A total of 38 patients (3 male and 35 female, of whom 37 fulfilled four and one fulfilled only three of the American College of Rheumatology (ACR) criteria for SLE [17,18]) were identified as having donated blood before the onset of any symptoms of disease. Biobank register (Ume?, Sweden). Antibodies against anti-Sj?gren’s syndrome antigen A (Ro/SSA; 52 and 60 kDa), anti-Sj?gren’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 1:100. Results Autoantibodies 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 quantity of autoantibodies in prediseased individuals was 1.4, and after disease onset it was 3.1 ( em P /em 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. Conclusions Autoantibodies 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. Introduction Systemic lupus erythematosus (SLE) is usually a heterogeneous disease with diverse clinical manifestations and variable severity in individual patients and between different patient populations [1,2]. A typical pathophysiological sign in SLE patients is the production of autoantibodies directed against nuclear antigens, which precede the development of clinical manifestations [3,4]. In particular, antibodies against double-stranded DNA (anti-dsDNA) have been shown to increase just prior to a diagnosis of SLE . Individuals who develop SLE have also been found to gradually fulfill the clinical classification criteria that are preceded by the appearance of associated autoantibodies before diagnosis . Furthermore, in patients defined as having undifferentiated connective tissue disease, a diagnosis of SLE was predicted in a 5-12 months follow-up study on the basis of the presence of anti-dsDNA antibodies . There are several autoimmune diseases that are recognised by exhibiting a long preclinical phase during which susceptible BA-53038B individuals who later develop disease can be identified by the presence of autoantibodies [8-11]. The development of a rheumatic disease in asymptomatic mothers expressing anti-Sj?gren’s syndrome antigen A (Ro/SSA) and/or anti-Sj?gren’s syndrome antigen B (La/SSB) antibodies, and identified by the birth of a child with a congenital heart block, was found to be relatively common at 48% . In another study, the detection Rabbit polyclonal to CD24 (Biotin) of anti-La/SSB antibodies predated clinical evidence of Sj?gren’s syndrome by months and in some cases by years . Furthermore, in an animal model of SLE, mice immunized with human Ro/SSA developed autoimmunity not only towards this molecule but also towards other immunologically similar molecules in a process equivalent to epitope spreading . The presence of antinuclear antibodies (ANAs) was shown to predate the development of SLE in a small study conducted in Finland . In the study by Arbuckle em et al. /em , the frequency of producing at least one SLE-related autoantibody years before BA-53038B diagnosis was high at 88%. ANAs were present in 78% of the cases, anti-dsDNA antibodies were present in 55% and anti-Ro/SSA antibodies were present in 47%. Furthermore, the appearance of these antibodies appeared to follow a predictable BA-53038B course . Anticardiolipin antibodies have been found to precede both the diagnosis of SLE and the development of clinical manifestations of thrombosis by a number of years . The aim of this study was to analyse, using multiplex technology, the autoantibodies predating the onset of symptoms of SLE in individuals in a patient population in northern Europe and to relate these autoantibodies to BA-53038B the first recorded symptom of disease. Materials and methods Patients and controls The register of patients with SLE attending the Department of Rheumatology, University Hospital, Ume?, Sweden, with a known date of the BA-53038B onset of symptoms was coanalysed with the registers of the Medical Biobank (Ume?, Sweden) and of the maternity cohort (that is, the record of samples obtained for rubella screening of pregnant women) from northern Sweden. All SLE patients had been evaluated clinically. A total of 38 patients (3.