Autoantibodies against nuclear pore complexes are associated with more active and severe liver disease in primary biliary cirrhosis.
OBJECTIVE
Antibodies against nuclear pore complexes (NPCs) have been detected in primary biliary cirrhosis (PBC), but their clinical relevance is still unsettled.


METHODS
We tested sera from 171 consecutive PBC patients and 230 control subjects (149 with autoimmune or viral liver diseases, 28 with systemic lupus erythematosus, and 53 healthy) by immunoblotting for antibodies against purified human NPCs.


RESULTS
Antibodies to NPCs were detected in 27% of the patients with PBC, were highly specific (97%), and were not associated with antimitochondrial antibodies. Their prevalence was higher in symptomatic patients (36 vs. 16%, P < 0.01) and was associated (P < 0.001) with more severe disease, as assessed by the presence of cirrhosis or its complications (13% prevalence in patients without cirrhosis, 31% in uncomplicated, and 54% in complicated cirrhosis), or by the application of the Mayo prognostic model (12% in the lowest, 21% in the median, 47% in the highest score tertile). Positive patients had higher levels of serum bilirubin (2.2 +/- 3.7 vs. 1.0 +/- 1.1 mg/dl, P < 0.01) and more marked inflammatory infiltrates on liver biopsy (P < 0.05).


CONCLUSIONS
Autoantibodies to NPCs are more prevalent in PBC patients than in controls and are strongly associated with more active and severe disease.
Invernizzi
P
P
Department of Medicine, Surgery and Dentistry, San Paolo School of Medicine, University of Milan, Italy. pietro.invernizzi@unimi.it
Podda
M
M
Battezzati
P M
PM
Crosignani
A
A
Zuin
M
M
Hitchman
E
E
Maggioni
M
M
Meroni
P L
PL
Penner
E
E
Wesierska-Gadek
J
J
D001323:Autoantibodies / Q000032:analysis*; D001663:Bilirubin / Q000097:blood; D006801:Humans; D008099:Liver / Q000473:pathology; D008105:Liver Cirrhosis, Biliary / Q000097:blood / Q000150:complications / Q000276:immunology* / Q000473:pathology*; D008107:Liver Diseases / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008875:Middle Aged; D008962:Models, Theoretical; D022022:Nuclear Pore / Q000276:immunology*; D011379:Prognosis; D012016:Reference Values; D012720:Severity of Illness Index
D001323:Autoantibodies; D001663:Bilirubin