Presence of Anti-Microbial Antibodies in Liver Cirrhosis – A Tell-Tale Sign of Compromised Immunity?

Abstract

BackgroundBacterial 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.Methodology/Principal FindingsSera 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/SignificanceThe 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.

Bacterial translocation and changes in the intestinal microbiome associated with alcoholic liver disease

“…Small intestinal bacterial overgrowth has also been found in cirrhotic patients with increasing prevalence corre� sponding with the severity of liver dysfunction -as high as 58%-75% in cirrhotics classified Child-Pugh C [5��62] . Se� ru� antibodies to �icrobial co��onents are also found more frequently in patients with more advanced liver dis� ease [63] . The cultured flora from cirrhotic patients include Bacteroides spp., E. Coli, Corynebacerium spp., Klebsiella spp ., Klebsiella spp , Klebsiella spp., Stomatococcus, Streptoccoci, and Veillonella spp.…”

Intestinal fungi contribute to development of alcoholic liver disease

“…The human intestine can serve as a source of systemic fungal products or fungal infection when the gut barrier is disrupted (11). Patients with cirrhosis frequently either are exposed to fungal products (12) or develop fungal infections, with high mortality (13)(14)(15). Spontaneous fungal peritonitis is mainly caused by Candida species -in particular by Candida albicans in patients with cirrhosis (16).…”

Circulating CD4+ and CD8+ T cells are activated in inflammatory bowel disease and are associated with plasma markers of inflammation

“…Consistent with this, increased levels of lipopolysaccharide (LPS), a component of the Gram-negative bacterial cell wall, are found in the serum of patients with IBD. 9,10 The phenomenon of microbial translocation is not only observed in IBD and has been demonstrated in other diseases including HIV-1 11 and hepatitis B virus 12 infections, hepatic cirrhosis 13 and visceral leishmaniasis, 14 each of which is characterized by abnormalities of either the gut mucosa or hepatic function.…”