Clinical and serological associations of autoantibodies to the Ku70/Ku80 heterodimer determined by a novel chemiluminescent immunoassay

Abstract

Background: Autoantibodies targeting Ku, an abundant nuclear protein with DNA helicase activity, have been reported in patients with systemic autoimmune rheumatic diseases. Little is known about the clinical associations of anti-Ku antibodies, especially when novel diagnostic technologies are used. The objective of the present study was to analyse the prevalence of antiKu antibodies in different medical conditions using a novel chemiluminescent immunoassay. Patients and methods: Serum samples from adult patients with systemic lupus erythematosus (SLE, n¼305), systemic sclerosis (SSc, n¼70) and autoimmune myositis patients (AIM, n¼109) were the primary focus of the study. Results were compared with disease controls (rheumatoid arthritis, RA, n¼30; infectious diseases, n¼17) and healthy individuals (n¼167). In addition, samples submitted for routine autoantibody testing from patients referred to a rheumatology clinic (n¼1078) were studied. All samples were tested for anti-Ku antibodies by QUANTA Flash Ku chemiluminescent immunoassay (research use only, Inova Diagnostics, San Diego, USA) using full length recombinant human Ku. SLE patient samples were also tested for other autoantibodies. Clinical data of anti-Ku antibody positive patients (high titres) were obtained by retrospective chart review. Results and findings: In the disease cohorts, 30/305 (9.8%) SLE, 3/70 (4.3%) systemic sclerosis and 4/109 (3.7%) autoimmune myositis (AIM) patients were positive, respectively. The four positive AIM patients had an overlap myositis syndrome that included two patients with SLE. The three systemic sclerosis (SSc) positive samples had diagnoses of SSc/SLE overlap, diffuse cutaneous SSc, and early edematous phase SSc. In the control cohorts, 2/170 (1.2%) healthy individuals (all low titre), 0/30 (0.0%) (RA) and 0/17 (0.0%) infectious disease patients were positive. The area under the curve values were: 0.75 for SLE vs. controls, 0.68 for SSc vs. controls and 0.37 for AIM vs. controls. In the rheumatology clinic referral cohort, 12/1078 (1.1%) were positive for anti-Ku antibodies, nine showing low and three high titres. The diagnoses of the three high positive anti-Ku positive patients were: probable SLE, mixed connective tissue disease (MCTD) and ANA positive RA. Conclusion: Anti-Ku antibodies detected by chemiluminescent immunoassay are most prevalent in SLE. When found in AIM and SSc, they were associated with overlap syndrome and early SSc. Lupus (2016) 25, 889-896.

Overlap of systemic lupus erythematosus and myositis is rare in anti-Ku antibody-positive patients

“…Thus, anti-dsDNA positivity and SLE were mutually exclusive in the present anti-Ku-positive patients. In contrast, a previous international study compared the clinical and laboratory characteristics of 22 anti-Ku-positive SLE patients with those of 209 anti-Ku-negative SLE patients 5. In both anti-Ku-positive and anti-Ku-negative SLE groups, frequencies of anti-dsDNA were similar: 31.8% and 32.2%, respectively.…”

“…This discrepancy might be due to a difference of genetic backgrounds. Since anti-dsDNA are not so frequently found (around 30%) in anti-Ku-positive SLE5 in addition to the presence of anti-dsDNA in ‘anti-Ku with elevated CK patients’ in our study, we might have to be careful in using the results of anti-dsDNA for differential diagnosis. We also found anti-ssDNA in 9 of the 10 anti-Ku-positive patients in the present study.…”

Anti-Ku antibodies: important points to consider

“…Therefore, the conclusion that overlap syndrome in anti-Ku-positive patients is rare might not reflect the entire picture. In our experience, anti-Ku antibodies are frequently found in SLE patients potentially associated with overlap features of a myopathy 10. Similarly, anti-Ku antibodies are known as autoantibodies that mark the overlap between myositis and systemic sclerosis 11…”

Two-Parametric Immunological Score Development for Assessing Renal Involvement and Disease Activity in Systemic Lupus Erythematosus

“…Although antibodies such as anti-double-stranded (ds) DNA and anti-C1q antibodies [ 3 – 8 ] as well as urinalysis and complement consumption [ 9 ] have been shown to correlate with DA [ 2 , 10 , 11 ] and the likelihood of renal involvement in lupus patients [ 1 , 3 ], the additive effect of combined biomarkers is not widely implemented. In addition, recently anti-Ku antibodies, that have mostly been described in the context of idiopathic inflammatory myopathies, have now been reported to be associated with SLE [ 12 ]. However, it is yet unclear whether anti-Ku-positive SLE cases show a higher degree of myositis or other musculoskeletal manifestations.…”