| Abstract |
Primary biliary cirrhosis (PBC) is a chronic inflammatory liver disease of
probable autoimmune etiology. It is characterized by destruction of small
intrahepatic bile ducts and lead to cholestasis, fibrosis, cirrhosis and liver
failure.
Aim
The aim of this study is:
The determination of the frequency of the autoantibodies that
recognize antigens of the nuclear envelope, in the sera of patients with
PBC.
To investigate the importance of the incidence of these autoantibodies
in the diagnosis, prognosis and clinical course of patients with PBC.
Creation of a Data base of patients showing the clinical-laboratory
data, histological features and the results of this study.
Try to identify the cell types targeted by autoantibodies present in
patient sera.
Methods
The detection of antibodies against antigens of the nuclear envelope (ANEA)
was performed an indirect immunofluorescence (IIF) in Hep2 cells cultured in
the laboratory. The detection of gp210 antibodies was performed using the
commercially available ELISA of Quanta lite TM. Also, to identify the cell types
targeted by autoantibodies present in patient sera was performed an indirect
immunofluorescence on paraffin sections.
Various clinical, histological, and serological measurements were compared
using multivariate regression analysis. Fisher’s exact test was used to
compare causes of death between ANEA positive and negative and gp-210
positive and negative patients. The survival time was estimated by the Kaplan-
Meier method, and compared by the Breslow test. A P value < 0.05 was
considered significant.
Results
ANEA were detected in 46.9% of patients. The ANEA positive patients had a
shorter survival period compared with the ANEA negative ones, had higher
AMA titers, they were in advanced histological stage and also they die more
frequently of hepatic failure and/or hepatocellular carcinoma (HCC), while
ANEA negative patients die more frequently as a result of variceal bleeding.
Also, ANEA positive patients had more severe fibrosis, portal inflammation,
interface hepatitis and proliferation of bile ductules than the ANEA negative
ones.
From the 69 ANEA positive patients the 38 (55.1%) were negative for the
anti-gp210 antibodies and the 31 (44.9%) were positive, representing 21% of
all studied patients.
The anti-gp210 positive patients had higher Mayo risk score than the ANEA
positive, anti-gp210 negative patients.
The anti-gp210 positive patients compared with the ANEA negative ones had
significantly higher AMA titer, higher Mayo risk score, shorter survival period
and they were in advanced histological stage.
Comparing the 78 ANEA negative patients with the 38 ANEA positive gp210-
negative patients, we found that ANEA negative ones had statistically
significant lower AMA titers and were at an earlier histological stage. The
ANEA negative patients had less severe fibrosis, portal inflammation,
interface hepatitis, and proliferation of bile ductules.
A total of 21 tissues were tested with homologous serum of patients with
PBC. Of these, 47.6% gave staining in lymphocytes, 38% in cholangiocytes,
33.3% in the hepatocytes, and 85.7% in sinusoidal cells.
PBC serum with a heterologous PBC tissue reduces the above rates at 20%
for lymphocytes, 20% for the cholangiocytes, 13.3% for the hepatocytes and
20% for the sinusoidal cells.
When was used healthy serum in PBC patient tissue there was positive
staining at a percentage of 14.3% in sinusoidal cells. However, when PBC
patient sera were used in the same healthy tissue, then the sera of 3 (14.3%)
patients gave positive staining in cholangiocytes of the tissue.
When, patient sera with disease control (chronic viral hepatitis B and
steatohepatitis) were used with tissues with disease control (steatohepatitis,
acute alcoholic hepatitis, chronic viral hepatitis B and C) gave the following
results: 2 out of 3 sera with chronic viral hepatitis B that were used gave
positive fluorescence in liver sinusoids of patient with steatohepatitis, but
mostly in sinusoidal lymphocytes and not in sinusoidal cells, while 2 out of 3
sera gave positive staining in cholangiocytes and hepatocytes in acute
alcoholic hepatitis patient tissue and one of these sera also gave positive
staining in cholangiocytes of patient with chronic viral hepatitis B.
A total of 8 PBC patient tissues were used in order to detect IgM
autoantibodies using homologous serum. Of these 75% gave positive
staining in lymphocytes, 62.5% in cholangiocytes, 37.5% in hepatocytes and
50% in sinusoidal cells.
Conclusions
In conclusion, our data confirm that, in Greek PBC patients, there is a
correlation between the presence of ANEA antibodies and disease severity
and shorter survival. The presence of anti-gp210 seems to be an additional
factor, reducing survival.
The study of the tissues showed that antibodies against sinusoidal cells
appear to be characteristic of primary biliary cirrhosis, as shown by this rough
study.
|
Ρόλος αυτοαντισωμάτων που αναγνωρίζουν χαρακτηρισμένα και νέα αυτοαντιγόνα του πυρηνικού φακέλου στη διάγνωση, πρόγνωση και θεραπευτική ανταπόκριση ασθενών με πρωτοπθή χολική κίρρωση
