We retrospectively analysed the prevalence and clinical features associated to anti-Ku antibodies in patients affected by different autoimmune diseases. Anti-Ku antibodies are detected in 147 sera out of 7239 anti-ENA positive sera (2%). They are found in 2% of patients with systemic sclerosis (SSc) (8 out of 379), 1.8% of systemic lupus erythematosus (SLE) (7 out of 372) and 1.8% of undifferentiated connective tissue disease (UCTD) (9 out of 496) and more rarely in Sjögren Syndrome and rheumatoid arthritis. Most of anti-Ku positive patients were affected by UCTD and overlap syndromes, including polymyositis, SSc and SLE. Interstitial lung disease, myositis, articular symptoms, Raynaud’s phenomenon and sicca represents the main clinical features detected in our cohort. The rate and severity of pulmonary disease is similar to those found in other SSc patients. Isolated anti-Ku were detected in about 47% of sera. No clinical differences were observed between these patients and subjects with multiple anti-nuclear specificities. However, anti-Ku are usually detected in association with other serological markers in SLE and Sjögren Syndrome, while they occurred isolated in SSc and polymyositis.
1 Walker JR Corpina RA Goldberg J . Structure of the Ku heterodimer bound to DNA and its implications for double-strand break repair.Nature2001; 412: 607 – 614 .
2.
2 Ju YJ Lee KH Park JE . Decreased expression of DNA repair proteins Ku70 and Mre11 is associated with aging and may contribute to the cellular senescence.Exp Mol Med2006; 38: 686 – 693 .
3.
3 Ribers–Zamora A Mihalek I Lichtarge O Bertuch AA . Distinct faces of the Ku heterodimer mediate DNA repair and telomeric functions.Nat Struct Mol Biol2007; 14: 301 – 307 .
4.
4 Silvera D Koloteva–Levine N Burma S Elroy–Stein O . Effect of Ku proteins on IRES-mediated translation.Biol Cell2006; 98: 353 – 361 .
5.
5 Mimori T Azikuki M Yamagata H Inada S Yoshida S Homma M . Characterization of a high molecular weight acidic nuclear protein recognised by autoantibodies from patients with polymyositis-scleroderma overlap.J Clin Invest1981; 68: 611 – 620 .
6.
6 Reeves WH . Use of monoclonal antibodies for the characterization of novel DNA-binding proteins recognised by human autoimmune sera.J Exp Med1985; 616: 419 – 425 .
7.
7 Franceschini F Cavazzana I Generali D . Anti-ku antibodies in connective tissue diseases: clinical and serological evaluation of 14 patients.J Rheumatol2002; 29: 1393 – 1397 .
8.
8 Cooley HM Melny BJ Gleeson R Greco T Kay TWH . Clinical and serological associations of anti-Ku antibody.J Rheumatol1999; 26: 563 – 567 .
9.
9 Wang J Satoh M Kabir F . Increased prevalence of autoantibodies to ku antigens in african american versus white patients with systemic lupus erythematosus.Arthritis Rheum2001; 44: 2367 – 2370 .
10.
10 Yamamoto AM Amoura Z Johannet C . Quantitative radioligand assays using de novo-synthesized recombinant autoantigens in connective tissue diseases: new tools to approach the pathogenic significance of anti-RNP antibodies in rheumatic diseases.Arthritis Rheum2000; 43: 689 – 698 .
11.
11 Yaneva M Arnett FC . Antibodies against Ku protein in sera from patients with autoimmune diseases.Clin Exp Rheumatol1989; 76: 366 – 372 .
12.
12 Mimori T . Clinical significance of anti-Ku autoantibodies – A serological marker of overlap syndrome?Int Med2002; 41: 1096 – 1098 .
13.
13 Isern AR Yaneva M Parke A Rothfield N Dantzker D Rich S . Autoantibodies in patients with primary pulmonary hypertension: association with anti-Ku.Am J Med1992; 93: 307 – 312 .
14.
14 Tan EM Cohen AM Fries JF . The 1982 revised criteria for the classification of systemic lupus erythematosus.Arthritis Rheum1982; 25: 1271 – 1277 .
15.
15 Arnett FC Edworthy SM Bloch DA . The american rheumatism association 1987 revised criteria for the classification of rheumatoid arthritis.Arthritis Rheum1988; 31: 315 – 324 .
16.
16 Masi AT Rodnan GP Medsger TA . Preliminary criteria for the classification of systemic sclerosis (scleroderma).Arthritis Rheum1980; 23: 581 – 590 .
17.
17 LeRoy EC Black C Fleischmajer R . Scleroderma (systemic sclerosis): classification subsets and pathogenesis.J Rheumatol1988; 15: 202 – 205 .
18.
18 Bohan A Peter JB . Polymyositis and dermatomyositis.N Engl J Med1965; 292: 344 – 347 .
19.
19 Vitali C Bombardieri S Jonsson R . European Study Group on Classification Criteria for Sjogren’s syndrome: Classification criteria for Sjogren’s syndrome: a revised version of the European criteria proposed by the American-European Consensus group.Ann Rheum Dis2002; 61: 554 – 558 .
20.
20 Mosca M Neri R Bombardieri S . Undifferentiated connective tissue disease (UCTD): a review of the literature and a proposal for preliminary classification criteria.Clin Exp Rheumatol1999; 17: 615 – 620 .
21.
21 Medsger TA Silman AJ Steen VD . A disease severity scale for systemic sclerosis: development and testing.J Rheumatol1999; 26: 2159 – 2167 .
22.
22 Bernstein RM Bunn CC Hughes GRV . Identification of antibodies to acidic antigens by counterimmunoelectrophoresis.Ann Rheum Dis1982; 41: 554 – 555 .
23.
23 Clark G Reichlin M Tomasi TB . Characterization of a soluble cytoplasmic antigen reactive with sera from patients with systemic lupus erythematosus.J Immunol1969; 102: 117 – 122 .
24.
24 Venables PJW Smith PR Maini RN . Purification and characterization of the Sjögren’s Syndrome A and B antigens.Clin Exp Immunol1983; 54: 731 – 738 .
25.
25 Harris EN . The second International anti-cardiolipin standardization workshop. The Kingston anti-phospholipid antibody study (KAPS) group.Ann J Clin Pathol1990; 94: 476 – 484 .
26.
26 Balestrieri G Tincani A Spatola L . Antibeta2glicoprotein 1: a marker of antiphospholipid syndrome?Lupus1995; 4: 122 – 130 .
27.
27 Koenig M Fritzler MJ Targoff IN Troyanov Y Senecal JL . Heterogeneity of autoantibodies in 100 patients with autoimmune myositis: insights into clinical features and outcomes.Arthritis Res Ther2007; 9: R78 .
28.
28 Sherer Y Gorstein A Fritzler MJ Shoenfeld Y . Autoantibody explosion in systemic lupus erythematosus: more than 100 different antibodies found in SLE patients.Sem Arth Rheum2004; 34: 501 – 537 .
29.
29 Zhuang H Narain S Loy AC Satoh M Reeves WH . Ku and Ki autoantibodies. In: Y ShoenfeldME GershwinPL Meroni , (eds), Autoantibodies.Oxford, UK : Elsevier ; 2007. pp. 177–184.
30.
30 Yamanishi Y Maeda H Katayama S Ishioka S Yamakido M . Scleroderma-polymyositis overlap syndrome associated with anti-Ku antibody and rimmed vacuole formation.J Rheumatol1996; 23: 1991 – 1994 .
31.
31 Nitta Y Muramatsu M . A juvenile case of overlap syndrome of systemic lupus erythematosus and polymyositis, later accompanied by systemic sclerosis with the development of anti-Scl-70 and anti-Ku antibodies.Pediatr Dermatol2000; 17: 381 – 383 .
32.
32 Birdi N Laxer RM Thorner P Fritzler MJ Silvermann ED . Localized scleroderma progressing to systemic disease. Case report and review of the literature.Arthritis Rheum1993; 36: 410 – 415 .
33.
33 Kamei N Yamane K Yamashita Y . Anti-Ku antibody-positive scleroderma-dermatomyositis overlap syndrome developing Graves’ disease and immune thrombocytopenic purpura.Intern Med2002; 41: 1199 – 1203 .
34.
34 Ghirardello A Zampieri S Tarricone E . Clinical implications of autoantibody screening in patients with autoimmune myositis.Autoimmunity2006; 39: 217 – 221 .
