Anti-topoisomerase-I antibodies in systemic lupus erythematosus and potential association with the presence of anti-dsDNA antibodies

Sir, Anti-topoisomerase I antibody (Scl-70) targets a DNA-linked protein and is considered a specific marker for systemic sclerosis (SSc). Some case reports and a cohort study reported the occurrence of Scl-70 in up to 25% of patients with systemic lupus erythematosus (SLE), with a great variability related to the different methods employed, antigen source or cut-off levels. Scl-70 detected in SLE sera seem to recognize different epitopes (located in a region between aminoacids 300 and 400) compared with epitopes specific for Scl-70 in SSc. In addition, antibody titres are usually far higher in SSc than in SLE. The purpose of this work is to analyse the prevalence of Scl-70 in SLE with a highly sensitive method (such as CLIA) and to correlate Scl-70 positive sera with peculiar clinical and serological features. We collected 170 sera: 130 SLE and 40 controls (20 Raynaud’s without the criteria for SSc, 10 SSc and 10 healthy subjects). The SLE group was composed of 95% Caucasian patients, 93% female, with a low disease activity at the moment of evaluation (mean SLEDAI-2K: 2.68, standard deviation (SD): 2.6). They showed arthritis in 27%, malar rash in 50%, subacute cutaneous lupus in 10%, glomerulonephritis in 36%, serositis in 13% and cytopenia in 45% of cases. All sera were tested for anti-ENA, including Scl70, with counter-immunoelectrophoresis (CIE); for Scl-70, anti-dsDNA and anti-chromatine antibodies with CLIA BioFlash (IL diagnostics, San Diego, CA). Antibodies to dsDNA were also tested by a radioimmunoassay (RIA, Farr assay; Kodak). BioFlash CLIA showed an overall sensitivity and specificity of 83%–100% and 94%–99%, respectively, for anti-ENA detection, while sensitivity and specificity of 36% and 98,7%, respectively, was reported for anti-Scl70, using Baculovirusrecombinant Scl-70 antigen. Cohen k test was performed to compare the agreement of CLIA and CIE. Anti-Scl-70 was detected in 10/170 sera (5.9%) by CLIA and in 6/170 sera (3.5%) by CIE. In particular, six sera were CLIA Scl-70þ/CIE Scl-70þ, while four sera were CLIA Scl-70þ/CIE Scl-70-; Cohen k analysis reported a good agreement (k1⁄4 0.73). The 6 CLIA Scl-70þ/CIE Scl-70þ were all SSc patients, therefore analysing only SSc patients, the agreement was perfect (k1⁄4 1). No CLIA Scl-70þ/CIE Scl-70þ was found in SLE (k1⁄4 0, no agreement). AntiScl-70 were found by CLIA in 3/130 SLE (2.3%). Only four sera were discordant (Scl70þ by CLIA, negative by CIE): clinical and demographic features of these patients (three SLE and one Raynaud’s phenomenon) are reported in Table 1. Interestingly, only one out of the three patients developed a clinical picture resembling SSc, even though not classifiable as SSc. In SLE, Scl-70 are detected in 2.3% of sera by a very sensitive CLIA, but none was positive by CIE. We previously reported that CIE was far less sensitive than CLIA, detecting only three Scl-70 in a cohort of 540 SLE (0.55%). Nonetheless we found a perfect agreement between the two assays for SSc and a very good agreement when other controls were tested. The three Scl-70 positive SLE sera were all antidsDNA and anti-chromatin positive thus confirming the relationship between anti-DNA and DNA binding protein such as topoisomerase-I. We therefore conclude that further studies are needed to evaluate their clinical significance, and can predict overlap between SSc and SLE.