heterozygous rare variants in complement factor H (L3V, R127H, R166Q, C1077S and N1176K) in seven women with severe pre-eclampsia. These variants were not identified in controls. Variants C1077S and N1176K were novel. Antigenic, functional and structural analyses established that four (R127H, R166Q, C1077S and N1176K) were deleterious. Variants R127H and C1077S were synthesised, but not secreted. Variants R166Q and N1176K were secreted normally but showed reduced binding to C3b and consequently defective complement regulatory activity. No defect was identified for L3V. CONCLUSIONS: These results suggest that complement dysregulation due to mutations in complement factor H is among the pathophysiological mechanisms underlying severe pre-eclampsia.
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Factor H de Complemento , Preeclampsia , Humanos , Embarazo , Femenino , Factor H de Complemento/genética , Factor H de Complemento/metabolismo , Estudios de Casos y Controles , Placenta/metabolismo , Preeclampsia/genética , GenotipoRESUMEN
OBJECTIVE: Epidemiological data for MCTD are limited. Leveraging data from the Manhattan Lupus Surveillance Program (MLSP), a racially/ethnically diverse population-based registry of cases with SLE and related diseases including MCTD, we provide estimates of the prevalence and incidence of MCTD. METHODS: MLSP cases were identified from rheumatologists, hospitals and population databases using a variety of International Classification of Diseases, Ninth Revision codes. MCTD was defined as one of the following: fulfilment of our modified Alarcon-Segovia and Kahn criteria, which required a positive RNP antibody and the presence of synovitis, myositis and RP; a diagnosis of MCTD and no other diagnosis of another CTD; and a diagnosis of MCTD regardless of another CTD diagnosis. RESULTS: Overall, 258 (7.7%) cases met a definition of MCTD. Using our modified Alarcon-Segovia and Kahn criteria for MCTD, the age-adjusted prevalence was 1.28 (95% CI 0.72, 2.09) per 100 000. Using our definition of a diagnosis of MCTD and no other diagnosis of another CTD yielded an age-adjusted prevalence and incidence of MCTD of 2.98 (95% CI 2.10, 4.11) per 100 000 and 0.39 (95% CI 0.22, 0.64) per 100 000, respectively. The age-adjusted prevalence and incidence were highest using a diagnosis of MCTD regardless of other CTD diagnoses and were 16.22 (95% CI 14.00, 18.43) per 100 000 and 1.90 (95% CI 1.49, 2.39) per 100 000, respectively. CONCLUSIONS: The MLSP provided estimates for the prevalence and incidence of MCTD in a diverse population. The variation in estimates using different case definitions is reflective of the challenge of defining MCTD in epidemiologic studies.
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Lupus Eritematoso Sistémico , Enfermedad Mixta del Tejido Conjuntivo , Miositis , Humanos , Enfermedad Mixta del Tejido Conjuntivo/diagnóstico , Enfermedad Mixta del Tejido Conjuntivo/epidemiología , Prevalencia , Incidencia , Anticuerpos AntinuclearesRESUMEN
OBJECTIVE: Using the Manhattan Lupus Surveillance Program, a multiracial/ethnic population-based registry, we aimed to compare 3 commonly used classification criteria for systemic lupus erythematosus (SLE) to identify unique cases and determine the incidence and prevalence of SLE using the EULAR/American College of Rheumatology (ACR) criteria. METHODS: SLE cases were defined as fulfilling the 1997 ACR, the Systemic Lupus International Collaborating Clinics (SLICC), or the EULAR/ACR classification criteria. We quantified the number of cases uniquely associated with each and the number fulfilling all 3 criteria. Prevalence and incidence using the EULAR/ACR classification criteria and associated 95% confidence intervals (95% CIs) were calculated. RESULTS: A total of 1,497 cases fulfilled at least 1 of the 3 classification criteria, with 1,008 (67.3%) meeting all 3 classifications, 138 (9.2%) fulfilling only the SLICC criteria, 35 (2.3%) fulfilling only the 1997 ACR criteria, and 34 (2.3%) uniquely fulfilling the EULAR/ACR criteria. Patients solely satisfying the EULAR/ACR criteria had <4 manifestations. The majority classified only by the 1997 ACR criteria did not meet any of the defined immunologic criteria. Patients fulfilling only the SLICC criteria did so based on the presence of features unique to this system. Using the EULAR/ACR classification criteria, age-adjusted overall prevalence and incidence rates of SLE in Manhattan were 59.6 (95% CI 55.9-63.4) and 4.9 (95% CI 4.3-5.5) per 100,000 population, with age-adjusted prevalence and incidence rates highest among non-Hispanic Black female patients. CONCLUSION: Applying the 3 commonly used classification criteria to a population-based registry identified patients with SLE fulfilling only 1 validated definition. The most recently developed EULAR/ACR classification criteria revealed prevalence and incidence estimates similar to those previously established for the ACR and SLICC classification schemes.
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Lupus Eritematoso Sistémico , Reumatología , Humanos , Femenino , Estados Unidos , Lupus Eritematoso Sistémico/epidemiología , Incidencia , Prevalencia , Sistema de RegistrosAsunto(s)
Síndrome de Sjögren , Femenino , Humanos , Embarazo , Pacientes , Síndrome de Sjögren/diagnóstico , Estudios ProspectivosAsunto(s)
Lupus Eritematoso Sistémico , Linfocitos T , Linfocitos B , Humanos , Recuento de LinfocitosRESUMEN
Sphingosine 1-phosphate (S1P), which acts via G protein-coupled S1P receptors (S1PRs), is a bioactive lipid essential for vascular integrity and lymphocyte trafficking. The S1P-S1PR signalling axis is a key component of the inflammatory response in autoimmune rheumatic diseases. Several drugs that target S1PRs have been approved for the treatment of multiple sclerosis and inflammatory bowel disease and are under clinical testing for patients with systemic lupus erythematosus (SLE). Preclinical studies support the hypothesis that targeting the S1P-S1PR axis would be beneficial to patients with SLE, rheumatoid arthritis (RA) and systemic sclerosis (SSc) by reducing pathological inflammation. Whereas most preclinical research and development efforts are focused on reducing lymphocyte trafficking, protective effects of circulating S1P on endothelial S1PRs, which maintain the vascular barrier and enable blood circulation while dampening leukocyte extravasation, have been largely overlooked. In this Review, we take a holistic view of S1P-S1PR signalling in lymphocyte and vascular pathobiology. We focus on the potential of S1PR modulators for the treatment of SLE, RA and SSc and summarize the rationale, pathobiology and evidence from preclinical models and clinical studies. Improved understanding of S1P pathobiology in autoimmune rheumatic diseases and S1PR therapeutic modulation is anticipated to lead to efficacious and safer management of these diseases.
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Lupus Eritematoso Sistémico , Esclerosis Múltiple , Enfermedades Reumáticas , Humanos , Esclerosis Múltiple/tratamiento farmacológico , Receptores de Lisoesfingolípidos/uso terapéutico , Enfermedades Reumáticas/tratamiento farmacológico , Transducción de Señal , Receptores de Esfingosina-1-FosfatoRESUMEN
OBJECTIVE: Miscarriage affects 1 in 7 pregnancies, and antiphospholipid autoantibodies (aPLs) are one of the biggest risk factors for recurrent pregnancy loss. While aPLs target the endometrial stroma, little is known about their impact. Endometrial stromal cells (EnSCs) undergo decidualization each menstrual cycle, priming the uterus to receive implanting embryos. Thus, appropriate decidualization and EnSC function is key for establishment of a successful pregnancy. This study was undertaken to explore the effects of aPL on EnSC decidualization, senescence, and inflammation. METHODS: EnSCs under decidualizing conditions were exposed to aPL or control IgG alone or in the presence of either a Toll-like receptor 4 (TLR-4) antagonist, a p38 MAPK inhibitor, a reactive oxygen species (ROS) inhibitor, low molecular weight heparin (LMWH), or acetyl salicylic acid. Secretion of decidualization markers and inflammatory interleukin-8 were quantified by enzyme-linked immunosorbent assay, and senescence-associated ß-galactosidase activity was evaluated. In a mouse model of decidualization, aPL or control IgG was administered, and uterine expression levels of decidualization and inflammatory markers were quantified by real-time quantitative polymerase chain reaction. RESULTS: Antiphospholipid antibodies increased human EnSC decidualization, senescence, and inflammation. This phenotype was recapitulated in the mouse model. The decidualization and inflammatory responses were partially mediated by TLR-4 and p38 MAPK, while the decidualization and senescence responses were ROS-dependent. LMWH, commonly used to treat aPL-positive women at risk of obstetric complications, reduced the ability of aPL to increase EnSC decidualization and inflammation. CONCLUSION: These findings shed new light on the pathogenesis of pregnancy complications in women with aPLs and underscore the benefit of heparin in preventing pregnancy loss in this high-risk population.
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Anticuerpos Antifosfolípidos , Sistema de Señalización de MAP Quinasas , Especies Reactivas de Oxígeno , Células del Estroma , Receptor Toll-Like 4 , Proteínas Quinasas p38 Activadas por Mitógenos , Animales , Anticuerpos Antifosfolípidos/metabolismo , Endometrio/metabolismo , Femenino , Heparina de Bajo-Peso-Molecular/farmacología , Inmunoglobulina G/metabolismo , Inflamación/metabolismo , Ratones , Embarazo , Especies Reactivas de Oxígeno/metabolismo , Células del Estroma/metabolismo , Receptor Toll-Like 4/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
[Figure: see text].
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Síndrome Antifosfolípido/metabolismo , Proteínas Relacionadas con Receptor de LDL/metabolismo , Preeclampsia/metabolismo , Proteína Fosfatasa 2/metabolismo , Trofoblastos/metabolismo , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Animales , Anticuerpos Antifosfolípidos/sangre , Síndrome Antifosfolípido/complicaciones , Proteínas Reguladoras de la Apoptosis/metabolismo , Línea Celular , Femenino , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Ratones , Ratones Endogámicos C57BL , Preeclampsia/etiología , EmbarazoRESUMEN
OBJECTIVE: The aim of this study was to evaluate the initial impact of the COVID-19 pandemic on individuals with systemic lupus erythematosus (SLE). METHODS: Patients with SLE participating in a multi-center longitudinal cohort study in New York and Boston were invited to complete a supplemental web-based questionnaire in the summer of 2020. Participants completed standardized patient-reported outcome (PRO) measures and a combination of Likert scale and open-ended questions exploring the impact of the COVID-19 pandemic on their health and access to health care. Changes in PROs were evaluated with paired t-tests and frequencies of worsened symptoms were calculated. A thematic qualitative analysis was conducted on free text responses. RESULTS: Of 97 patients invited, 63 (65%) completed a supplemental questionnaire. Nearly 50% of respondents exhibited increases in anxiety (47.5%) and depression (48.3%) and over 40% scored worse in measures of pain interference, fatigue, and cognitive abilities. Respondents with pre-existing diagnoses of anxiety did not differ from other participants in PRO scores, but were more than three times as likely to report worsened health status. Patients denied difficulties accessing medications (85%) or medical care (84%) and over 50% participated in telehealth visits. Anxiety and increased health risks due to immunosuppression were recurring themes in free text responses. CONCLUSIONS: SLE patients experienced a significant physical and emotional toll in the initial months of the COVID-19 pandemic. Comprehensive patient-centered care, including monitoring and addressing anxiety and health-related quality of life, is critical to improving health outcomes in this population during the ongoing health crisis.
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Ansiedad/psicología , Depresión/psicología , Lupus Eritematoso Sistémico/psicología , Dolor/psicología , Calidad de Vida , Adulto , Anciano , COVID-19/epidemiología , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Pandemias , Medición de Resultados Informados por el Paciente , Estudios Prospectivos , SARS-CoV-2 , Telemedicina/estadística & datos numéricosRESUMEN
OBJECTIVE: Hypertensive disorders of pregnancy (HDPs) increase cardiovascular disease (CVD) risk. Pregnancy morbidities, including preeclampsia and CVD, are common in systemic lupus erythematosus (SLE). Possible connections are important to explore. In a population-based cohort, we investigated whether HDPs are associated with a higher risk of cardiovascular outcomes separately in women with SLE and those without SLE to examine the role of SLE. METHODS: We identified first singleton births in the Medical Birth Register (1987-2012) among mothers with SLE and a large general population comparison group. Discharge diagnoses for HDPs, cardiovascular outcomes, and hypertension in the National Patient Register were identified using International Classification of Diseases codes. We estimated adjusted hazard ratios and 95% confidence intervals of the association between HDPs and outcomes in separate models in women with and without SLE. We then evaluated additive and multiplicative effect modification using relative excess risk due to interaction and Cox models jointly accounting for SLE and HDPs, respectively. Mediation analysis estimated the proportion of the association between SLE and outcome explained by HDPs. RESULTS: HDPs were more common in pregnant women with SLE (20% versus 7%). In SLE, HDPs were associated with a 2-fold higher rate of cardiovascular outcomes and a 3-fold higher rate of incident hypertension. HDPs mediated 20% of the latter association. In women without SLE, HDPs were associated with higher incidence of hypertension later in life. CONCLUSION: In women with SLE and those without SLE, HDPs were associated with a 3-fold higher rate of hypertension. In SLE, women with HDPs developed cardiovascular outcomes twice as often as women without HDPs.
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Enfermedades Cardiovasculares/epidemiología , Hipertensión Inducida en el Embarazo/epidemiología , Lupus Eritematoso Sistémico/epidemiología , Adulto , Enfermedades Cardiovasculares/diagnóstico , Femenino , Humanos , Hipertensión Inducida en el Embarazo/diagnóstico , Incidencia , Estudios Longitudinales , Lupus Eritematoso Sistémico/diagnóstico , Embarazo , Prevalencia , Pronóstico , Sistema de Registros , Medición de Riesgo , Factores de Riesgo , Suecia/epidemiologíaRESUMEN
OBJECTIVE: The present study was undertaken to evaluate the pregnancy experiences of women receiving care in the division of rheumatology at a major academic center in New York City during the COVID-19 pandemic. METHODS: A web-based COVID-19 survey was emailed to 26,045 patients who were followed in the division of rheumatology at a single center in New York City. Women ages 18-50 years were asked about their pregnancy. We compared the COVID-19 experience between pregnant and nonpregnant women and also explored the impact of the pandemic on prenatal care and perinatal outcomes. RESULTS: Among 7,094 of the 26,045 respondents, 1,547 were women ages 18-50 years, with 61 (4%) reporting being pregnant during the pandemic. The prevalence of self-reported COVID-19 was similar in pregnant and nonpregnant women (8% versus 9%, respectively; P = 0.76). Among women with COVID-19, pregnant women had a shorter duration of symptoms (P < 0.01) and were more likely to experience loss of smell or taste (P = 0.02) than nonpregnant women. Approximately three-fourths of women had a systemic rheumatic disease, with no differences when stratified by pregnancy or COVID-19 status. In all, 67% of pregnant women noted changes to prenatal care during the pandemic, and 23% of postpartum women stated that the pandemic affected delivery. CONCLUSION: Among women followed in the division of rheumatology at a major center in New York City, pregnancy was not associated with increased self-reported COVID-19. Pregnancy was associated with a shorter duration of COVID-19 symptoms and a higher prevalence of loss of smell or taste. The COVID-19 pandemic impacted prenatal care for the majority of pregnant patients.