Brief Article
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World J Gastroenterol. Oct 21, 2010; 16(39): 4938-4943
Published online Oct 21, 2010. doi: 10.3748/wjg.v16.i39.4938
Peri-nuclear antibodies correlate with survival in Greek primary biliary cirrhosis patients
Ourania Sfakianaki, Meri Koulentaki, Maria Tzardi, Elena Tsangaridou, Panayotis A Theodoropoulos, Elias Castanas, Elias A Kouroumalis
Ourania Sfakianaki, Elias A Kouroumalis, Liver Research Laboratory, Medical School, University of Crete, Voutes 71003, Crete, Greece
Meri Koulentaki, Elias A Kouroumalis, Department of Gastroenterology, University Hospital of Heraklion, Voutes 71100, Crete, Greece
Maria Tzardi, Department of Pathology, University Hospital of Heraklion, Voutes 71100, Crete, Greece
Elena Tsangaridou, Panayotis A Theodoropoulos, Department of Biochemistry, Medical School, University of Crete, Voutes 71003, Crete, Greece
Elias Castanas, Department of Experimental Endocrinology, Medical School, University of Crete, Voutes 71003, Crete, Greece
Author contributions: Sfakianaki O and Tsangaridou E performed the research; Koulentaki M collected the data; Tzardi M interpreted the pathological data; Sfakianaki O and Kouroumalis EA interpreted the data; Sfakianaki O and Koulentaki M wrote the manuscript; Koulentaki M, Tzardi M, Theodoropoulos PA, Castanas E and Kouroumalis EA revised the manuscript; Theodoropoulos PA, Castanas E and Kouroumalis EA planned the study; Kouroumalis EA coordinated the study.
Supported by PENED 2003 (03E_66) from the Greek Secretariat of Research and Technology to Theodoropoulos PA
Correspondence to: Ourania Sfakianaki, Biologist, PhD Candidate, Liver Research Laboratory, Medical School, University of Crete, Voutes 71003, Crete, Greece. rsfaki@yahoo.gr
Telephone: +30-2810-394634 Fax: +30-2810-542085
Received: June 15, 2010
Revised: July 18, 2010
Accepted: July 25, 2010
Published online: October 21, 2010
Abstract

AIM: 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.

CONCLUSION: The presence of ANEA and anti-gp210 identifies a subgroup of PBC patients with advanced disease severity and poor prognosis.

Keywords: Primary biliary cirrhosis; Antimitochondrial antibodies; Antinuclear antibodies; Antibodies against nuclear envelope antigens; Anti-gp210 antibodies