Presence of anti-microbial antibodies in liver cirrhosis--a tell-tale sign of compromised immunity?
BACKGROUND
Bacterial translocation plays important role in the complications of liver cirrhosis. Antibody formation against various microbial antigens is common in Crohn's disease and considered to be caused by sustained exposure to gut microflora constituents. We hypothesized that anti-microbial antibodies are present in patients with liver cirrhosis and may be associated with the development of bacterial infections.


RESULTS
Sera of 676 patients with various chronic liver diseases (autoimmune diseases: 266, viral hepatitis C: 124, and liver cirrhosis of different etiology: 286) and 100 controls were assayed for antibodies to Saccharomyces cerevisiae (ASCA) and to antigens derived from two intestinal bacterial isolates (one gram positive, one gram negative, neither is Escherichia coli). In patients with liver cirrhosis, we also prospectively recorded the development of severe episodes of bacterial infection. ASCA and anti-OMP Plus™ antibodies were present in 38.5% and 62.6% of patients with cirrhosis and in 16% and 20% of controls, respectively (p<0.001). Occurrence of these antibodies was more frequent in cases of advanced cirrhosis (according to Child-Pugh and MELD score; p<0.001) or in the presence of ascites (p<0.001). During the median follow-up of 425 days, 81 patients (28.3%) presented with severe bacterial infections. Anti-microbial antibody titers (p = 0.003), as well as multiple seroreactivity (p = 0.036), was associated with infectious events. In logistic regression analysis, the presence of ascites (OR: 1.62, 95%CI: 1.16-2.25), co-morbidities (OR: 2.22, 95%CI: 1.27-3.86), and ASCA positivity (OR: 1.59, 95%CI: 1.07-2.36) were independent risk factors for severe infections. A shorter time period until the first infection was associated with the presence of ASCA (p = 0.03) and multiple seropositivity (p = 0.037) by Kaplan-Meier analysis, and with Child-Pugh stage (p = 0.018, OR: 1.85) and co-morbidities (p<0.001, OR: 2.02) by Cox-regression analysis.


CONCLUSIONS
The present study suggests that systemic reactivity to microbial components reflects compromised mucosal immunity in patients with liver cirrhosis, further supporting the possible role of bacterial translocation in the formation of anti-microbial antibodies.
Papp
Maria
M
2nd Department of Medicine, University of Debrecen, Debrecen, Hungary. drpappm@yahoo.com
Norman
Gary L
GL
Vitalis
Zsuzsanna
Z
Tornai
Istvan
I
Altorjay
Istvan
I
Foldi
Ildiko
I
Udvardy
Miklos
M
Shums
Zakera
Z
Dinya
Tamas
T
Orosz
Peter
P
Lombay
Bela
B
Par
Gabriella
G
Par
Alajos
A
Veres
Gabor
G
Csak
Timea
T
Osztovits
Janos
J
Szalay
Ferenc
F
Lakatos
Peter Laszlo
PL
D000328:Adult; D000368:Aged; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology*; D000908:Antibodies, Fungal / Q000097:blood / Q000276:immunology*; D001419:Bacteria / Q000276:immunology; D001424:Bacterial Infections / Q000209:etiology / Q000276:immunology*; D018407:Bacterial Physiological Phenomena; D018988:Bacterial Translocation; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D005658:Fungi / Q000276:immunology / Q000502:physiology; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000209:etiology / Q000276:immunology*; D011446:Prospective Studies; D012441:Saccharomyces cerevisiae / Q000276:immunology
D000907:Antibodies, Bacterial; D000908:Antibodies, Fungal