Abstract
ObjectivesTo evaluate the role of serum IgG, IgM and IgA anti-dsDNA antibody isotypes in the diagnosis of systemic lupus erythematosus (SLE), and their association with clinical features and disease activity, in a large cohort of SLE patients.MethodsSera of 200 SLE patients (mean age 34±10.3 years; 26 male and 174 female; median duration of disease 115 months, range 7–378), and of 206 controls, including 19 Sjögren's syndrome, 27 rheumatoid arthritis, 26 psoriatic arthritis, 15 idiopathic inflammatory myopathies (IIM), 13 systemic sclerosis, 49 infectious diseases and 57 healthy subjects, were tested for anti-dsDNA IgG, IgM and IgA isotypes.ResultsSelecting a cutoff corresponding to 95% specificity, the sensitivity of IgG, IgM and IgA anti-dsDNA antibodies in SLE was 55%, 30% and 49%, respectively; 12.5%, 1% and 7.5% of SLE patients had positive IgG, IgM or IgA isotype alone, respectively. SLE patients with glomerulonephritis showed higher levels of IgA anti-dsDNA (p = 0.0002), anti-dsDNA IgG/IgM (p = 0.001) and IgA/IgM (p<0.0001) ratios than patients without renal disease. No significant associations have been found between anti-dsDNA isotypes and other clinical features. IgA anti-dsDNA (p = 0.01) (but not IgG or IgM) and IgG/IgM ratio (p = 0.005) were significantly higher in patients with more active disease (ECLAM score >4).ConclusionsThe detection of IgA anti-dsDNA autoantibodies seems to improve our ability to diagnose SLE and to define lupus nephritis phenotype and active disease. By contrast, IgM anti-dsDNA antibodies might be protective for renal involvement. These data support the hypothesis that anti-dsDNA antibody class clustering may help to refine SLE diagnosis and prognosis.
Highlights
Anti-double stranded DNA antibodies are a useful tool for the diagnosis of systemic lupus erythematosus (SLE) [1,2] and represent one of the criteria of the American College of Rheumatology (ACR) for the classification of SLE
Global SLE activity was measured by the European Consensus Lupus Activity Measure (ECLAM) score [24], and the classification of lupus glomerulonephritis was based on the International Society of Nephrology/Renal Pathology Society (ISN/RPS 2003) classification [25]
Considering all three antibody classes, the sensitivity increases to 67%, but the specificity decreases to 90.7%
Summary
Anti-double stranded DNA (anti-dsDNA) antibodies are a useful tool for the diagnosis of systemic lupus erythematosus (SLE) [1,2] and represent one of the criteria of the American College of Rheumatology (ACR) for the classification of SLE. Several studies have shown a correlation between disease activity and anti-dsDNA antibody levels in SLE, in patients with renal involvement [3,4,5,6,7], making detection of such antibodies relevant in SLE monitoring [8]. IgG-class anti-dsDNA have been implicated in the pathogenesis of organ manifestation of SLE, glomerulonephritis, as shown in murine models, where the transfer of murine monoclonal IgG antibodies or anti-dsDNA producing hybridomas into mice induces lupus-like glomerulonephritis [10,11]
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