Antimitochondrial antibodies of immunoglobulin G3 subclass are associated with a more severe disease course in primary biliary cirrhosis.
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.
Rigopoulou
Eirini I
EI
Academic Liver Unit and Research Laboratory of Internal Medicine, Department of Medicine, University of Thessaly, Larissa, Greece.
Davies
Edward T
ET
Bogdanos
Dimitrios-Petrou
DP
Liaskos
Christos
C
Mytilinaiou
Maria
M
Koukoulis
George K
GK
Dalekos
George N
GN
Vergani
Diego
D
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
D001323:Autoantibodies; D007132:Immunoglobulin Isotypes