title: Most patients with cancer-associated dermatomyositis have antibodies to nuclear matrix protein NXP-2 or transcription intermediary factor 1γ.
abstract: OBJECTIVE
  Since dermatomyositis (DM) is associated with an increased risk of malignancy, accurate identification of patients likely to harbor cancers is important. Using immunoprecipitations from radiolabeled cell lysates, several groups recently showed that anti-transcription intermediary factor 1γ (anti-TIF-1γ) antibodies are associated with malignancy in DM. We undertook this study to develop sensitive, specific assays to detect antibodies against TIF-1γ and nuclear matrix protein NXP-2 and to evaluate their association with malignancy in DM.
  
  
  METHODS
  To detect anti-TIF-1γ antibodies, immunoprecipitations were performed using lysates made from HeLa cells overexpressing TIF-1γ, with detection by immunoblotting. Anti-NXP-2 antibodies were assayed by immunoprecipitation using (35) S-methionine-labeled NXP-2 generated by in vitro transcription/translation. We analyzed patient sera from DM cohorts seen at the Stanford University Dermatology Clinic (n = 111) and the Johns Hopkins Myositis Center (n = 102).
  
  
  RESULTS
  A total of 17% and 38% of patients had antibodies against NXP-2 and TIF-1γ, respectively. Reactivity against either NXP-2 or TIF-1γ identified 83% of patients with cancer-associated DM. In addition to older age and male sex, cancer was associated with antibodies to NXP-2 or TIF-1γ on multivariate analysis (odds ratio 3.78 [95% confidence interval 1.33-10.8]). Stratification by sex revealed that anti-NXP-2 was specifically associated with cancer in males (odds ratio 5.78 [95% confidence interval 1.35-24.7]).
  
  
  CONCLUSIONS
  These studies demonstrate that anti-NXP-2 and anti-TIF-1γ antibodies are frequent DM specificities (found in 55% of patients) and are present in most patients with cancer-associated DM.
authors.affiliation: Stanford University School of Medicine, Stanford, California.
authors.forename: David F
authors.initials: DF
authors.lastname: Fiorentino
authors.forename: Lorinda S
authors.initials: LS
authors.lastname: Chung
authors.forename: Lisa
authors.initials: L
authors.lastname: Christopher-Stine
authors.forename: Lisa
authors.initials: L
authors.lastname: Zaba
authors.forename: Shufeng
authors.initials: S
authors.lastname: Li
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Mammen
authors.forename: Antony
authors.initials: A
authors.lastname: Rosen
authors.forename: Livia
authors.initials: L
authors.lastname: Casciola-Rosen
mesh_terms: D000251:Adenosine Triphosphatases / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000032:analysis / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000276:immunology*; D003882:Dermatomyositis / Q000453:epidemiology* / Q000276:immunology*; D005260:Female; D005500:Follow-Up Studies; D006367:HeLa Cells; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology* / Q000276:immunology*; D035463:Pol1 Transcription Initiation Complex Proteins / Q000276:immunology*; D011863:Radioimmunoassay / Q000379:methods; D012307:Risk Factors; D016036:Seroepidemiologic Studies; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D004268:DNA-Binding Proteins; D035463:Pol1 Transcription Initiation Complex Proteins; C428423:RRN3 protein, human; D000251:Adenosine Triphosphatases; C551732:MORC3 protein, human
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