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R Cervera

Publications and source records attributed to R Cervera.

212 records · Page 12Linked to original sources
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Circulating levels of Th1/Th2 cytokines in patients with primary Sjögren's syndrome: correlation with clinical and immunological features.

OBJECTIVE: To analyse the circulating levels of Th1 and Th2 cytokines in patients with primary Sjögren's syndrome (SS), as well as to investigate their association with clinical and immunological manifestations. METHODS: We included 62 consecutive patients (58 women and 4 men) seen in our Unit. All patients fulfilled 4 or more of the European diagnostic criteria for SS. Serum levels of IL-6 (pg/mL), IL-2 (pg/mL), srIL-2 (pM), TNFalpha (pg/mL) and IL-10 (pg/mL) were determined using a solid phase enzyme immunoassav performed on microtiter plate. RESULTS: When compared with the control group, high levels of Th1 (11-2, srIL-2) and Th2 (IL-6, IL-10) cytokines were detected in SS patients, although only IL-6 levels reached statistical significance. On the other hand, analysis of the mean serum concentrations of cytokines showed distinct patterns of elevated cytokines according to the organ involved, and elevated levels of IL-6 (126.5 v 20.6 pg/mL, p < 0.05) and IL-10 (10.6 v 2.2 pg/mL, p < 0.005) were observed in those patients with liver involvement. Analysis of the cytokine levels according to the presence of immunological features showed: higher levels of srIL-2 (95.6 v 54.0 pM, p < 0.05) in patients with anti-Ro/SS-A antibodies; increased levels of srIL-2 (111.4 v 59.4 pM, p < 0.05) in patients with antiLa/SS-B antibodies; higher levels of srIL-2 (90.4 vs 50.8 pM, p < 0.05) and TNFalpha (37.9 v 22.6 pg/mL, p = 0.001) in patients with RF and higher levels of IL-6 (88.0 v 23.1 pg/mL, p < 0.05) in patients with cryoglobulins and in those with hypocomplementemia (130.3 vs 21.0 pg/mL, p < 0.05). CONCLUSION: We found a significant elevation of several circulating cytokines in some clinical and immunological subsets of patients with primary SS. These cytokine patterns may be markers for specific extraglandular involvement in SS and could be of interest in assessing the response to treatment protocols or in monitoring the disease evolution.

Adult↗
PubMedDate not supplied

Relationship of oncogenes (sFas, Bcl-2) and cytokines (IL-10, alfa-TNF) with the activity of systemic lupus erythematosus.

BACKGROUND: Different oncogenes (Fas and bcl-2) and diverse cytokines (IL-10 and alfa-TNF) may have an effect on the regulation of apoptosis. The majority of studies to date have evaluated only one or two of these elements independently and it is difficult to obtain a global view of apoptosis disregulation in the pathogenesis of systemic lupus erythematosus (SLE) and their role in disease activity. The aim of this study was to evaluate serum levels of sFas, bcl-2, IL-10 and alfa-TNF in human SLE patients and to analyze their relationship with disease activity and with regulation of the apoptotic process. PATIENTS AND METHODS: Serum levels of sFas and cytokines IL-10 and alfa-TNF were studied by enzyme-linked immunoabsorbent assay. Bcl-2 antigen expression was analyzed in lysated lymphocytes from 51 SLE patients. The disease activity was analyzed according to the SLE disease activity index (SLEDAI). RESULTS: SLE patients had higher levels of sFas (p=0.0006) and alfa-TNF (p<0.0001) than the control group. No relationship was found between the levels of bcl-2 and IL-10 from SLE patients and the control group. However, there was a significant correlation between SLEDAI and bcl-2 (p<0.001) and IL-10 levels (p=0.004). In contrast, we found that sFas and alfa-TNF were not related with disease activity. A significant correlation of sFas with alfa-TNF serum levels (p=0.003, R= +0.41) and bcl-2 antigen expression (p=0.02, R=+0.32) was observed. CONCLUSION: sFas and alfa-TNF serum levels are increased in SLE patients. sFas levels seems to be secondary to alfa-TNF action, which is enhanced in inflammatory conditions such as SLE. Bcl-2 antigen expression and IL-10 serum levels are related to the maintenance of SLE activity. These alterations may interfere with the apoptotic process, promoting lymphocyte hyperactivity secondary to increased cytokine levels, and causing the characteristic features of SLE.

Adolescent↗
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Low values of creatine kinase in systemic lupus erythematosus. Clinical significance in 300 patients.

OBJECTIVE: To study creatine kinase (CK) activity in a large series of patients with systemic lupus erythematosus (SLE) and identify the clinical and immunological features related to reduced levels. METHODS: In a cross-sectional study, serum CK activity was measured in 300 consecutive patients with SLE (271 females and 29 males, with a mean age of 36 years). All patients fulfilled the 1982 revised criteria of the American College of Rheumatology. RESULTS: Low serum CK levels (< 33 IU/L) were detected in 118 (39%) of SLE patients. When compared to SLE patients with normal serum CK levels, those with SLE and low serum CK levels had a higher frequency of fever (53% vs. 34%, p = 0.017), renal involvement (43% vs. 27%, p = 0.004), and hemolytic anemia (13% vs. 6%, p = 0.037). In addition, SLE patients with low CK values also presented lower values of hemoglobin, total proteins, albumin, cholesterol and triglycerides, higher values of ESR and low C3 (44% vs. 27%, p = 0.004), C4 (57% vs. 37%, p = 0.001) and CH50 levels (60% vs. 41%, p = 0.02). We analysed in 69 patients the correlation between CK and 24-hour proteinuria values, and found that those with a 24-hour proteinuria > 1500 mg/day showed lower CK values than those with proteinuria < 1500 (31.95 vs 63.84 IU/L, p = 0.046). CONCLUSION: We observed that serum CK levels were reduced in 39% of SLE patients. Reduced serum CK activity was significantly related to some clinical (fever, nephropathy), hematological (high ESR, hemolytic anemia) and immunological (hypocomplementemia) features, which relate to disease activity. This suggest that reduced CK activity might be inversely correlated to inflammatory activity in SLE.

Adult↗
PubMedDate not supplied

Behçet's disease and hereditary periodic fever syndromes: casual association or causal relationship?

OBJECTIVE: Mutations in the MEFV and the type 1 TNF receptor (TNFRSF 1A) genes have recently been linked to familial Mediterranean fever (FMF) and TNF receptor-associated periodic syndrome (TRAPS), respectively. A higher prevalence of Behçet's disease (BD) among FMF patients has been described compared to the general population. The aim of this study was to evaluate whether FMF TRAPS and BD could be genetically related. METHODS: We screened a cohort of 50 BD patients and 100 healthy subjects for the common MEFV and TNFRSF 1A mutations. An initial screening of exons 10 and 2 of the MEFV gene and exon 4 of the TNFRSF 1A was performed in all chromosomes. RESULTS: The heterozygous MEFV mutation (K695R) was found in one (2%) BD patient. Analysis for FMF mutations in the control group revealed that 5 (5%) individuals bore MEFV gene mutations (3 were heterozygous for the E148Q and 2 were heterozygous for the A744S). At codon 202, there were no differences in allele frequencies between BD and control population: 73%R 27%Q in the BD patients vs 75%R 25%Q in controls. Concerning mutations in the TNFRSF 1A gene, the R92Q mutation was present in heterozygous state in one (2%) BD patient and in 4 (4%) controls without differences between allele frequencies: 99%R 1%Q in BD patients vs 98%R 2%Q in controls, respectively. There was no association between the clinical manifestations of BD patients and the presence of a particular polymorphism or a mutation. CONCLUSIONS: Neither FMF nor TRAPS are genetically associated with BD in our cohort of Spanish patients.

Behcet Syndrome↗
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Late thrombotic events in patients with temporal arteritis and anticardiolipin antibodies.

IgG and IgM isotypes of anticardiolipin (aCL) antibodies were measured in a group of 40 patients with biopsy-proven temporal arteritis (TA), 13 of them with ischemic complications related to the disease. High levels of aCL antibodies were found in only 3 (7.5%) patients. Two had high titres of both IgG and IgM isotypes and the third had high titres of the IgM isotype. No relationship between aCL antibody positivity and the development of any of the classical early occlusive complications of TA was found. However, 2 out of the 3 patients with positive aCL antibody titres later developed ischemic phenomena on conventional corticosteroid treatment. This finding suggests that aCL antibodies could perhaps have a role in the development of the late ischemic complications that occasionally occur in adequately treated TA patients.

Aged↗
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Isotype distribution and clinical significance of antibodies to cardiolipin, phosphatidic acid, phosphatidylinositol and phosphatidylserine in systemic lupus erythematosus: prospective analysis of a series of 92 patients.

OBJECTIVE: To determine the prevalence and correlation with clinical manifestations of the IgG and IgM isotypes of antibodies to cardiolipin (aCL), phosphatidic acid (aPA), phosphatidylinositol (aPI) and phosphatidylserine (aPS) in patients with systemic lupus erythematosus (SLE). METHODS: Clinical and laboratory features of 92 consecutive unselected patients with SLE were prospectively studied over two years. aCL, aPA, aPI and aPS were determined by ELISA. RESULTS: aCL were detected in 34 (37%) patients, aPA in 26 (28%), aPI in 22 (24%), and aPS in 29 (32%). A significant association was found between the appearance of thrombosis and the presence of IgG aCL (p < 0.001) and IgG aPS (p < 0.05). A significant association was also found between thrombocytopenia and the presence of IgG aCL (p < 0.001), IgG aPA (p < 0.01), IgG aPI (p < 0.05), and IgG aPS (p < 0.001). The development of hemolytic anemia was associated with the detection of IgM aCL (p < 0.001), IgM aPA (p < 0.05), IgM aPI (p < 0.001), and IgM aPS (p < 0.01). CONCLUSION: We found a relatively high prevalence of aCL, aPA, aPI and aPS in our SLE population and confirmed the presence of a correlation between the IgG isotype of these antibodies and thrombosis and thrombocytopenia, and also between the IgM isotype and hemolytic anemia. These results demonstrate the variety of antiphospholipid antibodies that can be detected in SLE patients, as well as their association with the clinical manifestations of the antiphospholipid syndrome.

Adolescent↗
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Antiphospholipid antibodies in primary Sjögren's syndrome: prevalence and clinical significance in a series of 80 patients.

OBJECTIVE: To determine the prevalence and clinical significance of antiphospholipid antibodies (aPL) in a cohort of patients with primary Sjögren's syndrome (SS). METHODS: Eighty patients with primary SS were studied prospectively. The prevalence of aPL and characteristics of the clinical and laboratory features of these patients were compared with those of the following groups of patients: (i) 50 patients with SS associated with systemic lupus erythematosus (SLE); (ii) 100 patients with SLE without SS; and (iii) 100 healthy blood donors from the blood bank of our hospital. RESULTS: Only 11 (14%) patients with primary SS were found to have aPL (anticardiolipin antibodies or lupus anticoagulant, or both) in their sera, but anti beta 2-glycoprotein I antibodies were not detected in any patient. In contrast, aPL were detected in 12 (24%) patients with SS secondary to SLE and in 21 (21%) patients with SLE without SS. None of the healthy controls presented aPL in their sera. Patients with primary SS presented a lower prevalence of thrombocytopenia (p < 0.05) and livedo reticularis (p < 0.01) compared with the other two groups of patients. No patient with primary SS was diagnosed as having an antiphospholipid syndrome (APS), while 4 (8%) patients with secondary SS and 9 (9%) with SLE without SS were found to have APS (p < 0.05). CONCLUSION: In patients with primary SS, aPL are present in a lower percentage than in patients with SS secondary to SLE or in patients with SLE without SS. The presence of aPL in these primary SS patients is not associated with the clinical events of APS.

Adult↗
PubMedDate not supplied

Antiphospholipid syndrome without antiphospholipid antibodies at the time of the thrombotic event: transient 'seronegative' antiphospholipid syndrome?

The antiphospholipid syndrome (APS) is characterized by the presence of venous and arterial thrombosis, recurrent fetal losses and thrombocytopenia, associated with the presence of antiphospholipid antibodies (aPL). This syndrome may be "primary" or may be associated with other diseases, mainly systemic lupus erythematosus (SLE). However, some patients present the clinical picture of this syndrome but without evidence of aPL in their serum. The term "seronegative" APS has been proposed to categorize these patients. Here with we present two patients with seronegativity for aPL at the time of a thrombotic event, but in whom these antibodies were detected 2 and 7 months later.

Adult↗
PubMedDate not supplied

Lack of correlation between tumor markers (CA 125 and SCC) and systemic lupus erythematosus activity.

BACKGROUND: Recently, tumor markers (CA 125 and SCC) have been suggested as possible activity markers of systemic lupus erythematosus (SLE), but study results have been contradictory. OBJECTIVE: The aim of this study was to evaluate the possible relationship between CA 125 and SCC serum levels and SLE activity. PATIENTS AND METHODS: Serum levels of CA 125 from 59 patients and levels of SCC from 53 patients with SLE were analyzed. Both tumor markers were determined by ELISA, considering 35 U/ml (CA 125) and 2.5 ng/ml (SCC) respectively as the upper limit of normality. The serum levels of these tumor markers were correlated with the SLE disease activity index (SLEDAI). RESULTS: The CA 125 concentrations in active SLE (mean 13.8 + 15.3) were similar to those in inactive patients (mean 13.1 + 11.7 U/ml). Significantly high CA 125 serum levels were found only in SLE patients with nephrotic syndrome (p = 0.001). No significant differences were found in SCC serum levels in SLE patients with (mean 0.9 +/- 0.8 ng/ml) or without activity (mean 1.1 +/- 1.3 ng/ml). Likewise, no relationship between SCC serum levels and parameters related to SLE activity were found, excluding slight increases associated with renal failure. CONCLUSIONS: The correlation that some authors have found between elevated serum levels of CA 125 and SLE activity is only associated with the presence of nephrotic syndrome. Likewise, SCC is not related with SLE activity and the increases found may be due to renal failure.

Antigens, Neoplasm↗
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Anti-neutrophil cytoplasmic antibodies in 566 European patients with systemic lupus erythematosus: prevalence, clinical associations and correlation with other autoantibodies. European Concerted Action on the Immunogenetics of SLE.

OBJECTIVES: To evaluate, in a cohort of 566 patients with systemic lupus erythematosus (SLE) drawn from 11 European centres: (i) the prevalence of ANCAs and their subspecificities in a large series of European SLE patients; (ii) the possible associations of ANCA with the most common clinical manifestations of the disease; and (iii) whether ANCAs correlate with some of the autoantibodies commonly found in SLE. METHODS: ANCA detection was performed by indirect immunofluorescence (IIF), and by ELISA for lactoferrin (LF), myeloperoxydase (MPO), proteinase3 (PR3) and lysozyme (LZ) subspecificities. RESULTS: The prevalence of ANCA was 16.4% (IIF). The prevalence of LF was 14.3%, LZ 4.6%, MPO 9.3%, and PR3 1.7%. Our results show that ANCA is associated with certain clinical manifestations of SLE. In particular, positive correlations were found between IIF ANCA and serositis (p = 0.026), livedo reticularis (p = 0.01), venous thrombosis (p = 0.03) and arthritis (p = 0.04), while anti-LF antibodies were associated with serositis (p = 0.05) and livedo reticularis (p < 10(-3). Nevertheless, multivariate analysis demonstrated that other autoantibodies, such as aCL and SSA/Ro, are more closely correlated than ANCA with some of the aforementioned clinical features. CONCLUSION: Our results demonstrate that ANCA are detectable in SLE sera and that some of them are associated with particular clinical manifestations. Whether ANCA plays a direct pathogenetic role in the vascular damage of SLE or only represents an epiphenomenon or a marker of disease activity remains to be elucidated.

Adolescent↗
PubMedDate not supplied

Association of 16/6 and SA1 anti-DNA idiotypes with anticardiolipin antibodies and clinical manifestations in a large cohort of SLE patients. European Concerted Action on the Immunogenetics of SLE.

OBJECTIVE: The SA1 and 16/6 idiotypes can be found in some patients with systemic lupus erythematosus (SLE) or anti-phospholipid syndrome (APS). The aim of this study was to ascertain the prevalence of these idiotypes in a large cohort of SLE patients, and to determine whether their presence is correlated with the anticardiolipin (aCL) and anti-dsDNA antibodies or with the clinical manifestations of SLE. METHODS: 492 SLE patients were evaluated for clinical manifestations of SLE and were assigned a disease severity score. ds-DNA autoantibodies, aCL autoantibodies of the IgM, IgG and IgA isotypes, and SA1 and 16/6 idiotypes were also determined in these patients. RESULTS: The prevalence of the SA1 and 16/6 idiotypes in the 492 SLE patients was found to be 11% and 5.1%, respectively, and these idiotypes were significantly more prevalent in the patients who had aCL antibodies of either the IgG, IgM or IgA isotypes. Moreover, while the 16/6 idiotype was not associated with the clinical manifestation of either SLE or APS, the SA1 idiotype was found significantly more frequently in patients who had vascular events Raynaud's phenomenon or hemolytic anemia (p = 0.016, 0.01, 0.01, respectively). CONCLUSION: SLE patients with the SA1 idiotype may run a higher risk of developing vascular events, Raynaud's phenomenon or hemolytic anemia. These clinical manifestations can be attributed to both SLE and secondary APS when aCL autoantibodies are also found. These results indicate that the possible pathogenicity of certain idiotypes in SLE cannot be excluded.

Adolescent↗