Anti-ds-DNA antibodies - SLE Onset

2/05/03

Question: Does presence of anti double-stranded DNA (anti-ds-DNA) antibodies have predictive value for later onset of systemic lupus erythematosus (SLE)?

 Fulltext Available in EBSCO using ACADEMIC SEARCH PREMIER and the search term: (AN 4755907)

<1>

Unique Identifier:11439169

Authors: Arbuckle MR. James JA. Kohlhase KF. Rubertone MV. Dennis GJ. Harley JB.

Institution: Arthritis and Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.

Title: Development of anti-dsDNA autoantibodies prior to clinical diagnosis of systemic lupus erythematosus.

Source: Scandinavian Journal of Immunology. 54(1-2):211-9, 2001 Jul-Aug.

Abstract: Anti-double stranded (dsDNA) antibodies are of considerable diagnostic value and are thought to be involved in the pathogenesis of systemic lupus erythematosus (SLE). Fluctuations in anti-dsDNA antibody levels are also used as markers for disease activity and exacerbations. In this study we sought to evaluate the anti-dsDNA antibody level in serum samples collected before the onset of SLE diagnosis. A total of 130 SLE patients were identified with stored serum samples available prior to diagnosis within the US Department of Defense serum repository. All 633 sera available from these patients were screened for anti-dsDNA antibodies using an enzyme linked immunosorbant assay (ELISA). Within this cohort 55% of cases had detectable anti-dsDNA antibodies prior to SLE diagnosis. The onset of anti-dsDNA antibodies ranged from 9.3 years before to within the same month as diagnosis (with a mean onset 2.7 years before diagnosis). In order to assess for fluctuations in anti-dsDNA levels relative to diagnosis, cases were selected with at least two positive samples, one within 6 months and a second greater than 6 months prior to diagnosis (n = 26). Seven of these cases also had samples available shortly after diagnosis (< or = 6 months) for comparison. Fifty-eight percent of the 26 cases developed a significant rise in anti-dsDNA antibody levels within 6 months of diagnosis. A significant decline in anti-dsDNA levels ensued after diagnosis (and following treatment with corticosteroids) in all seven cases with samples available. Patients with a significant rise in anti-dsDNA antibodies at diagnosis were more likely to have renal disease than those who did not (66.7% compared to 27.3%, chi2 =3.94, P<0.05). These data suggest that anti-dsDNA antibodies are present in SLE patient sera much earlier than previously suspected. In addition, the data are consistent with increases in anti-dsDNA levels contributing to the onset of clinical illness in some patients with SLE. CAS Registry/EC Number 0 (Antibodies, Antinuclear). 9007-49-2 (DNA).

<15>

Unique Identifier:3872637

Authors: Swaak T. Smeenk R.

Title: Detection of anti-dsDNA as a diagnostic tool: a prospective study in 441 non-systemic lupus erythematosus patients with anti-dsDNA antibody (anti-dsDNA).

Source: Annals of the Rheumatic Diseases. 44(4):245-51, 1985 Apr.

Abstract: The diagnostic significance of anti-double-stranded deoxyribonucleic acid (anti-dsDNA) determination was evaluated in a prospective manner from 1974 to 1982 in a group of 441 patients without systemic lupus erythematosus whose sera were found to contain antibodies to dsDNA on routine screening (Farr assay). Within one year 69% (304) of these patients fulfilled the preliminary American Rheumatism Association (ARA) criteria for systemic lupus erythematosus (SLE). Eighty-two of the remaining 137 patients were followed up for several years. At the end of the study 52% of these patients had also developed systemic lupus erythematosus. Patients who developed systemic lupus erythematosus were characterised by the occurrence of relatively high avidity anti-dsDNA in the circulation compared with patients who did not develop systemic lupus erythematosus. It can be concluded that about 85% of patients without systemic lupus erythematosus with anti-dsDNA in the circulation will develop SLE within a few years. Taking into account the relative avidity of anti-dsDNA, as determined by calculation of Farr/polyethylene glycol (PEG) ratios, we conclude that patients with relatively high avidity anti-dsDNA are more prone to develop systemic lupus erythematosus than patients with relatively low avidity anti-dsDNA. CAS Registry/EC Number 0 (Antibodies, Antinuclear). 9007-49-2 (DNA).

<13>

Unique Identifier:2784621

Authors: Martini A. Lorini R. Zanaboni D. Ravelli A. Burgio RG.

Institution: Department of Pediatrics, University of Pavia, Italy.

Title: Frequency of autoantibodies in normal children.

Source: American Journal of Diseases of Children. 143(4):493-6, 1989 Apr.

Abstract: Very few data have been reported on the frequency of autoantibodies (AAs) in normal children. In the present study we investigated the frequency of 14 AAs in a total of 268 apparently normal children (151 boys and 117 girls; age range, 1 month to 14 years). Forty-one children (22 boys and 19 girls) were positive for at least one AA, usually in a low titer; two children were positive for two AAs. None of these children had a personal or family history of autoimmune diseases. The percentage of children positive for each AA was as follows: antinuclear, 3%; anti-smooth muscle, 2.6%; antireticulin, 2.6%; antimitochondrial, 1.1%; rheumatoid factor, 0.6%; antiribosomal, 0.4%; anti-gastric parietal cells, 5.2%; and anti-thyroid microsomal, 1.3%. Anti-double-stranded DNA, anti-intestinal epithelial cells, antiliver and antikidney microsomal, antithyroglobulin, anti-islet cells, and complement-fixing anti-islet cell antibodies were not detected in any serum. Fifteen of the 41 positive children were checked for the presence of AAs two years later; six (40%) were still positive, always for the same AA, without major differences in titer. Our results suggest that the overall frequency of AAs in apparently healthy children is quite similar to that reported in young adults; this AA positivity seems most often to represent a transient phenomenon. CAS Registry/EC Number 0 (Antibodies, Antinuclear). 0 (Autoantibodies). 0 (Reticulin). 9009-79-4 (Rheumatoid Factor).

<3>

Unique Identifier:10805357

Authors: Weinberg I. Vasiliev L. Gotsman I.

Institution: Division of Medicine, Hadassah University Hospital, and Hadassah Medical School, Hebrew University, Jerusalem, Israel.

Title: Anti-dsDNA antibodies in sarcoidosis.

Source: Seminars in Arthritis & Rheumatism. 29(5):328-31, 2000 Apr.

Abstract: BACKGROUND: Sarcoidosis is a chronic multisystem disorder characterized by an exaggerated cellular immune response to antigens with the production of various antibodies including rheumatoid factor and antinuclear antibodies (ANA). The prevalence and significance of antibodies to double-stranded DNA (anti-dsDNA) in sarcoid patients is unknown. The occurrence of anti-dsDNA antibodies is known to be a specific marker of systemic lupus erythematosus (SLE). Sarcoidosis can occur with SLE. It is unclear if anti-dsDNA antibodies in patients with sarcoidosis signify the eventual development of SLE. OBJECTIVES: To determine the prevalence of anti-dsDNA antibodies in patients with sarcoidosis in a university hospital and their significance in predicting the diagnosis of associated SLE. METHODS: In a retrospective study, 34 patient files with diagnosed sarcoidosis in a university hospital during a period of 15 years were reviewed for serological markers, including ANA, anti-dsDNA, and immunoglobulin and C3 levels. The occurrence of SLE in these patients also was evaluated. RESULTS: ANA were positive in 10 of 34 of the patients screened. Two patients with sarcoidosis had antibodies to dsDNA. C3 levels in these 34 patients were an average of 87.7 +/- 25.3 mg/100 mL, which is within the normal range. IgG immunoglobulin levels were an average of 2,206 +/- 999 mg/100 mL, which was above normal limits. The 2 patients who were positive for anti-dsDNA had normal C3 levels and SLE did not develop during a follow-up period of 10 to 15 years. CONCLUSIONS: Anti-dsDNA antibodies may occur in patients with sarcoidosis, but their presence does not predict the subsequent development of SLE. CAS Registry/EC Number 0 (Antibodies, Antinuclear). 0 (Complement 3). 0 (Immunoglobulin G). 9007-49-2 (DNA).

RELAPSES / EXACERBATIONS OF SLE.....

<7>

Unique Identifier:9462168

Authors: Bootsma H. Spronk PE. Ter Borg EJ. Hummel EJ. de Boer G. Limburg PC. Kallenberg CG.

Institution: Department of Internal Medicine, University Hospital Groningen, The Netherlands.

Title: The predictive value of fluctuations in IgM and IgG class anti-dsDNA antibodies for relapses in systemic lupus erythematosus. A prospective long-term observation.

Source: Annals of the Rheumatic Diseases. 56(11):661-6, 1997 Nov.

Abstract: OBJECTIVE: This study investigated the predictive value of rises in IgM class antibodies against double stranded DNA (anti-dsDNA) for ensuing relapses in systemic lupus erythematosus (SLE) in comparison with rises in IgG class antibodies. In addition, it was analysed whether rises in IgM class anti-dsDNA were associated with specific clinical manifestations of SLE. METHODS: Thirty four of a cohort of 72 SLE patients who were positive for IgM class anti-dsDNA at the start of the study or at the time of a relapse were analysed monthly for class specific anti-dsDNA levels during a median observation period of 19.6 months. Disease activity was scored according to the SLE Disease Activity Index. Anti-dsDNA were measured by IgM and IgG class enzyme linked immunosorbent assay (ELISA) and by Farr assay. RESULTS: During the study 18 of 34 patients experienced 26 relapses. Twenty two (85%) of the relapses were accompanied by a positive test for IgM class anti-dsDNA by ELISA, 23 (89%) were positive for IgG class anti-dsDNA by ELISA, and 25 (96%) were positive by Farr assay. Patients with rises in IgG class anti-dsDNA by ELISA or in anti-dsDNA by Farr assay had a significantly higher cumulative risk for relapses than patients without those increases (p = 0.04 and p = 0.03, respectively). This was not the case for rises in IgM class anti-dsDNA (p = 0.16). Moreover, a rise in IgM class anti-dsDNA before a relapse was not associated, expressed in terms of odds ratios, with specific clinical manifestations of SLE. CONCLUSION: Relapses of SLE are frequently accompanied by IgM class anti-dsDNA. Rises of IgM class anti-dsDNA, in contrast with rises in IgG class anti-dsDNA, are not a sensitive tool for predicting a relapse and are not associated with specific clinical manifestations of SLE. CAS Registry/EC Number 0 (Antibodies, Antinuclear). 0 (Immunoglobulin G). 0 (Immunoglobulin M).

<10>

Unique Identifier:2346519

Authors: ter Borg EJ. Horst G. Hummel EJ. Limburg PC. Kallenberg CG.

Institution: Department of Internal Medicine, University Hospital, Groningen, The Netherlands.

Title: Measurement of increases in anti-double-stranded DNA antibody levels as a predictor of disease exacerbation in systemic lupus erythematosus. A long-term, prospective study.

Source: Arthritis & Rheumatism. 33(5):634-43, 1990 May.

Abstract: To evaluate the predictive power of changes in levels of antibodies to double-stranded DNA (anti-dsDNA) as a predictor of disease exacerbations in systemic lupus erythematosus (SLE), we performed a prospective study on 72 unselected patients with SLE (mean duration of study 18.5 months, range 6-35 months). Patients were seen at least once every 3 months, and disease activity was scored according to a specific protocol. Plasma samples were obtained at least once every month and were assessed for anti-dsDNA antibody (by the Crithidia luciliae assay, an enzyme-linked immunosorbent assay [ELISA], and the Farr assay) and for complement components C3 and C4. Twenty-seven of 33 disease exacerbations observed during the study period were accompanied by a positive test result for anti-dsDNA antibody (27 by the Farr assay, 19 by the C luciliae assay, and 23 by the ELISA). Twenty-four of these exacerbations were preceded by a significant increase in anti-dsDNA antibody levels (23 by the Farr assay, 12 by the C luciliae assay, and 17 by the ELISA). The first observance of a significant increase in anti-dsDNA antibody levels preceded the exacerbation by 8-10 weeks. Significant increases in anti-dsDNA antibody levels not followed by an exacerbation were observed in 5 cases by the Farr assay, in 7 cases by the C luciliae assay, and in 3 cases by the ELISA; however, in 3 cases, 2 cases, and 1 case, respectively, these increases were followed by an increase in disease activity that did not fulfill the criteria for an exacerbation. Serial measurement of anti-dsDNA antibody levels was more sensitive for predicting exacerbations than was measurement of C3 and/or C4 levels (P less than 0.03). Serial assessment of anti-dsDNA antibody levels, especially by the Farr assay, is a sensitive and reasonably specific method for predicting disease exacerbations in SLE. CAS Registry/EC Number 0 (Antibodies, Antinuclear). 0 (Complement 3). 0 (Complement 4). 9007-49-2 (DNA).

<14>

Unique Identifier:3487292

Authors: Swaak AJ. Groenwold J. Bronsveld W.

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

Source: Annals of the Rheumatic Diseases. 45(5):359-66, 1986 May.

Abstract: 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. CAS Registry/EC Number 0 (Antibodies, Antinuclear). 9007-36-7 (Complement). 9007-49-2 (DNA).