Mannose-binding lectin deficiency confers risk for bacterial infections in a large Hungarian cohort of patients with liver cirrhosis

Altorjay, István; Vitális, Zsuzsanna; Tornai, István; Palatka, Károly; Kacska, Sándor; Farkas, Gyula; Udvardy, M.; Hársfalvi, Jolán; Dinya, Tamás; Orosz, Péter; Lombay, B; Pár, Gabriella; Pár, Alajos; Csák, Tímea; Osztovits, Janos; Szalay, Ferenç; Csepregi, A.; Lakatos, László; Papp, Mária

doi:10.1016/j.jhep.2010.03.028

Cited by 27 publications

(17 citation statements)

References 42 publications

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“…In patients after liver transplantation, our group found that single nucleotide polymorphisms in the MBL, MASP and FNC2 genes were major determinants for the occurrence of clinically significant bacterial infection and mortality. Furthermore, various studies showed that functional deficiencies of MBL, FNC and MASP serum protein levels lead to increased risk of bacterial infection in patients with cirrhosis . In our study we did not confirm that the genetic profile of the lectin pathway of complement activation had a major impact on the occurrence of bacterial infection in patients with decompensated cirrhosis.…”

Section: Discussioncontrasting

confidence: 92%

“…Polymorphisms in the MBL2 gene, for instance, are known to affect proper lectin composition and impair its activity . In patients with cirrhosis, deficiency in MBL protein serum levels is reported to be associated with an increased risk of and shorter time to developing bacterial infection . Low levels of serum ficolin were found to be associated with a higher risk of occurrence of cirrhosis‐associated bacterial infections …”

Section: Introductionmentioning

confidence: 99%

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Genetic variants of innate immunity receptors are associated with mortality in cirrhotic patients with bacterial infection

Schaapman

Amorós

Reijden

et al. 2020

Liver International

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Background & Aims Acute‐on‐chronic liver failure (ACLF) is characterized by acute decompensation of cirrhosis (AD), organ failure(s) and high risk of short‐term mortality with bacterial infection frequently as precipitating event. Innate immune pattern recognition receptors and members of the lectin pathway of complement activation are crucial to the innate immune response to pathogens. The aim of this study was to investigate whether single nucleotide polymorphisms (SNPs) of innate immune components are associated with the occurrence of bacterial infections or mortality in patients with cirrhosis hospitalized for AD or ACLF. Methods Twenty‐one innate immunity SNPs with known functional implications were genotyped in 826 AD/ACLF patients included in the CANONIC study. Associations between baseline characteristics of the patients, the occurrence of bacterial infections and survival rate at 90 days of follow‐up in relation to the innate immunity genetic variants were analysed. Results The NOD2‐G908R genetic variant was associated with mortality (HR 2.25, P = .004) independently of age and MELD Score. This association was also found in a predefined subgroup analysis in patients with bacterial infections (HR 2.78, P < .001) along with MBL_Yx (HR 1.72, P = .008) and MASP2_371 (HR 1.67, P = .012) genetic variants. None of the analysed SNPs were significantly associated with the occurrence of acute bacterial infections or spontaneous bacterial peritonitis in particular. Conclusions Innate immune system‐specific NOD2‐G908R, MBL_Yx and MASP2_371 genetic variants were independently associated with increased risk of short‐term mortality in AD/ACLF patients with bacterial infection.

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Section: Discussioncontrasting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Genetic variants of innate immunity receptors are associated with mortality in cirrhotic patients with bacterial infection

Schaapman

Amorós

Reijden

et al. 2020

Liver International

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“…Recently common variants of nucleotide-binding oligomerization containing domain 2/caspase recruitment domain 15 (NOD2/CARD15) linked to impaired mucosal barrier function were also reported to be risk factors for spontaneous bacterial peritonitis in liver cirrhosis [52]. On the contrary to genetic variation of this and other pathogen-associated molecular patterns' receptors [53], the presence of anti-microbial antibodies were not associated with either the infection-related or the overall mortality in multivariate analysis suggesting that they have no role in the progression (injury, fibrogenesis) and the bacterial complication of the liver cirrhosis. Similarly, no data suggest any pathogenetic role in other diseases associated with high frequency of anti-microbial antibodies for the present.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2010

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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.

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“…Increased susceptibility of Pneumococcus pneumonia in cirrhosis has also been demonstrated due to insufficient deposition of complement C3 on the surface of lungs 79. Altotjay et al 80. has found mannose-binding lectin (MBL) deficiency to be associated with higher infection rate in liver cirrhosis.…”

Section: Complement System and Cirrhosismentioning

confidence: 99%

Immune Dysfunction in Cirrhosis

Noor¹,

Manoria²

2017

Journal of Clinical and Translational Hepatology

119

105

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Cirrhosis due to any etiology disrupts the homeostatic role of liver in the body. Cirrhosis-associated immune dysfunction leads to alterations in both innate and acquired immunity, due to defects in the local immunity of liver as well as in systemic immunity. Cirrhosis-associated immune dysfunction is a dynamic phenomenon, comprised of both increased systemic inflammation and immunodeficiency, and is responsible for 30% mortality. It also plays an important role in acute as well as chronic decompensation. Immune paralysis can accompany it, which is characterized by increase in antiinflammatory cytokines and suppression of proinflammatory cytokines. There is also presence of increased gut permeability, reduced gut motility and altered gut flora, all of which leads to increased bacterial translocation. This increased bacterial translocation and consequent endotoxemia leads to increased blood stream bacterial infections that cause systemic inflammatory response syndrome, sepsis, multiorgan failure and death. The gut microbiota of cirrhotic patients has more pathogenic microbes than that of noncirrhotic individuals, and this disturbs the homeostasis and favors gut translocation. Prompt diagnosis and treatment of such infections are necessary for better survival. We have reviewed the various mechanisms of immune dysfunction and its consequences in cirrhosis. Recognizing the exact pathophysiology of immune dysfunction will help treating clinicians in avoiding its complications in their patients and can lead to newer therapeutic interventions and reducing the morbidity and mortality rates. Citation of this article: Noor MT, Manoria P. Immune dysfunction in cirrhosis.

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Mannose-binding lectin deficiency confers risk for bacterial infections in a large Hungarian cohort of patients with liver cirrhosis

Cited by 27 publications

References 42 publications

Genetic variants of innate immunity receptors are associated with mortality in cirrhotic patients with bacterial infection

Genetic variants of innate immunity receptors are associated with mortality in cirrhotic patients with bacterial infection

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

Immune Dysfunction in Cirrhosis

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