Low diagnostic and predictive value of anti-dsDNA antibodies in unselected patients with recent onset of rheumatic symptoms: results from a long-term follow-up Scandinavian multicentre study

Compagno, Michele; Jacobsen, Søren; Rekvig, Ole Petter; Truedsson, Lennart; Heegaard, Niels H. H.; Nossent, Jiri; Jönsen, Andreas; Jacobsen, Rasmus Sleimann; Eilertsen, Gro Østli; Sturfelt, Gunnar; Bengtsson, Anders

doi:10.3109/03009742.2013.765032

Cited by 28 publications

(21 citation statements)

References 16 publications

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“…The presence of anti‐dsDNA in ANA‐negative SLE patients has been reported by others . These patients were reported to have more severe complications, including nephritis , dystrophic calcification , or severe autoimmune neutropenia .…”

Section: Discussionsupporting

confidence: 56%

Antinuclear Antibody–Negative Systemic Lupus Erythematosus in an International Inception Cohort

Choi

Clarke

Pierre

et al. 2019

Arthritis Care & Research

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Section: Discussionsupporting

confidence: 56%

Antinuclear Antibody–Negative Systemic Lupus Erythematosus in an International Inception Cohort

Choi

Clarke

Pierre

et al. 2019

Arthritis Care & Research

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“…We previously observed a sensitivity of 81% for anti-chromatin and 96% for anti-dsDNA in the same cohort of SLE patients with nephritis [29]. Other studies reported different sensitivities and specificities for anti-chromatin (ranging from 45–100% and 88–100%, respectively), and for anti-dsDNA assays (ranging from 35–74% and 79–100%, respectively) [2, 33–35]. The specificity of anti-histone autoantibodies for SLE is still under debate, and the observed prevalence (<50%) in SLE patients is always lower compared to anti-dsDNA and anti-chromatin reactivity [36,37], as we have previously described [29].…”

Section: Discussionmentioning

confidence: 92%

Autoantibodies against Modified Histone Peptides in SLE Patients Are Associated with Disease Activity and Lupus Nephritis

et al. 2016

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Persistent exposure of the immune system to death cell debris leads to autoantibodies against chromatin in patients with systemic lupus erythematosus (SLE). Deposition of anti-chromatin/chromatin complexes can instigate inflammation in multiple organs including the kidney. Previously we identified specific cell death-associated histone modifications as targets of autoantibodies in SLE. In this study we addressed, in a large cohort of SLE patients and controls, the question whether plasma reactivities with specific histone peptides associated with serology and clinical features. Plasma from SLE patients with and without lupus nephritis, disease controls, and healthy controls, were tested in ELISA with histone H4 peptide acetylated at lysines 8, 12 and 16 (H4pac), H2B peptide acetylated at lysine 12 (H2Bpac), H3 peptide trimethylated at lysine 27 (H3pme), and their unmodified equivalents. SLE patients displayed a higher reactivity with the modified equivalent of each peptide. Reactivity with H4pac showed both a high sensitivity (89%) and specificity (91%) for SLE, while H2Bpac exhibited a high specificity (96%) but lower sensitivity (69%). Reactivity with H3pme appeared not specific for SLE. Anti-H4pac and anti-H2Bpac reactivity demonstrated a high correlation with disease activity. Moreover, patients reacting with multiple modified histone peptides exhibited higher SLEDAI and lower C3 levels. SLE patients with renal involvement showed higher reactivity with H2B/H2Bpac and a more pronounced reactivity with the modified equivalent of H3pme and H2Bpac. In conclusion, reactivity with H4pac and H2Bpac is specific for SLE patients and correlates with disease activity, whereas reactivity with H2Bpac is in particular associated with lupus nephritis.

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“…To this end, it is noteworthy that even the CLIFT test, which according to the present results is the anti-dsDNA assay best correlated with a typical nephritic SLE phenotype, had only low diagnostic value in the diagnosis of SLE in this population of patients with recent onset of rheumatic symptoms. 55 When analysing the ANA-positive subset of the patients, the CLIFT association with clinical phenotypes consisting of proteinuria, haematuria, leukopenia, thrombocytopenia, cutaneous vasculitis and alopecia persisted. On the other hand, pleuritis and proteinuria defined the clinical phenotypes associated with any of the anti-dsDNA tests in ANA-negative patients.…”

Section: Discussionmentioning

confidence: 98%

Clinical phenotype associations with various types of anti-dsDNA antibodies in patients with recent onset of rheumatic symptoms. Results from a multicentre observational study

et al. 2014

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Despite anti-dsDNA antibodies constitute a wide range of specificities, they are considered as the hallmark for systemic lupus erythematosus (SLE).ObjectiveTo identify clinical phenotypes associated with anti-dsDNA antibodies, independently of any clinical diagnoses.MethodsPatients with recent onset of any rheumatic symptoms were screened for antinuclear antibodies (ANA). All ANA-positive and matching ANA-negative patients were examined, and their clinical phenotypes were registered, using a systematic chart formulated after consensus between the participating centres. All patients were tested for different anti-dsDNA antibody specificities with assays habitually used in each participating laboratory. Crithidia Luciliae Immuno Fluorescence Test (CLIFT) was performed three times (with two different commercial kits); solid and solution phase ELISA were performed four times. Associations between clinical phenotypes and results of anti-dsDNA assays were evaluated by linear regression analysis (LRA) and principal component analysis (PCA).ResultsTotally, 292 ANA-positive and 292 matching ANA-negative patients were included in the study. A full dataset for statistical analysis was obtained in 547 patients. Anti-dsDNA antibodies were most frequently detected by ELISA. LRA showed that overall positivity of anti-dsDNA antibodies was associated with proteinuria and pleuritis. Alopecia was significantly associated only with CLIFT-positivity. Besides confirming the same findings, PCA showed that combined positivity of CLIFT and ELISA was also associated with lymphopenia.ConclusionsOur results show that different anti-dsDNA antibody specificities are associated with nephropathy, pleuritis, alopecia and lymphopenia, regardless of the diagnosis. It may challenge the importance of anti-dsDNA antibodies as a diagnostic hallmark for SLE.

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Low diagnostic and predictive value of anti-dsDNA antibodies in unselected patients with recent onset of rheumatic symptoms: results from a long-term follow-up Scandinavian multicentre study

Cited by 28 publications

References 16 publications

Antinuclear Antibody–Negative Systemic Lupus Erythematosus in an International Inception Cohort

Antinuclear Antibody–Negative Systemic Lupus Erythematosus in an International Inception Cohort

Autoantibodies against Modified Histone Peptides in SLE Patients Are Associated with Disease Activity and Lupus Nephritis

Clinical phenotype associations with various types of anti-dsDNA antibodies in patients with recent onset of rheumatic symptoms. Results from a multicentre observational study

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