title: Antibodies against PM/Scl-75 and PM/Scl-100 are independent markers for different subsets of systemic sclerosis patients.
abstract: BACKGROUND
  Anti-PM/Scl antibodies are present in sera from patients with polymyositis (PM), systemic sclerosis (SSc), and PM/SSc overlap syndromes. The prevalence of antibodies against the 75- and 100-kDa PM/Scl proteins and their clinical associations have not been studied in SSc patients in detail so far but could provide a valuable tool for risk assessment in these patients. Furthermore, it remains speculative whether commercially available test systems detecting only anti-PM/Scl-100 antibodies are sufficient in SSc patients.
  
  
  METHODS
  Two hundred eighty sera from SSc patients, patients with other connective tissue diseases (n = 209), and healthy blood donors (n = 50) were analyzed for the presence of anti-PM/Scl-75 and anti-PM/Scl-100 antibodies by means of line immunoblot assay. For the SSc patients, possible associations between both subsets of anti-PM/Scl antibodies with clinical and laboratory findings were studied.
  
  
  RESULTS
  The determination of anti-PM/Scl reactivity revealed a diagnostic sensitivity of 12.5% and a specificity of 96.9% for SSc. Among anti-PM/Scl-positive SSc patients, 10.4% and 7.1% were positive for anti-PM/Scl-75 and anti-PM/Scl-100 antibodies, respectively. The highest prevalences of reactivity to PM/Scl were detected in diffuse SSc (19.8%) and overlap syndromes (17.6%). Patients with diffuse SSc showed mainly an anti-PM/Scl-75 response, whereas most cases of overlap syndromes were characterized by reactivity to both PM/Scl antigens. The presence of anti-PM/Scl-75/100 antibodies was associated with muscular and lung involvements as well as with digital ulcers; pulmonary arterial hypertension was found less frequently. Anti-PM/Scl-75 antibodies were detected more frequently in younger and more active patients with joint contractures. Anti-PM/Scl-100 antibodies were associated with creatine kinase elevation; however, gastrointestinal involvements were observed less frequently.
  
  
  CONCLUSIONS
  Anti-PM/Scl antibodies are common in distinct SSc subsets and are associated with several clinical symptoms. They are directed mainly to the PM/Scl-75 antigen. Consequently, the detection of anti-PM/Scl antibodies by tests based only on PM/Scl-100 as an antigen source may miss a relevant number of SSc patients positive for these antibodies.
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité Universitätsmedizin, Humboldt University Berlin, Charitéplatz 1, Berlin 10117, Germany. katharina.hanke@charite.de
authors.forename: Katharina
authors.initials: K
authors.lastname: Hanke
authors.forename: Claudia S
authors.initials: CS
authors.lastname: Brückner
authors.forename: Cornelia
authors.initials: C
authors.lastname: Dähnrich
authors.forename: Dörte
authors.initials: D
authors.lastname: Huscher
authors.forename: Lars
authors.initials: L
authors.lastname: Komorowski
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Meyer
authors.forename: Anthonia
authors.initials: A
authors.lastname: Janssen
authors.forename: Marina
authors.initials: M
authors.lastname: Backhaus
authors.forename: Mike
authors.initials: M
authors.lastname: Becker
authors.forename: Angela
authors.initials: A
authors.lastname: Kill
authors.forename: Karl
authors.initials: K
authors.lastname: Egerer
authors.forename: Gerd R
authors.initials: GR
authors.lastname: Burmester
authors.forename: Falk
authors.initials: F
authors.lastname: Hiepe
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schlumberger
authors.forename: Gabriela
authors.initials: G
authors.lastname: Riemekasten
mesh_terms: D001323:Autoantibodies / Q000097:blood* / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D015415:Biomarkers / Q000097:blood*; D005095:Exoribonucleases; D063326:Exosome Multienzyme Ribonuclease Complex; D006801:Humans; D015151:Immunoblotting; D008875:Middle Aged; D012595:Scleroderma, Systemic / Q000097:blood* / Q000276:immunology* / Q000503:physiopathology; D012680:Sensitivity and Specificity
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D015415:Biomarkers; D005095:Exoribonucleases; D063326:Exosome Multienzyme Ribonuclease Complex; C077044:EXOSC10 protein, human