title: Antimitochondrial antibodies of immunoglobulin G3 subclass are associated with a more severe disease course in primary biliary cirrhosis.
abstract: OBJECTIVE
  Primary biliary cirrhosis (PBC) is characterised by the presence of immunoglobulin (Ig) G antimitochondrial antibodies (AMA), which are routinely detected by indirect immunofluorescence (IFL) using composite rodent tissue substrate. The IgG subclass distribution and clinical significance of IFL-detected AMA in patients with PBC have not been previously studied in detail.
  
  
  METHODS
  We have examined IgG subclass-specific AMA detected by IFL on rodent liver, kidney and stomach tissue substrate using affinity-purified IgG subclass monospecific antisera as revealing reagents in 95 AMA-positive PBC patients from Greece.
  
  
  RESULTS
  AMA of any of the IgG1, IgG2 or IgG3 subclasses were present in 89/95 (93.7%) patients. Among those 89, 55 (61.8%) had IgG1, 2, 3 AMA positivity; eight (9%) had IgG1, 2; seven (7.9%) had IgG2, 3; eight (9%) had IgG1, 3; nine (10.1%) had IgG1 subclass and two (2.2%) single IgG3 AMA reactivity. IgG4 AMA was absent. IgG3 titres were higher than IgG2 and IgG1 (P<0.001) and IgG1 higher than IgG2 (P<0.001). IgG3 AMA-positive patients had a histologically more advanced disease (P<0.01) and were more frequently cirrhotic compared with those who were negative (P<0.01). There was a positive correlation between AMA IgG3 titre and Mayo risk score (r=0.55, P=0.009, Spearman's correlation).
  
  
  CONCLUSIONS
  Our findings suggest that AMA are not restricted to a specific IgG subclass. AMA of the IgG3 subclass are associated with a more severe disease course, possibly reflecting the peculiar ability of this isotype to engage mediators of damage.
authors.affiliation: Academic Liver Unit and Research Laboratory of Internal Medicine, Department of Medicine, University of Thessaly, Larissa, Greece.
authors.forename: Eirini I
authors.initials: EI
authors.lastname: Rigopoulou
authors.forename: Edward T
authors.initials: ET
authors.lastname: Davies
authors.forename: Dimitrios-Petrou
authors.initials: DP
authors.lastname: Bogdanos
authors.forename: Christos
authors.initials: C
authors.lastname: Liaskos
authors.forename: Maria
authors.initials: M
authors.lastname: Mytilinaiou
authors.forename: George K
authors.initials: GK
authors.lastname: Koukoulis
authors.forename: George N
authors.initials: GN
authors.lastname: Dalekos
authors.forename: Diego
authors.initials: D
authors.lastname: Vergani
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000097:blood*; D018450:Disease Progression; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007132:Immunoglobulin Isotypes / Q000097:blood*; D008105:Liver Cirrhosis, Biliary / Q000097:blood / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D008930:Mitochondria, Liver / Q000276:immunology*; D011237:Predictive Value of Tests
chemical_list: D001323:Autoantibodies; D007132:Immunoglobulin Isotypes