title: Mixed Connective Tissue Disease and Epitope Spreading: An Historical Cohort Study.
abstract: OBJECTIVE
  Mixed connective tissue disease (MCTD) is characterized by the presence of anti-U1-snRNP autoantibodies and a variable set of associated clinical features. Some MCTD patients test positive over time to autoantibodies against Sm, proteins spatially related with U1-snRNP. This situation has been attributed to expanding of the autoimmune response by a phenomenon known as epitope spreading. Our aim was to study the frequency of this phenomenon in MCTD patients and the specific clinical features of those with epitope spreading.
  
  
  METHODS
  All anti-U1-RNP-positive patients (2010-2015) were retrospectively reviewed, and those meeting the MCTD criteria were included in the study. Patients showing epitope spreading were compared with the remainder of the MCTD cohort. In addition, the clinical features of patients with epitope spreading were compared before and after the phenomenon occurred.
  
  
  RESULTS
  Among 72 anti-U1-RNP-positive patients, 40 (37 women) were diagnosed with MCTD. Thirteen MCTD patients (43%) presented epitope spreading, mainly during the first 2 years after the diagnosis of the disease (median, 1.4 years). Patients with epitope spreading had a significantly lower prevalence of skin sclerosis (0% vs. 44%, P = 0.004) and a greater prevalence of interstitial lung disease (46% vs. 15%, P = 0.05) than those without. Arthritis (92% vs. 25%, P = 0.02) and muscle involvement (67% vs. 17%, P = 0.02) were less frequent after epitope spreading had occurred.
  
  
  CONCLUSIONS
  Epitope spreading is common in MCTD, occurring early after the diagnosis. The clinical manifestations in patients with this phenomenon differ from those without, and their clinical features change after the immunological phenomenon has occurred.
authors.affiliation: From the *Internal Medicine and †Immunology Departments, Vall d'Hebron General Hospital, Universitat Autonoma de Barcelona, Barcelona, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Escolà-Vergé
authors.forename: Iago
authors.initials: I
authors.lastname: Pinal-Fernandez
authors.forename: Andreu
authors.initials: A
authors.lastname: Fernandez-Codina
authors.forename: Eduardo L
authors.initials: EL
authors.lastname: Callejas-Moraga
authors.forename: Juan
authors.initials: J
authors.lastname: Espinosa
authors.forename: Ana
authors.initials: A
authors.lastname: Marin
authors.forename: Moises
authors.initials: M
authors.lastname: Labrador-Horrillo
authors.forename: Albert
authors.initials: A
authors.lastname: Selva-O'Callaghan
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000097:blood; D015551:Autoimmunity / Q000276:immunology; D000939:Epitopes / Q000032:analysis / Q000276:immunology; D005260:Female; D065386:Historically Controlled Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D008947:Mixed Connective Tissue Disease / Q000175:diagnosis / Q000453:epidemiology / Q000276:immunology / Q000503:physiopathology; D017412:Ribonucleoprotein, U1 Small Nuclear / Q000276:immunology*; D013030:Spain / Q000453:epidemiology; D063189:Symptom Assessment / Q000379:methods / Q000706:statistics & numerical data
chemical_list: D001323:Autoantibodies; D000939:Epitopes; D017412:Ribonucleoprotein, U1 Small Nuclear