Abstract
IntroductionAn international cohort study of 73 anti-Ku-positive patients with different connective tissue diseases was conducted to differentiate the anti-Ku-positive populations of patients based on their autoantibody profile and clinical signs/symptoms and to establish possible correlations between antibodies against Ku p70 and Ku p80 with autoimmune diseases.MethodsSera of anti-Ku-positive patients were collected from six European centers and were all secondarily tested (in the reference center); 73 were confirmed as positive. Anti-Ku antibodies were detected with counter-immunoelectrophoresis (CIE), line immunoassay (LIA), and immunoblot analyses. All clinical and laboratory data were follow-up cumulative data, except for anti-Ku antibodies. Statistical analyses were performed by using R (V 2.12.1). The Fisher Exact test was used to evaluate the association between anti-Ku antibodies and diagnosis, gender, clinical signs, and other observed antibodies. The P values were adjusted for multiple testing. Separation of disease populations based on the presence of antibodies and clinical signs was investigated by principal-components analysis, which was performed by using thr// R's prcomp function with standard parameters.ResultsA 16% higher prevalence of anti-Ku p70 was found over anti-Ku p80 antibodies. In 41 (57%) patients, a combination of both was detected. Five (7%) patients, who were CIE and/or LIA anti-Ku positive, were negative for both subsets, as detected with the immunoblot; 31% of the patients had undifferentiated connective tissue disease (UCTD); 29% had systemic sclerosis (SSc); 18% had systemic lupus erythematosus (SLE); 11% had rheumatoid arthritis; 7% had polymyositis; and 3% had Sjögren syndrome.ConclusionsA significant positive association was found between female patients with anti-Ku p70 and joint/bone features, and a significant negative association was found between female patients with anti-Ku p80 only and joint/bone features (P = 0.05, respectively). By using the first and the third components of the principal-component analysis (PCA) with 29 parameters evaluated, we observed that the anti-Ku-positive population of UCTD patients had overlapping parameters, especially with SLE, as opposed to SSc, which could be helpful in delineating UCTD patients.
Highlights
An international cohort study of 73 anti-Ku-positive patients with different connective tissue diseases was conducted to differentiate the anti-Ku-positive populations of patients based on their autoantibody profile and clinical signs/symptoms and to establish possible correlations between antibodies against Ku p70 and Ku p80 with autoimmune diseases
Hep-2 patterns were detected with indirect immunofluorescence, rheumatoid factor, with latex fixation test and Waaler Rose reaction, anti-cyclic citrullinated protein antibodies with enzyme-linked immunosorbent assay (ELISA; Immunoscan CCPlus, Euro-Diagnostica AB, Malmö, Sweden), antiphospholipid antibodies (aPLs) with an in-house ELISA and anti-dsDNA antibodies with an inhouse FARR-RIA assay
We showed a higher prevalence of antibodies against Ku p70 as compared with anti-Ku p80
Summary
An international cohort study of 73 anti-Ku-positive patients with different connective tissue diseases was conducted to differentiate the anti-Ku-positive populations of patients based on their autoantibody profile and clinical signs/symptoms and to establish possible correlations between antibodies against Ku p70 and Ku p80 with autoimmune diseases. The Ku complex is a heterodimer made of p70 and p80 subunits that play major roles in DNA repair, transcriptional regulation, and replication and have been involved in telomere maintenance, V(D)J recombination, and development of the brain. Ku p70 and Ku p80 genes are localized on different chromosomes (22q13 and 2q33, respectively). Their proteins share sequence homologies, as well as display marked structural homologies. Ku p70 and Ku p80 are generally believed to form and function as a heterodimer, but each has its own unique activities. Whereas p70 resembles a transcriptional activator, and its DNA-binding domain has been localized to its C-terminus, p80 does not seem to bind DNA and may be involved in interactions with other proteins [4]. Ku70-knockout mice showed deficiencies in subgroups of mature T lymphocytes and a significant incidence of thymic lymphoma, whereas Ku p80-knockout mice had arrested T-and B-cell development at early stages and caused growth retardation [5,6]
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