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Ricard Cervera

Publications and source records attributed to Ricard Cervera.

70 records · Page 4Linked to original sources
PubMed2002

Immunosuppressive therapy in lupus nephritis: the Euro-Lupus Nephritis Trial, a randomized trial of low-dose versus high-dose intravenous cyclophosphamide.

OBJECTIVE: Glomerulonephritis is a severe manifestation of systemic lupus erythematosus (SLE) that is usually treated with an extended course of intravenous (IV) cyclophosphamide (CYC). Given the side effects of this regimen, we evaluated the efficacy and the toxicity of a course of low-dose IV CYC prescribed as a remission-inducing treatment, followed by azathioprine (AZA) as a remission-maintaining treatment. METHODS: In this multicenter, prospective clinical trial (the Euro-Lupus Nephritis Trial [ELNT]), we randomly assigned 90 SLE patients with proliferative glomerulonephritis to a high-dose IV CYC regimen (6 monthly pulses and 2 quarterly pulses; doses increased according to the white blood cell count nadir) or a low-dose IV CYC regimen (6 fortnightly pulses at a fixed dose of 500 mg), each of which was followed by AZA. Intent-to-treat analyses were performed. RESULTS: Followup continued for a median of 41.3 months in the low-dose group and 41 months in the high-dose group. Sixteen percent of those in the low-dose group and 20% of those in the high-dose group experienced treatment failure (not statistically significant by Kaplan-Meier analysis). Levels of serum creatinine, albumin, C3, 24-hour urinary protein, and the disease activity scores significantly improved in both groups during the first year of followup. Renal remission was achieved in 71% of the low-dose group and 54% of the high-dose group (not statistically significant). Renal flares were noted in 27% of the low-dose group and 29% of the high-dose group. Although episodes of severe infection were more than twice as frequent in the high-dose group, the difference was not statistically significant. CONCLUSION: The data from the ELNT indicate that in European SLE patients with proliferative lupus nephritis, a remission-inducing regimen of low-dose IV CYC (cumulative dose 3 gm) followed by AZA achieves clinical results comparable to those obtained with a high-dose regimen.

Adolescent↗
PubMed2002

Effects of beta2-glycoprotein I and monoclonal anticardiolipin antibodies in platelet interaction with subendothelium under flow conditions.

OBJECTIVE: To evaluate whether the effect of human monoclonal anticardiolipin antibodies (aCL) on platelet interaction with the subendothelium under flow conditions is dependent on beta(2)-glycoprotein I (beta(2)GPI). METHODS: Three monoclonal IgM aCL with anti-beta(2)GPI activity (TM1B3, GR1D5, and EY2C9) obtained from patients with antiphospholipid syndrome, a monoclonal aCL with lupus anticoagulant activity but without anti-beta(2)GPI activity (FRO) obtained from a patient with a splenic lymphoma, and a control monoclonal IgM without aCL activity were used. TM1B3, GR1D5, EY2C9, FRO, and control IgM (30 microg/ml) were added to reconstituted blood containing gel-filtered platelets (200 x 10(9)/liter), factor VIII (100 units/dl), and fibrinogen (1.5 gm/liter). Samples were perfused (wall-shear rate 800 seconds(-1)), with and without the addition of purified beta(2)GPI (20 microg/ml), through annular chambers containing collagen-rich denuded vascular segments, and the percentages of surface covered by platelets and by thrombi were evaluated. RESULTS: No differences in the percentages of surface covered by platelets and by thrombi were observed among samples with TM1B3, GR1D5, EY2C9, FRO, and control IgM added when reconstituted blood samples without beta(2)GPI were used. However, a significant increase in the percentage of surface covered by platelets was observed in the presence of TM1B3, GR1D5, and EY2C9 but not in the presence of FRO when samples containing beta(2)GPI were used. Increased thrombi formation was induced by TM1B3 and GR1D5 but not by EY2C9 or FRO in samples with added beta(2)GPI. CONCLUSION: Monoclonal aCL require anti-beta(2)GPI activity to promote platelet interaction with the subendothelium under flow conditions.

Antibodies, Anticardiolipin↗
PubMed2002

Vascular involvement in Behçet's disease: relation with thrombophilic factors, coagulation activation, and thrombomodulin.

PURPOSE: Thrombosis, usually venous, occurs in 10% to 25% of patients with Behçet's disease, but its pathogenesis is poorly understood. We evaluated parameters of hemostasis and their relation with thrombosis in a series of patients with Behçet's disease. SUBJECTS AND METHODS: We studied 38 patients with Behçet's disease (13 with venous thrombosis), 38 patients with venous thrombosis without thrombophilia, and 100 control subjects. Levels or presence of protein C, protein S, antithrombin, methylenetetrahydrofolate reductase C677T, factor V Leiden, prothrombin gene G20210A, antiphospholipid antibodies, plasminogen, tissue-type plasminogen activator (tPA), type-1 tPA inhibitor (PAI-1), PAI-1 4G/5G polymorphism, prothrombin fragment 1+2, plasmin/alpha(2)-antiplasmin complexes, thrombomodulin, and activated factors VII and XII were determined. RESULTS: There were no deficiencies in protein C, protein S, antithrombin, or factor V Leiden in the patients with Behçet's disease, nor was there evidence of most other thrombotic abnormalities. Compared with control subjects, however, the Behçet's disease group had elevated mean (+/- SD) levels of prothrombin fragment 1+2 (2091 +/- 1323 pmol/L vs. 804 +/- 398 pmol/L, P <0.001), plasmin/alpha2-antiplasmin complexes (410 +/- 220 microg/L vs. 214 +/- 92 microg/L, P <0.001), and thrombomodulin (37 +/- 24 ng/mL vs. 27 +/- 10 ng/mL, P <0.001). These levels did not differ between patients with or without thrombosis. CONCLUSIONS: Thrombophilic factors do not seem to explain most thromboses in Behçet's disease. There is increased thrombin generation, fibrinolysis, and thrombomodulin in Behçet's disease, but these abnormalities are not related to thrombosis.

Adolescent↗
PubMed2002

Viral etiopathogenesis of Sjögren's syndrome: role of the hepatitis C virus.

Patients with hepatitis C virus (HCV) chronic infection present some extrahepatic manifestations that may mimic the clinical, immunologic and histological manifestations of primary Sjögren's syndrome (SS). Thus, HCV patients with sicca symptomatology and positive autoantibodies could be misdiagnosed as a 'primary' SS. Nevertheless, there are several clinical and immunologic features that could help us differentiate both processes.

Animals↗
PubMed2002

Pregnancy outcome in systemic lupus erythematosus: good news for the new millennium.

Systemic lupus erythematosus (SLE) is the autoimmune disease that most commonly compromises pregnancy. Moreover, the relationship between SLE and pregnancy is in both directions. However, in the recent years there has been a great change in the perception of the effects of pregnancy on SLE flares and of SLE on pregnancy outcome (both fetal and maternal). The current experience indicates that pregnancy in patients with SLE should not be regarded as an unacceptable high risk condition for the mother or her baby provided that careful planning of conception and multidisciplinary monitoring and treatment are carried out.

Antiphospholipid Syndrome↗
PubMed2002

Anti-chromatin (anti-nucleosome) autoantibodies.

Anti-chromatin autoantibodies were one of the first autoantibodies ever detected since they make up the majority of antibodies causing LE Cell formation. Anti-chromatin autoantibodies have had many names over the last few decades: LE cell factor; anti-nucleosome; anti-deoxyribonucleoprotein (DNP); and anti-(H2A-H2B-DNA). These autoantibodies are found in approximately 75% of people with systemic lupus erythematosus and up to 100% of people with drug-induced lupus. They are also found in 20-50% of patients with autoimmune hepatitis type I (lupoid hepatitis). Anti-chromatin are not generally found in any other disease, thus showing very good sensitivity and specificity for patients with lupus, drug-induced lupus and lupoid hepatitis. A number of studies have shown that in patients with lupus, anti-chromatin often correlates better with kidney disease than anti-DNA. Recent genetic analyses of murine models of lupus have identified at least three loci that work together to cause anti-chromatin antibodies and glomerulonephritis in mice. It will be an important breakthrough when the functions of the genes at these loci are identified.

Animals↗
PubMed2002

True anti-anionic phospholipid immunoglobulin M antibodies can exert lupus anticoagulant activity.

True (cofactor-independent) anticardiolipin antibodies (aCL) are thought to lack lupus anticoagulant (LA) activity and pathogenic potential. A serum monoclonal immunoglobulin Mlambda (mIgMlambda) with aCL and LA activities found in a man with a splenicIgMlambda+ B-cell lymphoplasmacytic lymphoma (LPL) without thrombotic events has been characterized. LPL-derived hybridoma clones (designated HY-FRO) producing the serum mIgMlambda were obtained. mIgMlambda secreted by HY-FRO grown in protein-free culture medium, like that purified from serum, (i) showed binding, in a cofactor-free system, to solid-phase CL and phosphatidylserine (PS) and to the membrane of PS-expressing cells (apoptotic cells and activated platelets); (ii) failed to bind neutral phospholipids (PL), beta2Glycoprotein, histone, ssDNA, dsDNA, human IgG and umbilical vein endothelial cells. Absorption with apoptotic cells abolished its binding to anionic plate-bound CL and PS. IgMlambda-FRO used poorly mutated VH and Vlambda region genes, with a pattern that was inconsistent with an antigen-driven selection. Basic amino acids were present in the IgH complementarity determining region 3 (CDR3), which can be important for binding to anionic PL. These findings demonstrate unequivocally that true anti-anionic PL IgM antibodies can exert LA and indicate this anti-PL type does not involve thrombophilia.

Aged↗
PubMed2002

Th1/Th2 cytokine imbalance in patients with Sjögren syndrome secondary to hepatitis C virus infection.

OBJECTIVE: To investigate if the serum immunologic profile, as delineated by serum circulating levels of Th1/Th2 cytokines and autoantibodies, is different in patients with Sjögren syndrome (SS) with and without hepatitis C virus (HCV) infection. METHODS: This study included 20 patients with HCV-related SS and 47 consecutive patients with primary SS. All fulfilled 4 or more of the modified 1996 European criteria for SS. Serum levels of interleukin (IL)-2 (pg/mL), srIL-2 (pM), tumor necrosis factor (TNF)-alpha (pg/mL), IL-6 (pg/mL), and IL-10 (pg/mL) were determined using enzyme immunoassay. We also analyzed the following immunologic tests: anti-nuclear antibodies (ANA), anti-mitochondrial antibodies (AMA), anti-parietal cell antibodies (PCA), anti-smooth muscle antibodies (SMA), anti-liver-kidney microsome antibodies type-1 (LKM-1), anti-Ro/SS-A, anti-La/SS-B, rheumatoid factor (RF), complement factors (C3 and C4), and cryoglobulins. RESULTS: Of the 20 patients with HCV-related SS, 18 were women and 2 men (mean age, 66 years). Patients with HCV-related SS had a different cytokine profile compared with patients with primary SS, with higher circulating levels of IL-6 (73.6 v 33.0 pg/mL, P =.045), IL-10 (6.7 v 3.1 pg/mL, P =.01), srIL-2 (124.6 v 72.7 pM, P =.001), and TNF-alpha (59.8 v 31.7 pg/mL, P =.003). The main immunologic features were ANA, detected in 75% of patients, RF in 63%, cryoglobulinemia in 50%, hypocomplementemia in 40%, SMA in 30%, PCA in 25%, anti-Ro/SS-A in 25%, AMA in 20% and anti-La/SS-B in 16%. When compared with primary SS patients, those with HCV-related SS had a higher prevalence of AMA (20% v 2%, P =.025), hypocomplementemia (40% v 11%, P =.015), and cryoglobulinemia (50% v 12%, P =.003). CONCLUSION: Although chronic HCV infection may mimic the main clinical, histologic and immunologic features of primary SS, patients with HCV-related SS showed some differentiated characteristics, including a predominant Th2 pattern and a higher frequency of cryoglobulinemia and hypocomplementemia (features closely related to HCV). This suggests that the SS observed in some HCV patients should be interpreted as one of the extrahepatic manifestations of chronic HCV infection.

Autoantibodies↗
PubMed2002

Raynaud's phenomenon in primary Sjögren's syndrome. Prevalence and clinical characteristics in a series of 320 patients.

OBJECTIVE: To determine the prevalence of Raynaud's phenomenon (RP) in a large series of patients with primary Sjögren's syndrome (SS) and to identify the clinical and immunological features related to its presence. METHODS: In a cross sectional study, we investigated 320 consecutive patients with primary SS (294 women, 26 men; mean age at onset 60 yrs, range 16-87 yrs). All patients fulfilled 4 or more of the diagnostic criteria for SS proposed by the European Community Study Group in 1993. Diagnosis of RP in patients with SS was defined as intermittent attacks of digital pallor and/or cyanosis in the absence of any other associated disease or anatomical abnormalities. RESULTS: RP was present in 40 (13%) patients. All were women, with a mean age of 57 yrs (range 18-78). RP preceded onset of sicca symptomatology in 18 (45%) patients. The main triggering factor was exposure to cold, which induced RP in all patients, while emotional stress was a factor in 12 patients, as was job related predisposition in 2. Fifteen (38%) patients required pharmacological treatment with calcium channel blockers (12 patients) or angiotensin converting enzyme inhibitors (2 patients) during colder months, and one patient required treatment with intravenous prostacyclin for ischemic complications. Compared with SS patients without RP, those with RP showed a higher prevalence of articular involvement (50 vs 31%; p = 0.031), cutaneous vasculitis (30 vs 11%; p = 0.003), antinuclear antibodies (95 vs 65%; p < 0.001), anti-Ro/SSA (59 vs 31%; p < 0.001) and anti-La/SSB antibodies (44 vs 20%, p = 0.003). CONCLUSION: We found RP in 13% of patients with primary SS, in almost half of whom RP was the first autoimmune symptomatology. These patients constituted a subset of SS with a higher frequency of some extraglandular features and positive immunological markers. The clinical course of RP seems to be milder in patients with primary SS than in those with other systemic autoimmune diseases such as systemic sclerosis, with no vascular complications and pharmacological treatment needed in only 40% of patients.

Adolescent↗
PubMed2002

Lessons from the "Euro-Lupus Cohort".

The "Euro-Lupus Cohort" is composed by 1,000 patients with systemic lupus erythematosus (SLE) that have been followed prospectively since 1991. These patients have been gathered by a European consortium - the "Euro-Lupus Project Group". This consortium was originated as part of the network promoted by the "European Working Party on SLE", a working group created in 1990 in order to promote research in Europe on the different problems related to this disease. The "Euro-Lupus Cohort" provides an updated information on the SLE morbidity and mortality characteristics in the present decade as well as defines several clinical and immunological prognostic factors.

Adolescent↗
PubMed2002

Catastrophic antiphospholipid syndrome: proposed guidelines for diagnosis and treatment.

The term "catastrophic" antiphospholipid syndrome (APS) was introduced to define an accelerated form of APS resulting in multi-organ failure. Although patients with the catastrophic form represent less than 1% of all patients with APS, they are usually in a life-threatening medical situation that requires high clinical awareness. In this article, we propose guidelines for the diagnosis and treatment of patients with catastrophic APS, based on the cumulated published experience of 130 cases with this syndrome. We believe that it is essential that this syndrome should be diagnosed early and treated aggressively. The combination of high doses of heparin and corticosteroids plus intravenous gamma globulins or plasmapheresis is proposed as the treatment of choice in patients with this severe condition. In addition, preventive measures in patients with APS may be effective to avoid the development of catastrophic APS. We recommend that these proposed guidelines be tested in future prospective, collaborative studies to assess clearly the real prevalence and the best therapy for this life-threatening condition.

Journal Article↗
PubMedDate not supplied

Autoantibodies and prediction of reproductive failure.

PROBLEM: To determine which autoantibodies are associated with reproductive failure. METHOD OF STUDY: Sera from 269 patients with autoimmune disease and/or reproductive failure were analyzed for anti-phospholipid (aPL), anti-annexin-V, anti-lactoferrin, anti-thyroglobulin, anti-thyroid peroxidase, anti-prothrombin, anti-nuclear, and anti-saccharomycetes cerevisiae antibodies (ASCA), by enzyme-linked immunosorbent assay. Patients were classified as: recurrent pregnancy loss (RPL), infertility, and autoimmune diseases. The results were compared with those of 120 healthy volunteers. RESULTS: In autoimmune diseases, the prevalence of anti-prothrombin, anti-annexin, anti-phospholipid and anti-nuclear antibodies was significantly higher than in the control group, OR 11.0 [CI, 3.5-35.2], 33 [CI, 7.2-174.2], 13 [CI, 1.4-309.7], and 16.1 [CI 2.4-122], respectively. In infertility, the antibodies with significantly higher levels than controls were: aPL OR, 5.11 [CI 1.2-25.4], and anti-prothrombin antibodies, OR, 5.15 [CI, 2.1-12.7]. In RPL, ASCA, anti-prothrombin and aPL were more prevalent than in controls, OR 3.9 [CI, 1.5-10.6], 5.4 [CI, 2.4-12.5] and 4.8[CI, 1.2-22.2] for each antibody, respectively. Anti-prothrombin antibodies and aPL were more significantly associated with late pregnancy losses than early losses. CONCLUSION: ASCA antibodies have not previously been described in RPL. Nor are anti-prothrombin antibodies usually assessed in infertility or RPL. If these results are confirmed in further studies, these antibodies might be assessed routinely in reproductive failure.

Abortion, Spontaneous↗