Predictive value of complement profiles and anti-dsDNA in systemic lupus erythematosus.

In a prospective study of 143 patients with systemic lupus erythematosus (SLE) the relation between clinical exacerbations, anti-dsDNA levels, and serum levels of complement components, C1q, C4, C3, C5, and C9 was investigated. In 33 out of these 143 patients a major clinical exacerbation of the disease developed. Evaluation of anti-dsDNA levels in relation to disease activity confirmed our earlier finding that anti-dsDNA levels rose before a major exacerbation and decreased after it. In the remaining 110 SLE patients a nearly constant anti-dsDNA level was seen, but none of these patients experienced a major exacerbation. In the 21 SLE patients who developed deterioration in renal function a decrease of C4 followed by decreases of C1q and C3 levels was seen first, starting about 25 to 20 weeks before the first signs of renal involvement. In the 12 SLE patients who developed an exacerbation without renal involvement an inconsistent profile of the complement components C4, C1q, and C3 was observed. C5 levels were hardly affected at all, while C9 levels were in general higher than normal during the exacerbation, irrespective of the type of exacerbation. These results show that, by following the complement and anti-dsDNA profiles, not only can exacerbations be predicted but also a pointer can be obtained about the pattern of disease well before the first clinical signs of an exacerbation appear.

Correlation of disease activity with circulating immune complexes (C1qbA) and complement breakdown products (C3D) in patients with systemic lupus erythematosus. A prospective study.

Most biologic effects of immune complexes are mediated through the activation of the complement system. The relationship between lupus disease activity and the presence of C3 breakdown products (C3d) and circulating immune complexes (CIC) as demonstrated with the C1q binding assay (C1qbA), was evaluated. Nearly all 13 systemic lupus erythematosus (SLE) patients had a stable disease course in this prospective study, nevertheless, in each patient the profiles of the serologic parameters were quite different. Despite the small number of investigated patients (13), it is concluded that irrespective of the disease activity, the serologic parameters could be either positive or negative. No relationship could be obtained between disease activity and the presence of C3d and/or CIC. Nor was there any evidence that the presence of CIC would indicate increased levels of C3 breakdown products (C3d). This observation argues against a pathogenetic significance of CIC detected by the C1qbA in SLE. In conclusion, the supposed link between the presence of CIC, consumption and activation of the complement system, and the activity of SLE needs further study.

Prognostic value of anti-dsDNA in SLE.

In a prospective longitudinal study 130 patients with systemic lupus erythematosus (SLE) were studied at least monthly for a relationship between the anti-dsDNA levels and disease activity. We observed 13 patients who developed 15 periods of exacerbations of their disease. All 15 exacerbations were preceded by a continuous increase of the anti-dsDNA levels. In 13 of the 15 exacerbations studied the exacerbation was preceded by an increase of anti-dsDNA with a doubling time (T2) of less than 6 weeks; in 4 of the 5 other exacerbations the T2 was less than 10 weeks. Four other patients with an increase of the anti-dsDNA levels showed no exacerbation. In these 4 patients the T2 was larger than 10 weeks. The other 113 patients did not show an increase of anti-dsDNA over the 2 years of monitoring and showed no signs of serious disease activity (no major symptoms). These observations suggest that an SLE patient who is followed up frequently and who shows a continuous increase of anti-dsDNA witha T2 shorter than 10 weeks is bound to develop an exacerbation.

Specificity in systemic lupus erythematosus of antibodies to double-stranded DNA measured with the polyethylene glycol precipitation assay.

Recently, a new radioimmunoassay--the polyethylene glycol (PEG) assay--was introduced to measure antibodies to double-stranded (ds) DNA. In this method, polyethylene glycol precipitation of formed 3H-DNA/antiDNA complexes is used instead of the ammonium sulfate precipitation used in the Farr assay. In contrast to the Farr assay, with which only high-avidity antibodies to dsDNA are detected, the PEG assay also reportedly measures anti-dsDNA of relatively low avidity. We studied whether this gain in antibody measurement results in loss of specificity for systemic lupus erythematosus. When the PEG assay was applied to a selected panel of 440 sera from patients with various well-defined autoimmune diseases and to a group of 197 normal human control sera, matched sex and age to the patients, the method was found to be fairly specific for systemic lupus erythematosus, although the sera from some patients with myasthenia gravis and some with autoimmune liver disease were also found positive. Screening of 352 additional serum specimens, sent to our laboratory for diagnostic reasons, revealed that, with the PEG assay, an extra population of relatively low-avidity antibodies to dsDNA--missed by the Farr assay--was detected. Upon clinical evaluation, we found that the patients in whom such antibodies were detected generally fulfilled a number of the preliminary criteria of the American Rheumatism Association for systemic lupus erythematosus, but that this diagnosis often was not made. We claim that the presence of low-avidity antiDNA characterizes a milder form of the disease in which patients often show only a single clinical feature of the disease. We conclude that results of the PEG assay add valuable diagnostic and clinical information to results obtained by the Farr assay.

Detection of anti-dsDNA as diagnostic tool.

The diagnostic significance of anti-dsDNA determinations was evaluated in 2 different groups of patients. When the immunofluorescence technique (IFT) with Crithidia luciliae and the Farr assay with 3H-labelled-PM2 DNA were applied to a selected panel of 536 sera from patients with various well-defined autoimmune diseases, positive results were obtained only with serum samples from patients with systemic lupus erythematosus (SLE). On the other hand when we screened 4431 sera sent to our laboratory for diagnostic reasons, we observed a high incidence of antibodies to dsDNA in patients who did not fulfil the preliminary American Rheumatism Association's criteria for SLE and did not have the diagnosis SLE. Furthermore, a significant number of the positive sera showed peculiar behaviour in that they were positive only in the IFT on Crithidia luciliae and not in the Farr assay.