title: Validity of internal expression of the major histocompatibility complex class I in the diagnosis of inflammatory myopathies.
abstract: OBJECTIVE
  The inflammatory myopathies (IMs) are a group of disorders characterised by weakness and inflammation of the skeletal muscles. Muscle biopsy is the most crucial test to confirm the clinical diagnosis, but also the most common cause of misdiagnosis. There are currently no markers specific or sensitive enough to distinguish IMs from other diseases with similar clinical and morphological features, and an international multidisciplinary effort is under way to develop new classification criteria for IMs.
  
  
  METHODS
  Standards for Reporting of Diagnostic Accuracy recommendations to validate a diagnostic test based on the quantification of internal major histocompatibility complex class I (MHC-I) positive fibres were adopted. MHC-I immunostained specimens from 64 patients were scored by two independent blinded investigators, and the percentage of positive fibres was determined. Agreement between investigators was evaluated with the k-weighted statistic. The receiver operating characteristic curve, area under the curve, sensitivity, specificity, and positive and negative predictive values of each percentage range of positive fibres versus the diagnosis of IM were calculated.
  
  
  RESULTS
  The main difference between IM and non-inflammatory samples was the number of internal MHC-I positive fibres. The k-weighted value was 0.89 for a percentage of MHC-I positive fibres above 50%; the positive predictive value was 100%, and the negative predictive value was 94%.
  
  
  CONCLUSIONS
  This is the first study on the validity of a quantitative analysis of internal MHC-I positive fibres for an IM diagnosis performed according to Standards for Reporting of Diagnostic Accuracy recommendations. The interobserver agreement was almost perfect, thus making the method reproducible. Applying an MHC-I cut-off above 50% is an optimal marker for polymyositis (PM) and dermatomyositis (DM) diagnosis.
authors.affiliation: Dipartimento Clinico di Scienze Radiologiche e Istocitopatologiche, Alma Mater Studiorum, Università di Bologna, Bologna, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Salaroli
authors.forename: Elisa
authors.initials: E
authors.lastname: Baldin
authors.forename: Valentina
authors.initials: V
authors.lastname: Papa
authors.forename: Rita
authors.initials: R
authors.lastname: Rinaldi
authors.forename: Lucia
authors.initials: L
authors.lastname: Tarantino
authors.forename: Lucilla Badiali
authors.initials: LB
authors.lastname: De Giorgi
authors.forename: Marco
authors.initials: M
authors.lastname: Fusconi
authors.forename: Nazzarena
authors.initials: N
authors.lastname: Malavolta
authors.forename: Riccardo
authors.initials: R
authors.lastname: Meliconi
authors.forename: Roberto
authors.initials: R
authors.lastname: D'Alessandro
authors.forename: Giovanna
authors.initials: G
authors.lastname: Cenacchi
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry / Q000592:standards; D007558:Italy; D008297:Male; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal / Q000276:immunology*; D009220:Myositis / Q000175:diagnosis* / Q000276:immunology; D015588:Observer Variation; D011237:Predictive Value of Tests; D012372:ROC Curve; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; D015395:Histocompatibility Antigens Class I