The impact of biological treatments on the anti-dsDNA and anti-nucleosome tests

• Published in: Lupus 2018-01, Vol.27 (1), p.40-48
• Main Authors: Infantino, M, Grossi, V, Benucci, M, Li Gobbi, F, Damiani, A, Manfredi, M
• Format: Article
• Language: English
• Subjects: Anti-DNA antibodies; Antibodies, Antinuclear - blood; Antirheumatic Agents - adverse effects; Arthritis; Arthritis - drug therapy; Arthritis - immunology; Autoantibodies; Biological products; Biomarkers - blood; Cell Line; Deoxyribonucleic acid; DNA; Fluorescent Antibody Technique; Genetic testing; Humans; Immunoglobulins; Lupus; Lupus Erythematosus, Systemic - chemically induced; Lupus Erythematosus, Systemic - immunology; Retrospective Studies; Systemic lupus erythematosus
• ISSN: 0961-2033; 1477-0962
• DOI: 10.1177/0961203317709344

Background Anti-double stranded DNA antibodies are a very heterogeneous group of antibodies, quite specific for systemic lupus erythematosus. Newer technologies, such as addressable laser bead immunoassays (ALBIA), show great potential as a diagnostic application. The production of anti-double stranded DNA antibodies is often encountered in inflammatory arthritis; however, literature reports that the actual onset of drug induced lupus in patients treated with biological drugs is a rare event. False positive results for anti-double stranded DNA and anti-nucleosome antibodies detected in patients with inflammatory arthritis treated with different biologics prompted the investigation of full autoantibody profiles to evaluate each biomarker’s diagnostic performance in systemic lupus erythematosus. The aim of the study was to compare the diagnostic performance of anti-double stranded DNA antibody and anti-nucleosome antibody methods and to evaluate the value of simultaneously measuring anti-double stranded DNA and anti-nucleosome antibodies, along with other anti-nuclear antibody analytes, as biomarkers for systemic lupus erythematosus, using a more appropriate control cohort including inflammatory arthritis patients with a non-clinical drug induced lupus. Methods Anti-double stranded DNA and anti-nucleosome antibody levels were evaluated in 247 patient samples: 70 systemic lupus erythematosus, 177 disease controls (including 97 inflammatory arthritis during treatment with different biologics) using the Bio-Rad BioPlex® 2200. Results Anti-nucleosome antibodies demonstrated greater clinical sensitivity and specificity than anti-double stranded DNA antibodies. At the manufacturers’ cut-off range, considering the two markers as a single or combined test, the “anti-double stranded DNA test or anti-nucleosome antibodies” was the most sensitive combination (0.400) with the best negative likelihood ratio (0.62) and negative predictive value (0.803). Conclusion Anti-nucleosome antibodies are a more sensitive and specific biomarker of systemic lupus erythematosus than anti-double stranded DNA antibodies. Anti-nucleosome antibodies and anti-double stranded DNA antibodies are independent and complementary markers of systemic lupus erythematosus diagnosis and, therefore, are strongly suggested as combined tests (positive predictive value = 0.938). Moreover, the combined use of the two tests may help to overcome the decreased specificity percentage of the anti-double strand