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Renato Alberto Sinico

Publications and source records attributed to Renato Alberto Sinico.

10 recordsLinked to original sources
PubMed2006

Renal involvement in Churg-Strauss syndrome.

BACKGROUND: Churg-Strauss syndrome (CSS) is a rare disorder characterized by asthma, eosinophilia, and systemic vasculitis. Renal involvement is not regarded as a prominent feature, and its prevalence and severity vary widely in published reports that usually refer to small series of selected patients. METHODS: We examined the prevalence, clinicopathologic features, and prognosis of renal disease in 116 patients with CSS. RESULTS: There were 48 men and 68 women with a mean age of 51.9 years (range, 18 to 86 years). Signs of renal abnormalities were present in 31 patients (26.7%). Rapidly progressive renal insufficiency was documented in 16 patients (13.8%); urinary abnormalities, 14 patients (12.1%); and chronic renal impairment, 1 patient. There were 3 additional cases of obstructive uropathy. Sixteen patients underwent renal biopsy, which showed necrotizing crescentic glomerulonephritis in 11 patients. Other diagnoses were eosinophilic interstitial nephritis, mesangial glomerulonephritis, and focal sclerosis. Antineutrophil cytoplasmic antibody (ANCA) was positive in 21 of 28 patients (75.0%) with nephropathy versus 19 of 74 patients without (25.7%; P < 0.001). In particular, all patients with necrotizing crescentic glomerulonephritis were ANCA positive. After a median follow-up of 4.5 years, 10 patients died (5 patients with nephropathy) and 7 patients developed mild chronic renal insufficiency. Five-year mortality rates were 11.7% (95% confidence interval, 3.9 to 33.3) in patients with nephropathy and 2.7% (95% confidence interval, 0.7 to 10.7) in those without (P = 0.10). CONCLUSION: Renal abnormalities are present in about one quarter of patients with CSS. The prevailing picture is ANCA-associated necrotizing crescentic glomerulonephritis; however, other forms of nephropathy also may occur. Outcome and long-term follow-up usually are good.

Adolescent↗
PubMed2006

A new oligonucleotide-based ELISA for the detection of anti-double-stranded DNA antibodies.

The detection and measurement of antibodies to double-stranded (ds) DNA is important in the diagnosis and monitoring of patients with systemic lupus erythematosus (SLE). Several methods are available for their determination but none of them is completely satisfactory. Usually, purified dsDNA from different sources is used as antigen in the solid (enzyme-linked immunosorbent assay, ELISA) or liquid phase (Farr assay). Alternatively, anti-dsDNA antibodies can be demonstrated by immunofluorescence, using the haemoflagellate Crithidia luciliae (CLIFT). We have developed a new oligonucleotide-based anti-dsDNA ELISA in which dsDNA, constituted of a 5'photobiotinylated nucleic acid probe and its highly specific complementary oligonucleotide, is formed onto the solid-phase. To do that, a 40 bp probe is coated on the microplate wells via streptavidin-biotin bond and the in vitro (in solid-phase) developed hybrid between probe and its complementary helix used as capturing antigen. The assay has proved to be specific and the several experiments performed to ascertain the absence of single-stranded DNA (ssDNA) contamination and/or non specific binding to plastic, streptavidin, probe (without complementary chain) have all excluded any significant interference. To evaluate the clinical performance of this new assay, 114 serum samples from 68 SLE patients and 85 samples from 85 disease controls, in addition to 30 blood donors, were studied. The results were compared with commercial ELISAs, Farr assay and indirect immunofluorescence. The sensitivity and specificity were 66.2 and 96.4%, respectively, comparable and even better than those of the commercially available anti-dsDNA kits. Anti-dsDNA antibody levels, measured with the oligonucleotide-ELISA, correlated with SLE clinical activity determined using the European Consensus Lupus Activity Measurement (ECLAM) (r = 0.59, p < 0.0001). In conclusion, this assay has proved to be reproducible, and the results correlate well with other standard anti-dsDNA assays. The features of this new assay make it promising for clinical use.

Antibodies, Antinuclear↗
PubMed2005

Anti-glomerular basement membrane antibodies in the diagnosis of Goodpasture syndrome: a comparison of different assays.

BACKGROUND: The role of anti-glomerular basement membrane (GBM) antibodies in the pathogenesis of Goodpasture syndrome (GPS) is firmly established. Untreated, the disease may follow a fulminating course. Early identification of patients has important implications in terms of management and prognosis. Therefore, a diagnostic test for the determination of circulating anti-GBM antibodies, of very high sensitivity and specificity, is necessary. A number of assays, using different antigenic substrates, are available, but studies comparing the 'performances' of the different tests are scarce. METHODS: The aim of our work was to evaluate the sensitivity and specificity of four immunoassay-based anti-GBM antibodies kits. Thirty-four serum samples from 19 GPS patients, 41 pathological and 28 normal controls were studied retrospectively (the follow-up samples were not included in the analysis of performance data). Cut-off limits were derived from receiver operating characteristics curve analysis. RESULTS: All the assays showed a comparable good sensitivity (between 94.7 and 100.0%), whereas specificity varied considerably (from 90.9 to 100.0%). The better performance in terms of sensitivity/specificity was achieved by a fluorescence immunoassay which utilizes a recombinant antigen. CONCLUSION: All the assays have a good performance, with high sensitivity; however, the specificity may vary considerably.

Anti-Glomerular Basement Membrane Disease↗
PubMed2005

Value of a new automated fluorescence immunoassay (EliA) for PR3 and MPO-ANCA in monitoring disease activity in ANCA-associated systemic vasculitis.

The value of anti-neutrophil cytoplasmic antibody (ANCA) detection for monitoring disease activity in ANCA-associated systemic vasculitis (AASV) remains controversial. The aim of our work was to rate the performance of a new automated fluorescence PR3 and MPO-ANCA immunoassay (EliA) for monitoring disease activity in AASV. We evaluated 100 serum samples from 71 AASV patients (with Wegener's granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome) as well as sera from 58 pathological and 35 normal controls. In addition to PR3 and MPO-ANCA EliA, we performed indirect immunofluorescence and "homemade" PR3 and MPO-ANCA ELISA tests. In AASV patients, ANCA levels were correlated with disease activity, according to the Birmingham Vasculitis Activity Score (BVAS). We derived cutoff limits from receiver operating characteristic (ROC) curve analysis comparing AASV with pathological controls. Our results showed that EliA and ELISA had comparable sensitivity (76%) and specificity (95%). The analysis of active versus inactive status and correlation with ANCA levels showed a clear difference between BVAS Group I (score < or = 4) and BVAS Group II (scores > 4) (AUC = 0.86 vs. 0.72; relative risk [RR] = 2.4; P < 0.0001) for PR3-ANCA, but not for MPO-ANCA (AUC = 0.94 vs. 0.87; RR = 1.48; P = 0.46). Serial serum samples from 16 patients were examined in detail. For the majority of patients, for both PR3 and MPO-ANCA, change in titer was strongly associated with change in BVAS score. Our data showed a good correlation between ANCA titer (especially for PR3) and AASV disease activity. We recommend that ANCA titer be used to monitor AASV disease activity with the caveat that a few exceptions, in particular with MPO-ANCA, are possible.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed2005

Anti-C1q autoantibodies in lupus nephritis: prevalence and clinical significance.

Recently, anti-C1q autoantibodies have been proposed as a useful marker in systemic lupus erythematosus (SLE) since their occurrence correlates with renal involvement and, possibly, with nephritic activity. We aimed to evaluate the prevalence of anti-C1q antibodies in patients with SLE, with and without renal involvement, and to correlate these markers' presence and levels with the activity of the disease and nephropathy. We studied 61 patients with SLE, 40 of whom had biopsy-proven lupus nephritis; 35 patients with other connective tissue diseases; and 54 healthy controls. In addition, 18 lupus nephritis patients were followed up during the disease time course. Anti-C1q antibodies were measured using "homemade" ELISA with high salt concentration (1 M sodium chloride). High anti-C1q antibody titers (> 55 AU) were present in 27 of 61 (44%) SLE patients and in 4% and 0% of normal blood donors and pathologic controls, respectively. Anti-C1q antibodies were found in 60% of patients with lupus nephritis compared with only 14% of SLE patients without nephropathy (P < 0.05). Moreover, patients who were positive for anti-C1q antibodies had a higher European Consensus Lupus Activity Measurement (ECLAM) score (4.35 vs. 2.2); 89% of patients with active lupus nephritis showed high titers of anti-C1q antibodies compared with 0% of patients with inactive nephritis. Anti-C1q and anti-dsDNA antibodies agreed in 79% of cases. Our results confirm that anti-C1q antibodies are present in a significant percentage of SLE patients, and that their presence and levels correlate with disease activity-in particular, during renal flare-ups.

Antibodies, Anti-Idiotypic↗
PubMed2004

Early response to immunosuppressive therapy predicts good renal outcome in lupus nephritis: lessons from long-term followup of patients in the Euro-Lupus Nephritis Trial.

OBJECTIVE: In the Euro-Lupus Nephritis Trial (ELNT), 90 patients with lupus nephritis were randomly assigned to a high-dose intravenous cyclophosphamide (IV CYC) regimen (6 monthly pulses and 2 quarterly pulses with escalating doses) or a low-dose IV CYC regimen (6 pulses of 500 mg given at intervals of 2 weeks), each of which was followed by azathioprine (AZA). After a median followup of 41 months, a difference in efficacy between the 2 regimens was not observed. The present analysis was undertaken to extend the followup and to identify prognostic factors. METHODS: Renal function was prospectively assessed quarterly in all 90 patients except 5 who were lost to followup. Survival curves were derived using the Kaplan-Meier method. RESULTS: After a median followup of 73 months, there was no significant difference in the cumulative probability of end-stage renal disease or doubling of the serum creatinine level in patients who received the low-dose IV CYC regimen versus those who received the high-dose regimen. At long-term followup, 18 patients (8 receiving low-dose and 10 receiving high-dose treatment) had developed permanent renal impairment and were classified as having poor long-term renal outcome. We demonstrated by multivariate analysis that early response to therapy at 6 months (defined as a decrease in serum creatinine level and proteinuria <1 g/24 hours) was the best predictor of good long-term renal outcome. CONCLUSION: Long-term followup of patients from the ELNT confirms that, in lupus nephritis, a remission-inducing regimen of low-dose IV CYC followed by AZA achieves clinical results comparable with those obtained with a high-dose regimen. Early response to therapy is predictive of good long-term renal outcome.

Adolescent↗
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

Autoantibodies to proteinase 3 and myeloperoxidase in systemic sclerosis.

OBJECTIVE: We evaluated the prevalence and clinical significance of proteinase 3 (PR3-) and myeloperoxidase (MPO-) antineutrophil cytoplasmic antibodies (ANCA) in 115 patients with systemic sclerosis (SSc, scleroderma). METHODS: Sera were assayed by 2 independent centers, which used indirect immunofluorescence (IIF) and direct ELISA as screening tests. Inhibition-ELISA for PR3- and MPO-ANCA and PR3 capture-ELISA experiments were also performed. The clinical features of the ANCA positive were compared with those of the ANCA negative scleroderma patients. RESULTS: The IIF test revealed 5 P-ANCA positive sera (4.34%). Surprisingly, by ELISA 2 of these were PR3-ANCA positive, one was MPO-ANCA positive, and 2 were both PR3- and MPO-ANCA positive. In addition, 3 IIF negative sera were ELISA positive, 2 for PR3- and one for MPO-ANCA. ELISA results were confirmed by fluid phase inhibition experiments. Only 2 out of the 6 PR3-direct ELISA positive sera were positive by PR3-capture ELISA at low titers. Neither PR3- nor MPO-ANCA were significantly associated to any clinical feature of patients with SSc. CONCLUSION: As well as the previously described MPO-ANCA, even PR3-ANCA may be detected in some sera from patients with SSc. The IIF pattern and the negative results obtained with PR3-capture ELISA suggest that different epitopes from those recognized by vasculitis sera might be involved with PR3-ANCA in SSc, and show the importance of combining IIF and ELISA tests for ANCA detection.

Adult↗
PubMedDate not supplied

The use of laboratory tests in diagnosis and monitoring of systemic lupus erythematosus.

Clinical immunology laboratories play an essential role in diagnosis and monitoring of systemic lupus erythematosus (SLE). To obtain the best results in terms of diagnostic performance and clinical usefulness, the following recommendations should be fulfilled: Indirect immunofluorescence on Hep-2 cells remains the method of choice for the detection of anti-nuclear antibodies (ANA). The sensitivity of ANA test for SLE is very high (almost 100%) but its specificity low since ANA can be present in a number of different clinical conditions and even in normal controls. Anti-dsDNA antibodies are highly specific for SLE and present in a high proportion of SLE patients (40-80%). The method of choice for anti-ds DNA is the Farr assay; however, the necessity of using radioactive material decreases its applicability. As an alternative, immunofluorescence on Crithidia Luciliae can be used in the diagnostic phase for its high specificity. It is not advisable to use ELISA, in the diagnostic phase, due to its low specificity. The quantitative determination of anti-dsDNA is useful for monitoring patients, in particular in the presence of nephritis. For monitoring, a quantitative method should be used (Farr assay or ELISA). The detection of antibodies to extractable nuclear antigens (ENA) and to phospholipids (Lupus anticoagulant and anti-cardiolipin antibodies with a beta2 glycoprotein I-dependent method) are useful to identify subgroups of patients at risk for some clinical manifestations (i.e. anti-phospholipid syndrome). New assays (anti-C1q and anti-nucleosome antibodies) have been recently proposed for diagnosis (anti-nucleosome) and monitoring SLE patients (anti-C1q and anti-nucleosome antibodies), with promising results. Among biological parameters, urinary levels of monocyte chemoattranct protein 1 (MCP1) seem to be the most useful to monitor nephritis activity in lupus patients.

Clinical Laboratory Techniques↗