Peri-nuclear antibodies correlate with survival in Greek primary biliary cirrhosis patients.
OBJECTIVE
To investigate possible associations of anti-nuclear envelope antibody (ANEA) with disease severity and survival in Greek primary biliary cirrhosis (PBC) patients.


METHODS
Serum samples were collected at diagnosis from 147 PBC patients (85% female), who were followed-up for a median 89.5 mo (range 1-240). ANEA were detected with indirect immunofluorescence on 1% formaldehyde fixed Hep2 cells, and anti-gp210 antibodies were detected using an enzyme linked immunosorbent assay. Findings were correlated with clinical data, histology, and survival.


RESULTS
ANEA were detected in 69/147 (46.9%) patients and 31/147 (21%) were also anti-gp210 positive. The ANEA positive patients were at a more advanced histological stage (I-II/III-IV 56.5%/43.5% vs 74.4%/25.6%, P = 0.005) compared to the ANEA negative ones. They had a higher antimitochondrial antibodies (AMA) titer (≤ 1:160/> 1:160 50.7%/49.3% vs 71.8%/28.2%, P = 0.001) and a lower survival time (91.7 ± 50.7 mo vs 101.8 ± 55 mo, P = 0.043). Moreover, they had more advanced fibrosis, portal inflammation, interface hepatitis, and proliferation of bile ductules (P = 0.008, P = 0.008, P = 0.019, and P = 0.027, respectively). They also died more frequently of hepatic failure and/or hepatocellular carcinoma (P = 0.016). ANEA positive, anti-gp210 positive patients had a difference in stage (I-II/III-IV 54.8%/45.2% vs 74.4%/25.6%, P = 0.006), AMA titer (≤ 1:160/> 1:160 51.6%/48.4% vs 71.8%/28.2%, P = 0.009), survival (91.1 ± 52.9 mo vs 101.8 ± 55 mo, P = 0.009), and Mayo risk score (5.5 ± 1.9 vs 5.04 ± 1.3, P = 0.04) compared to the ANEA negative patients. ANEA positive, anti-gp210 negative patients had a difference in AMA titer (≤ 1:160/> 1:160 50%/50% vs 71.8%/28.2%, P = 0.002), stage (I-II/III-IV 57.9%/42.1% vs 74.4%/25.6%, P = 0.033), fibrosis (P = 0.009), portal inflammation (P = 0.018), interface hepatitis (P = 0.032), and proliferation of bile ductules (P = 0.031). Anti-gp210 positive patients had a worse Mayo risk score (5.5 ± 1.9 vs 4.9 ± 1.7, P = 0.038) than the anti-gp210 negative ones.


CONCLUSIONS
The presence of ANEA and anti-gp210 identifies a subgroup of PBC patients with advanced disease severity and poor prognosis.
Sfakianaki
Ourania
O
Liver Research Laboratory, Medical School, University of Crete, Voutes 71003, Crete, Greece. rsfaki@yahoo.gr
Koulentaki
Meri
M
Tzardi
Maria
M
Tsangaridou
Elena
E
Theodoropoulos
Panayotis A
PA
Castanas
Elias
E
Kouroumalis
Elias A
EA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000974:Antibodies, Antinuclear / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006115:Greece; D056945:Hep G2 Cells; D006801:Humans; D053208:Kaplan-Meier Estimate; D008099:Liver / Q000276:immunology* / Q000473:pathology; D008105:Liver Cirrhosis, Biliary / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009685:Nuclear Envelope / Q000276:immunology*; D028861:Nuclear Pore Complex Proteins / Q000276:immunology; D009687:Nuclear Proteins / Q000276:immunology*; D011379:Prognosis; D012720:Severity of Illness Index; D013997:Time Factors
D000974:Antibodies, Antinuclear; C063865:NUP210 protein, human; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins