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Table 1 Predictivity of anti-dsDNA antibodies in SLE flares

From: Predictive biological markers of systemic lupus erythematosus flares: a systematic literature review

Assay

Number of patients (n)

Findings

Study

Positive results

 CLIF

61

67% of patients in the group with exacerbations had persistent anti-dsDNA ab versus 27% in the patient group without exacerbations

Oelzner et al., 1996 [14]

 CLIF

299

Increased level at baseline was a risk factor for flare in the haematological system (p = 0.003)

Petri et al., 2009 [10]

 CLIF

65

Cases, defined as experiencing a surge in anti-dsDNA from 0 to 3+/4+, or from 1+ to 4+, within a period of less than 12 months, were more likely to experience a severe flare than controls (OR 6.3 (CI 2.0–19.9), p = 0.02)

Pan et al., 2014 [25]

 Farr

487

Frequency of renal flare was lower in patients with sustained reductions in anti-dsDNA ab (> 10% from baseline levels for at least 2/3 of all observed values) than in patients with stable or increasing antibody levels

Linnik et al., 2005 [24]

 Farr

130

All 15 major exacerbations were preceded by an increase of the anti-dsDNA ab levels, with a doubling time of less than 6 weeks for 13 patients. There were four other patients with an increase in anti-dsDNA levels who did not show any exacerbation

Swaak et al., 1982 [11]

 Farr

143

A continuous increase in the anti-dsDNA ab was found for all patients in the 24 weeks preceding exacerbations with a doubling time < 10 weeks

Swaak et al., 1986 [12]

 Farr

78

A sharp drop in anti-dsDNA ab, usually preceded by a rise, was related to a serious exacerbation

Swaak et al., 1979 [4]

 Farr

151

Anti-dsDNA increase started 4 months prior to the relapse and reached a maximum at the moment of relapse whereas no fluctuations were observed in patients with persistently inactive disease

Coremans et al., 1995 [15]

 Farr

23

Presence of anti-dsDNA abs (> 5 IU/ml) or increase (> 25%) was associated with a high risk of renal flare

Matrat et al., 2011 [29]

 Farr

199

Patients with anti-dsDNA ab (> 15 IU/ml) had a greater risk of developing proliferative glomerulonephritis than patients without auto-antibodies (p = 0.048)

Cortés-Hernàndez et al., 2004 [22]

 ELISA

70

Anti-dsDNA antibodies were detected in 14 (93.3%) of 15 patients with subsequent lupus nephritis, compared with 24 (72.7%) of 33 patients with active SLE and no nephritis (p = ns) and nine (73%) patients with inactive SLE and no nephritis (p = ns). Sensitivity for severe lupus nephritis was 100%

Meyer et al., 2009 [30]

 Farr and EliA

48

All 22 exacerbations were accompanied by changes in anti-dsDNA (> 25%) in one or both assays

Hillebrand et al., 2013 [26]

 CLIF and ELISA

53

Increase in anti-dsDNA ab predicted flares with M-SLEDAI and M-LAI indices

Ho et al., 2001 [17]

 CLIF, ELISA and Farr

72

89% of the exacerbations were preceded by a significant increase in anti-dsDNA ab levels (defined as ≥ 2 titres by the C. luciliae test or ≥ 25% and at least 100 IU/ml by the ELISA or ≥ 25% and at least 30 IU/ml by the Farr assay)

ter Borg et al., 1990 [13]

 ELISA and Farr

34

Patients with rises in IgG class anti-dsDNA ab by ELISA (≥ 6 IU/ml) or in anti-dsDNA by Farr assay (≥ 15 IU/ml) had a significantly higher cumulative risk for relapses, with a median time of 2.3 and 2.1 months respectively

Bootsma et al., 1997 [16]

 NA

189

Persistently positive anti-dsDNA after cyclophosphamide treatment was an independent predictor of renal flares

Mok et al., 2004 [23]

 NA

218

The combination of complement C3, C4 and anti-dsDNA antibody is reasonably specific for predicting lupus flares in the preceding 4 weeks

To et al., 2011 [28]

 NA

562

Elevated titres (≥ 200 IU/ml) at baseline were independent predictors of moderate-to-severe flares at week 52

Petri et al., 2013 [9]

Negative results

 CLIF

27

Serial measurements of anti-dsDNA ab were poor markers of exacerbation.

Lloyd and Schur, 1981 [19]

 Farr

48

Changes in anti-dsDNA ab failed to correctly predict a change in disease activity

Abrass et al., 1980 [18]

 Farr

202

Fluctuations in anti-dsDNA ab were poor predictors of disease exacerbations according to SLEDAI

Esdaile et al., 1996 [20]

 Farr

120

No consistent association between anti-dsDNA ab positivity and risk of flare defined by SLEDAI

Mirzayan et al., 2000 [6]

 Farr

46

Baseline anti-dsDNA ab failed to predict renal relapses

El Hachmi et al., 2003 [8]

 ELISA

23

Anti-dsDNA ab were not predictive of flare

Steiman et al., 2010 [21]

 Farr and CLIF

73

No difference between the patients who flared and the patients who did not

Walz LeBlanc et al., 1994 [31]

 NA

57

Percentage of patients who had positive anti-dsDNA ab at the time of the diagnosis was not higher in patients with a subsequent exacerbation

Tomioka et al., 2008 [7]

 NA

110

Anti-dsDNA ab were not identified as a predictor of flare

Swaak et al., 1989 [5]

 NA

218

Anti-dsDNA lacks sensitivity in predicting serosal and neuropsychiatric lupus flares

To et al., 2011 [27]

  1. anti-dsDNA ab anti-double-stranded DNA antibodies, CI confidence interval, CLIF Crithidia luciliae immunofluorescence, ELISA enzyme-linked immunosorbent assay, EliA automated enzyme fluoroimmunoassay, M-LAI Modified Lupus Activity Index, M-SLEDAI Modified Systemic Lupus Erythematosus Disease Activity Index, NA not available, ns not significant, OR odds ratio, SLE systemic lupus erythematosus, SLEDAI Systemic Lupus Erythematosus Disease Activity Index