International cohort study of 73 anti-Ku-positive patients: association of p70/p80 anti-Ku antibodies with joint/bone features and differentiation of disease populations by using principal-components analysis.
BACKGROUND
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.


METHODS
Sera 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.


RESULTS
A 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.


CONCLUSIONS
A 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.
Department of Rheumatology, University Medical Centre, Ljubljana, Slovenia.
Katja
K
Lakota
Gerhard G
GG
Thallinger
Snezna
S
Sodin-Semrl
Blaz
B
Rozman
Ales
A
Ambrozic
Matija
M
Tomsic
Sonja
S
Praprotnik
Sasa
S
Cucnik
Katjusa
K
Mrak-Poljsak
Angela
A
Ceribelli
Ilaria
I
Cavazzana
Franco
F
Franceschini
Jiri
J
Vencovsky
Laszlo
L
Czirják
Cecilia
C
Varjú
Gunther
G
Steiner
Martin
M
Aringer
Bojana
B
Stamenkovic
Oliver
O
Distler
Marco
M
Matucci-Cerinic
Tanja
T
Kveder
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D034961:Antigens, Nuclear / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000276:immunology; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D001847:Bone Diseases / Q000097:blood / Q000276:immunology*; D015331:Cohort Studies; D003378:Counterimmunoelectrophoresis; D004268:DNA-Binding Proteins / Q000276:immunology*; D005060:Europe; D005260:Female; D006801:Humans; D007118:Immunoassay; D015151:Immunoblotting; D007592:Joint Diseases / Q000097:blood / Q000276:immunology*; D000072200:Ku Autoantigen; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D017285:Polymyositis / Q000097:blood / Q000276:immunology; D025341:Principal Component Analysis; D012595:Scleroderma, Systemic / Q000097:blood / Q000276:immunology; D012859:Sjogren's Syndrome / Q000097:blood / Q000276:immunology; D055815:Young Adult
D034961:Antigens, Nuclear; D001323:Autoantibodies; D004268:DNA-Binding Proteins; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen