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Ricard Cervera

Publications and source records attributed to Ricard Cervera.

At least 19 recordsLinked to original sources
PubMed2025

A proteomic map of thromboinflammatory signatures in antiphospholipid syndrome: results from antiphospholipid syndrome alliance for clinical trials and international networking (APS ACTION) registry.

INTRODUCTION: Antiphospholipid syndrome (APS) is an autoimmune disease with thromboembolic and obstetric morbidity arising via a model of immunothrombosis. Individuals with APS may present with thrombotic (TAPS), obstetric (OAPS), or microvascular (MAPS) disease, while many have circulating antiphospholipid antibodies (aPL) without APS classification (NoAPS). Multiple pathophysiologic mechanisms have been proposed in APS, including activation by aPL of platelets, endothelial and immune cells, as well as complement and coagulation pathways; however, the pathophysiology of APS, particularly transition of clinical APS from aPL remains unclear. METHODS: Seeking to define the inflammatory signature of APS, we carried out an unbiased proteomic screen of persistently aPL-positive patients with different clinical phenotypes from the international APS Alliance for Clinical Trials and International Networking (ACTION) Registry and compared them to 10 healthy controls. 6398 unique proteins were estimated using an DNA aptamer-based assay. Subsequently, we validated our findings in 34 additional patients. RESULTS: Our data show that the mere presence of aPL confers a distinct thromboinflammatory signature characterized by the activation of coagulation, complement, innate and adaptive immune response pathways shared by all APS subtypes. Pathway enrichment analysis revealed increasing enrichment with rising statistical significance of thrombosis, complement, neutrophil and other innate and adaptive immune activation, as well as extracellular matrix (ECM) organization with increasing clinical severity, suggesting a model of progressive thromboinflammation in evolution of APS from NoAPS to TAPS and MAPS. CONCLUSIONS: Our findings provide novel insights into the pathogenesis of APS and identify potential novel targets for diagnostic and therapeutic intervention in APS across its entire spectrum.

Humans↗
PubMed2007

Catastrophic antiphospholipid syndrome during pregnancy and puerperium: maternal and fetal characteristics of 15 cases.

BACKGROUND: The catastrophic variant of the antiphospholipid syndrome (APS) is a life-threatening form of presentation of this syndrome that can be triggered by several factors. AIM: To describe the characteristics of patients who developed catastrophic APS triggered during pregnancy and puerperium. METHODS: A review of the first 255 cases collected in the website-based "CAPS Registry" was undertaken. Three new and unpublished cases of catastrophic APS developed during pregnancy and puerperium were added. RESULTS: Fifteen cases were identified. The mean (range) age was 27 (17-38) years. Most patients had a previous unsuccessful obstetric history. In 7 of 14 (50%) cases with available medical history, the catastrophic APS appeared during pregnancy, in 6 (43%) during the puerperium and in 1 (7%) after curettage for a fetal death. The main clinical and serological characteristics were similar to those patients with catastrophic APS triggered by other factors, except for a history of a higher prevalence of previous abortions (p<0.01). Several specific features were found, including the HELLP (haemolysis, elevated liver enzymes, low platelets) syndrome in 8 (53%) patients, placental infarctions in 4 (27%) patients, and pelvic vein thrombosis and myometrium thrombotic microangiopathy in 1 (7%) patient each. Mortality rate was high for the mothers (46%), and for the babies (54%). CONCLUSIONS: It is important to consider the possibility of the development of catastrophic APS in those patients with signs of HELLP syndrome and multiorgan failure during pregnancy or puerperium, especially in those patients with previous history of abortions and/or thrombosis.

Adolescent↗
PubMed2007

Intestinal involvement secondary to the antiphospholipid syndrome (APS): clinical and immunologic characteristics of 97 patients: comparison of classic and catastrophic APS.

OBJECTIVE: To analyze the clinical and laboratory characteristics of 97 patients with intestinal involvement secondary to the antiphospholipid syndrome (APS) (37 patients with classic APS and 60 with catastrophic APS). METHODS: A computer-assisted (PubMed) search of the literature was performed to identify all cases of intestinal involvement associated with the APS from 1983 to December 2005. In addition, we analyzed the web-site-based international registry of patients with catastrophic APS ("CAPS Registry"). RESULTS: There were no differences in distribution by gender, mean age, and previous clinical manifestations of APS between the 2 groups. The prevalence of abdominal pain as the presenting manifestation of intestinal ischemia was higher in patients with classic APS (76% versus 37%; P < 0.005). The main difference in histopathologic findings between the 2 groups was the higher rate of microthrombosis in patients with catastrophic APS (75% versus 4%; P < 0.0005). The mortality rate was higher in patients with catastrophic APS (55% versus 17%; P < 0.0005). Follow-up was available in 22 patients with classical APS: 17 of them were discharged on oral anticoagulation and with a mean follow-up of 13 months (range, 1 to 48); all were in good health without the development of new thrombotic events. CONCLUSIONS: Intestinal involvement, although infrequent, is an important complication in patients with APS, especially in those with catastrophic APS. This would support the need for systematic screening for aPL in all cases of mesenteric thrombosis or ischemic colitis without clear underlying predisposing factors, and for systematic screening procedures in all classic APS patients complaining of abdominal pain.

Adolescent↗
PubMed2006

Insulin resistance, chronic inflammatory state and the link with systemic lupus erythematosus-related coronary disease.

The association of SLE with atherosclerosis suggests a common pathogenic mechanism. SLE and atherosclerosis are immune complex-mediated diseases. The integration of metabolism and immunity, which under normal conditions is beneficial for the maintenance of good health, can become deteriorative under conditions of metabolic challenge, as exemplified by the immunosuppression characteristic of malnourished or starving individuals. It is now apparent that obesity is associated with a state of chronic inflammation, particularly in white adipose tissue. However, in the absence of obesity, infusion of animals with inflammatory cytokines or lipids can cause insulin resistance. It is possible that the stresses of obesity are similar enough to the stresses of an infection and the body reacts to obesity as it would to an infection. Atherosclerosis can be considered to have a significant chronic inflammatory component. Inflammation also contributes to the typical dyslipidemia associated with SLE that is characterized by elevations of VLDL, LDL and triglycerides as well as reduced HDL. The link between insulin resistance and SLE can be explained by the chronic inflammatory state, and the consequent dyslipoproteinemia.

Chronic Disease↗
PubMed2006

Mortality in the catastrophic antiphospholipid syndrome: causes of death and prognostic factors.

In order to know the causes of death and the prognostic factors, our group analyzed 250 patients included until February 2005 in the web-site based international registry of patients with catastrophic antiphospholipid syndrome (APS) ("CAPS Registry") (http://www.med.ub.es/MIMMUN/FORUM/CAPS.HTM). Cerebral involvement, mainly consisting of stroke, followed by cardiac involvement and infections were considered the main causes of death in patients with catastrophic APS. The presence of systemic lupus erythematosus was related with higher mortality. According to the results of this analysis, anticoagulation plus steroids plus plasma exchange should be the first line of therapy in patients with catastrophic APS.

Age of Onset↗
PubMed2006

Lessons from the catastrophic antiphospholipid syndrome (CAPS) registry.

Although less than 1% of patients with the antiphospholipid syndrome (APS) develop the catastrophic variant, its potentially lethal outcome emphasizes its importance in clinical medicine today. However, the rarity of this variant makes it extraordinarily difficult to study in any systematic way. In order to put together all the published case reports as well as the new diagnosed cases from all over the world, an international registry of patients with catastrophic APS ("CAPS Registry") was created in 2000 by the European Forum on Antiphospholipid Antibodies. Currently, it documents the entire clinical, laboratory and therapeutic data of more than 300 patients whose data has been fully registered. This registry can be freely consulted at the Internet (www.med.ub.es/MIMMUN/FORUM/CAPS.HTM) and it is expected that the periodical analysis of these data will allow us to increase our knowledge of this condition.

Antiphospholipid Syndrome↗
PubMed2006

Pregnancy and puerperium are high susceptibility periods for the development of catastrophic antiphospholipid syndrome.

It is well known that antiphospholipid syndrome (APS) is associated with recurrent pregnancies losses, but is also associated with other obstetric features such as preeclampsia, uteroplacental insufficiency and preterm birth. Pregnancy is a hypercoagulable state than can be complicated by thrombosis, especially in those patients with an underlying thrombophilic disorder. Catastrophic APS is a rare form of presentation of the APS. Several trigger factors have been related with the catastrophic APS, including infections, anticoagulation withdrawal, surgery, neoplasms and lupus "flares". In around 6% of the cases, the catastrophic APS can appear during pregnancy or puerperium. We review this specific subset of the catastrophic APS and propose a therapeutical approach for this particular situation.

Antiphospholipid Syndrome↗
PubMed2006

Laboratory studies on pathophysiology of the catastrophic antiphospholipid syndrome.

The 'catastrophic' variant of the antiphospholipid syndrome (APS) is characterized by a diffuse thrombotic microvasculopathy. In contrast to the classical APS, single venous or arterial medium-to-large blood vessel occlusions are uncommon. The mechanisms of catastrophic APS are not clearly understood. In addition, there are no studies on pathophysiologic mechanisms of catastrophic APS. The clinical manifestations of catastrophic APS probably depend on (a) the organs affected by the thrombotic events and extent of the thrombosis and (b) manifestations of the systemic inflammatory response syndrome which are presumed to be due to excessive cytokine release from affected and necrotic tissues. The evident relationship between APS and infection may enable us to explain the development of catastrophic APS using the sepsis model. This is because catastrophic APS is characterized by multiple microvascular thrombotic events, of rapid onset, and causing multiorgan failure, a picture suggestive of septic shock, in which, there is a massive, acute inflammatory response.

Antiphospholipid Syndrome↗
PubMed2006

European Working Party on Systemic Lupus Erythematosus: a 15-year report.

The "European Working Party on Systemic Lupus Erythematosus" was created 15 years ago in order to promote research in Europe on the different problems related to this disease. Nowadays, more than 50 European centres are collaborating in this venture, 9 large multicentre studies are ongoing and 10 workshops have been organized.

Europe↗
PubMed2006

Anti-inflammatory and immunosuppressive drugs and reproduction.

Rheumatic diseases in women of childbearing years may necessitate drug treatment during a pregnancy, to control maternal disease activity and to ensure a successful pregnancy outcome. This survey is based on a consensus workshop of international experts discussing effects of anti-inflammatory, immunosuppressive and biological drugs during pregnancy and lactation. In addition, effects of these drugs on male and female fertility and possible long-term effects on infants exposed to drugs antenatally are discussed where data were available. Recommendations for drug treatment during pregnancy and lactation are given.

Adult↗
PubMed2006

V meeting of the European forum on antiphospholipid antibodies.

The "V Meeting of the European Forum on Antiphospholipid Antibodies" was organized in Barcelona, Catalonia, Spain, on December 2-3, 2005. This biannual meeting becomes a real forum for the interchange of information on current research on the field antiphospholipid antibodies and the antiphospholipid syndrome, as well as a starting point for many new research projects. About 170 physicians and researchers from a great variety of medical specialities (internists, rheumatologists, hematologists, obstetricians, pediatricians, neurologists, cardiologists, immunologists, and biologists, among others) coming from 20 European countries attended the sessions. This report summarizes the main studies and new research projects presented during this Forum Meeting.

Animals↗
PubMed2006

Mortality in the catastrophic antiphospholipid syndrome: causes of death and prognostic factors in a series of 250 patients.

OBJECTIVE: To assess the main causes of death and the prognostic factors that influence mortality in patients with the catastrophic antiphospholipid syndrome (CAPS). METHODS: We analyzed the case reports of 250 patients included in the CAPS Registry up to February 2005. To identify prognostic factors for CAPS, we compared the main clinical and immunologic features and the types of treatment in the patients who died with those features in the patients who survived. RESULTS: Recovery occurred in 56% of the episodes of CAPS and death occurred in 44%. Cerebral involvement, consisting mainly of stroke, cerebral hemorrhage, and encephalopathy, was considered the main cause of death, being present in 27.2% of patients, followed by cardiac involvement (19.8%) and infection (19.8%). The only factor we identified that was prognostic of a higher mortality rate was the presence of systemic lupus erythematosus (SLE). A higher recovery rate was associated with combined treatment with anticoagulants (ACs) plus corticosteroids (CS) plus plasma exchange (PE) (77.8%), followed by ACs plus CS plus PE and/or intravenous immunoglobulins (69%). In contrast, concomitant treatment with cyclophosphamide did not demonstrate additional benefit. CONCLUSION: Cerebral involvement (mainly consisting of stroke), cardiac involvement, and infections were considered the main causes of death in patients with CAPS. The presence of SLE was related to a higher mortality rate. According to the results of the present study, ACs plus CS plus PE should be the first line of therapy in patients with CAPS.

Adult↗
PubMed2006

Impaired factor XIIa-dependent activation of fibrinolysis in treated antiphospholipid syndrome gestations developing late-pregnancy complications.

OBJECTIVE: The objective of the study was to investigate the potential role of impaired factor XII-dependent activation of fibrinolysis in treated antiphospholipid syndrome gestations developing late-pregnancy complications. STUDY DESIGN: This was a prospective study in a third-level teaching hospital, including 75 patients: 25 pregnant patients having the antiphospholipid syndrome and carrying their pregnancies until 26 weeks' gestation or later (group 1); 25 pregnant patients having normal term pregnancies and delivery and no previous miscarriage (group 2); and 25 pregnant patients being diagnosed as having severe pre-eclampsia and/or intrauterine growth restriction but testing negative for antiphospholipid antibodies (group 3). Hemostatic evaluation was carried out from patients in groups 1 and 2 between 6 and 10 weeks, between 18 and 22 weeks, and between 28 and 32 weeks' gestation. Patients in group 3 were sampled between 28 and 32 weeks. An additional blood sample was obtained 4 to 6 months after delivery (baseline). The Mann-Whitney U test, the Friedman test, and the chi2 test were used. RESULTS: Patients in group 1 were characterized by increased factor VIIa levels, increased prothrombin fragment 1+2 levels, reduced factor XIIa levels, diminished functional urokinase-type plasminogen activator levels, and decreased levels of plasmin/alpha-2-plasmin inhibitor complexes. These abnormalities were more evident in patients in group 1 developing pre-eclampsia and/or intrauterine growth restriction. CONCLUSIONS: Impaired factor XIIa-dependent activation of fibrinolysis seems to be a key mechanism related to late-pregnancy complications in patients with the antiphospholipid syndrome.

Adult↗
PubMed2006

Pathophysiology of Sjögren's syndrome.

The term Sjögren's syndrome refers to keratoconjunctivitis sicca and xerostomia due to lymphocytic infiltrates of lachrymal and salivary glands. The current used criteria for diagnosis of primary Sjögren's syndrome is the American-European consensus. Primary Sjögren's syndrome is an autoimmune disorder characterized by lymphocytic infiltrates and destruction of the salivary and lachrymal glands and systemic production of autoantibodies to the ribonucleoprotein particles SS-A/Ro and SS-B/La. The infiltrating cells (T- and B-cells, dendritic cells) interfere with glandular function at several points: destruction of glandular elements by cell-mediated mechanisms; secretion of cytokines that activate pathways bearing the signature of type 1 and 2 interferons; production of autoantibodies that interfere with muscarinic receptors; and secretion of metalloproteinases (MMPs) that interfere with the interaction of the glandular cell with its extracellular matrix, which is necessary for efficient glandular function. As the process progresses, the mucosal surfaces become sites of chronic inflammation and the start of a vicious circle. Despite extensive study of the underlying cause of Sjögren's syndrome, the pathogenesis remains obscure. In broad terms, pathogenesis is multifactorial; environmental factors are thought to trigger inflammation in individuals with a genetic predisposition to the disorder.

Biomarkers↗
PubMed2006

Catastrophic antiphospholipid syndrome.

Catastrophic APS is a potentially life-threatening condition with a high mortality, which requires high clinical awareness. New mechanisms for its production can only be explored if samples are obtained, stored, and dis-patched to investigation sites in Europe (Barcelona), the United States (Atlanta), and Japan (Sapporo). Details will be posted and made available on the International Registry Web Site in 2006. It is essential that the condition be diagnosed early and treated aggressively. The combination of high doses of iv heparin, iv steroids plus repeated doses of iv gammaglobulins or plasma exchange is the treatment of choice in patients with this severe condition. Additionally, preventive measures in patients with APS may be effective if the development of the catastrophic APS is to be avoided.

Anticoagulants↗
PubMed2006

Antiphospholipid antibodies associated with malignancies: clinical and pathological characteristics of 120 patients.

OBJECTIVE: To describe the different types of malignancies associated with antiphospholipid antibodies (aPL). METHODS: We performed a computer-assisted (MEDLINE, National Library of Medicine, Bethesda, MD) search of the literature from 1966 to 2003 to identify all cases of malignancies having aPL. RESULTS: One hundred twenty patients were found. The mean age was 56+/-17 years (range 5 to 88). Sixty-two (52%) patients were men and 58 (48%) were women. A heterogeneous group of malignancies were found. Regarding hematological malignancies, 10 (8%) patients suffered from B-cell lymphoma, 8 (7%) from spleen lymphoma, 7 (6%) from chronic myeloid leukemia, and 6 (5%) from non-Hodgkin's lymphoma (NHL). Regarding solid tumors, renal cell carcinoma was diagnosed in 7 (6%) patients, primary tumor with unknown origin in 7 (6%), lung adenocarcinoma in 6 (5%), breast carcinoma in 6 (5%), and melanoma in 6 (5%). The main aPL-related manifestations were thrombocytopenia (25%), cerebrovascular accidents (24%), deep vein thrombosis (19%), pulmonary embolism (15%), and heart valve lesions (9%). In 17 cases, catastrophic antiphospholipid syndrome was considered to be triggered by the malignancy. Seventy-one (63%) of 113 patients recovered or are still alive after cancer treatment. Twenty-three (35%) of 65 patients achieved aPL remission after proper treatment of the malignancy. CONCLUSIONS: It is important to bear in mind, especially in elderly patients, that thrombotic events associated with aPL can be the first manifestation of malignancy. At the same time, the presence of aPL in patients with malignancies has important implications in their treatment and prognosis.

Antibodies, Antiphospholipid↗
PubMed2006

Vasculitis in systemic lupus erythematosus: prevalence and clinical characteristics in 670 patients.

We conducted the current study to determine the prevalence and clinical characteristics of vasculitis in a large series of patients with systemic lupus erythematosus (SLE), focusing on the classification and clinical significance of the different types of vasculitis. We studied 670 consecutive patients who fulfilled 4 or more of the 1997 revised criteria for SLE. Definite vasculitis was diagnosed histologically and/or by arteriography, and probable vasculitis was diagnosed clinically when there were characteristic cutaneous lesions. Vasculitides were categorized according to the definitions adopted by the Chapel Hill Consensus Conference. Seventy-six (11%) patients with SLE had vasculitis (68 female patients and 8 male; mean age, 37.8 yr); only 32 (42%) fulfilled the Chapel Hill definitions. Cutaneous lesions were the main clinical presentation of vasculitis, present in 68 (89%) patients, while the remaining 8 (11%) had isolated visceral vasculitis. Compared with SLE patients without vasculitis, patients with vasculitis had a higher prevalence of livedo reticularis (22% vs. 3%; p = 0.028); a higher mean European Consensus Lupus Activity Measurement (ECLAM) score (5.86 vs. 3.87; p < 0.001); and a higher frequency of anemia (62% vs. 17%; p < 0.001), erythrocyte sedimentation rate (ESR) >50 mm/h (60% vs. 15%; p < 0.001), and anti-La/SS-B antibodies (19% vs. 5%; p = 0.014) in the multivariate analysis. With respect to the size of the vessels involved, 65 (86%) patients had small vessel vasculitis (SVV) and 11 (14%) had medium-sized vessel vasculitis (MVV). SLE patients with MVV had a higher prevalence of mononeuritis multiplex (54% vs. 2%; p < 0.001), visceral vasculitis (100% vs. 5%; p < 0.001), and ulcerated/ischemic cutaneous lesions (36% vs. 11%; p = 0.047) and a higher percentage of surgical interventions (45% vs. 0%; p < 0.001) compared with patients with SVV. In conclusion, we observed a heterogeneous presentation of vasculitides arising in the setting of SLE, with nearly 60% of cases not fulfilling the names and definitions adopted by the Chapel Hill Consensus Conference. SVV was the most frequent vasculitis, overwhelmingly cutaneous and clearly differentiated from MVV, which was less frequent but had predominantly visceral involvement (especially of the peripheral nerves). The presence of vasculitis in our patients with SLE was associated with a higher ECLAM score, livedo reticularis, hematologic parameters (anemia, high ESR), and anti-La/SS-B antibodies.

Adolescent↗