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-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.

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.