Autoantibodies predate the onset of systemic lupus erythematosus in northern Sweden

Abstract

IntroductionAutoantibodies have a central role in systemic lupus erythematosus (SLE). The presence of autoantibodies preceding disease onset by years has been reported both in patients with SLE and in those with rheumatoid arthritis, suggesting a gradual development of these diseases. Therefore, we sought to identify autoantibodies in a northern European population predating the onset of symptoms of SLE and their relationship to presenting symptoms.MethodsThe register of patients fulfilling the American College of Rheumatology criteria for SLE and with a given date of the onset of symptoms was coanalysed with the register of the Medical Biobank, Umeå, Sweden. Thirty-eight patients were identified as having donated blood samples prior to symptom onset. A nested case-control study (1:4) was performed with 152 age- and sex-matched controls identified from within the Medical Biobank register (Umeå, Sweden). Antibodies against anti-Sjögren's syndrome antigen A (Ro/SSA; 52 and 60 kDa), anti-Sjögren's syndrome antigen B, anti-Smith antibody, ribonucleoprotein, scleroderma, anti-histidyl-tRNA synthetase antibody, double-stranded DNA (dsDNA), centromere protein B and histones were analysed using the AtheNA Multi-Lyte ANA II Plus Test System on a Bio-Plex Array Reader (Luminex200). Antinuclear antibodies test II (ANA II) results were analysed using indirect immunofluorescence on human epidermal 2 cells at a sample dilution of 1:100.ResultsAutoantibodies against nuclear antigens were detected a mean (±SD) of 5.6 ± 4.7 years before the onset of symptoms and 8.7 ± 5.6 years before diagnosis in 63% of the individuals who subsequently developed SLE. The sensitivity (45.7%) was highest for ANA II, with a specificity of 95%, followed by anti-dsDNA and anti-Ro/SSA antibodies, both with sensitivities of 20.0% at specificities of 98.7% and 97.4%, respectively. The odds ratios (ORs) for predicting disease were 18.13 for anti-dsDNA (95% confidence interval (95% CI), 3.58 to 91.84) and 11.5 (95% CI, 4.54 to 28.87) for ANA. Anti-Ro/SSA antibodies appeared first at a mean of 6.6 ± 2.5 years prior to symptom onset. The mean number of autoantibodies in prediseased individuals was 1.4, and after disease onset it was 3.1 (P < 0.0005). The time predating disease was shorter and the number of autoantibodies was greater in those individuals with serositis as a presenting symptom in comparison to those with arthritis and skin manifestations as the presenting symptoms.ConclusionsAutoantibodies against nuclear antigens were detected in individuals who developed SLE several years before the onset of symptoms and diagnosis. The most sensitive autoantibodies were ANA, Ro/SSA and dsDNA, with the highest predictive OR being for anti-dsDNA antibodies. The first autoantibodies detected were anti-Ro/SSA.

What to Expect When Expecting With Systemic Lupus Erythematosus (SLE): A Population‐Based Study of Maternal and Fetal Outcomes in SLE and Pre‐SLE

“…Whether systemic immune alterations pre‐dating disease have an effect on pregnancy is not known. Autoantibodies associated with SLE, including antiphospholipid antibodies and SSA, both of which are known to be associated with pregnancy morbidity, are present up to 5 years before the clinical diagnosis of SLE 4, 5, 6. Furthermore, as the clinical diagnosis nears, the levels of many of these autoantibodies increase 4.…”

Choosing Wisely: The Canadian Rheumatology Association’s List of 5 Items Physicians and Patients Should Question

“…Autoantibodies can precede the full clinical expression of an underlying disease for many years 18,19 , and atypical clinical presentations of CTD can occur. Thus, clinical judgment should guide ANA testing in these cases 11 .…”

Frequency of anti-nuclear antibody and anti dsDNA antibodies in subjects of oral addictive habits

“…19 A study conducted in Northern Sweden, reported that autoantibodies can be detected in the serum of individuals who develop systemic lupus erythematosus several years before the appearance of clinical signs and symptoms. 20 Considering the association of different oral addictive habits with the development of autoimmune diseases, some researchers have reported that smoking protects against production of antithyroid peroxidase antibodies.…”