nach oben

Digestive Diseases and Sciences

Erschienen in:

01.10.2013 | Original Article

Clinicopathological Significance of Serum Fractalkine in Primary Biliary Cirrhosis

verfasst von: Kenichi Harada, Yuko Kakuda, Minoru Nakamura, Shinji Shimoda, Yasuni Nakanuma

Erschienen in: Digestive Diseases and Sciences | Ausgabe 10/2013

Einloggen, um Zugang zu erhalten

Abstract

Background

Primary biliary cirrhosis (PBC), characterized by cholangitis and loss of intrahepatic small bile ducts, predominantly affects middle-aged females. We have reported that fractalkine expression associated with chronic inflammation is observed in the damaged bile ducts and periductal vessels of PBC patients, which is closely associated with chronic cholangitis.

Aims

We investigated the association between serum fractalkine levels and clinicopathological findings in PBC patients.

Methods

Liver biopsy specimens before ursodeoxycholic acid treatment and serum samples at the time of liver biopsy and 1 and 2 years after treatment were obtained from 68 PBC patients (M/F = 14/54). Serum fractalkine levels were measured by enzyme-linked immunosorbent assay, and their association with clinicopathological findings (liver function data, autoantibodies, cholangitis activity, hepatitis activity, fibrosis, bile duct loss, and orcein-positive granules) was analyzed.

Results

Serum fractalkine levels were in the range of 0.1–33.2 ng/ml (average, 3.2 ng/ml). They were increased in PBC patients with high degrees of cholangitis activity, a mild degree of hepatitis activity, fibrosis, orcein-positive granules, and early stages. In cases with high serum fractalkine levels, those who exhibited good biochemical responses to treatment mostly showed improved serum fractalkine levels after treatment.

Conclusion

Serum fractalkine levels of PBC patients were high in cases with marked cholangitis activity at early stages. In addition, they closely correlated with the effect of therapy, indicating that fractalkine plays a role in the pathogenesis of initial cholangitis in early stage PBC and consequent chronic cholangitis. Thus, our results suggest that fractalkine is a good candidate for molecular-targeted treatment.

Bourd-Boittin K, Basset L, Bonnier D, L’Helgoualc’h A, Samson M, Theret N. CX3CL1/fractalkine shedding by human hepatic stellate cells: contribution to chronic inflammation in the liver. J Cell Mol Med. 2009;13:1526–1535.PubMedCrossRef

Jones BA, Beamer M, Ahmed S. Fractalkine/CX3CL1: a potential new target for inflammatory diseases. Mol Interv. 2010;10:263–270.PubMedCrossRef

Nishimura M, Kuboi Y, Muramoto K, Kawano T, Imai T. Chemokines as novel therapeutic targets for inflammatory bowel disease. Ann N Y Acad Sci. 2009;1173:350–356.PubMedCrossRef

Nakanuma Y, Ohta G. Histometric and serial section observations of the intrahepatic bile ducts in primary biliary cirrhosis. Gastroenterology. 1979;76:1326–1332.PubMed

Shimoda S, Ishikawa F, Kamihira T, et al. Autoreactive T-cell responses in primary biliary cirrhosis are proinflammatory whereas those of controls are regulatory. Gastroenterology. 2006;131:606–618.PubMedCrossRef

Shimoda S, Miyakawa H, Nakamura M, et al. CD4 T-cell autoreactivity to the mitochondrial autoantigen PDC-E2 in AMA-negative primary biliary cirrhosis. J Autoimmun. 2008;31:110–115.PubMedCrossRef

Shimoda S, Nakamura M, Ishibashi H, Hayashida K, Niho Y. HLA DRB4 0101-restricted immunodominant T cell autoepitope of pyruvate dehydrogenase complex in primary biliary cirrhosis: evidence of molecular mimicry in human autoimmune diseases. J Exp Med. 1995;181:1835–1845.PubMedCrossRef

Shimoda S, Nakamura M, Ishibashi H, et al. Molecular mimicry of mitochondrial and nuclear autoantigens in primary biliary cirrhosis. Gastroenterology. 2003;124:1915–1925.PubMedCrossRef

Isse K, Harada K, Zen Y, et al. Fractalkine and CX3CR1 are involved in the recruitment of intraepithelial lymphocytes of intrahepatic bile ducts. Hepatology. 2005;41:506–516.PubMedCrossRef

10.

Shimoda S, Harada K, Niiro H, et al. Interaction between Toll-like receptors and natural killer cells in the destruction of bile ducts in primary biliary cirrhosis. Hepatology. 2011;53:1270–1281.PubMedCrossRef

11.

Harada K, Ohira S, Isse K, et al. Lipopolysaccharide activates nuclear factor-kappaB through toll-like receptors and related molecules in cultured biliary epithelial cells. Lab Invest. 2003;83:1657–1667.PubMedCrossRef

12.

Nakanuma Y, Zen Y, Harada K, et al. Application of a new histological staging and grading system for primary biliary cirrhosis to liver biopsy specimens: Interobserver agreement. Pathol Int. 2010;60:167–174.PubMedCrossRef

13.

Rigopoulou EI, Davies ET, Pares A, et al. Prevalence and clinical significance of isotype specific antinuclear antibodies in primary biliary cirrhosis. Gut. 2005;54:528–532.PubMedCrossRef

14.

Invernizzi P, Selmi C, Ranftler C, Podda M, Wesierska-Gadek J. Antinuclear antibodies in primary biliary cirrhosis. Semin Liver Dis. 2005;25:298–310.PubMedCrossRef

15.

Nakamura M, Kondo H, Mori T, et al. Anti-gp210 and anti-centromere antibodies are different risk factors for the progression of primary biliary cirrhosis. Hepatology. 2007;45:118–127.PubMedCrossRef

16.

Nakamura M, Komori A, Ito M, et al. Predictive role of anti-gp210 and anticentromere antibodies in long-term outcome of primary biliary cirrhosis. Hepatol Res. 2007;37:S412–S419.PubMedCrossRef

17.

Nakamura M, Shimizu-Yoshida Y, Takii Y, et al. Antibody titer to gp210-C terminal peptide as a clinical parameter for monitoring primary biliary cirrhosis. J Hepatol. 2005;42:386–392.PubMedCrossRef

18.

Itoh S, Ichida T, Yoshida T, et al. Autoantibodies against a 210 kDa glycoprotein of the nuclear pore complex as a prognostic marker in patients with primary biliary cirrhosis. J Gastroenterol Hepatol. 1998;13:257–265.PubMedCrossRef

19.

Kumar D, Tandon RK. Use of ursodeoxycholic acid in liver diseases. J Gastroenterol Hepatol. 2001;16:3–14.PubMedCrossRef

Titel: Clinicopathological Significance of Serum Fractalkine in Primary Biliary Cirrhosis
verfasst von: Kenichi Harada
Yuko Kakuda
Minoru Nakamura
Shinji Shimoda
Yasuni Nakanuma
Publikationsdatum: 01.10.2013
Verlag: Springer US
Erschienen in: Digestive Diseases and Sciences / Ausgabe 10/2013
Print ISSN: 0163-2116
Elektronische ISSN: 1573-2568
DOI: https://doi.org/10.1007/s10620-013-2734-6

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

Reizdarmsyndrom: Diäten wirksamer als Medikamente

29.04.2024 Reizdarmsyndrom Nachrichten

Bei Reizdarmsyndrom scheinen Diäten, wie etwa die FODMAP-arme oder die kohlenhydratreduzierte Ernährung, effektiver als eine medikamentöse Therapie zu sein. Das hat eine Studie aus Schweden ergeben, die die drei Therapieoptionen im direkten Vergleich analysierte.

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

25.04.2024 Allergien und Intoleranzreaktionen Nachrichten

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Background

Aims

Methods

Results

Conclusion

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 10/2013

Is Pyloric Gland Metaplasia in Ileal Pouch Biopsies a Marker for Crohn’s Disease?

Predictors of All-Cause Mortality and Liver-Related Mortality in Patients with Non-Alcoholic Fatty Liver Disease (NAFLD)

United States Women Receive More Curative Treatment for Hepatocellular Carcinoma Than Men

The Value of Early Wireless Esophageal pH Monitoring in Diagnosing Functional Heartburn in Refractory Gastroesophageal Reflux Disease

The Role of Food for the Formation and Prevention of Gastrointestinal Lesions Induced by Aspirin in Cats

Downregulation of Beclin1 and Impairment of Autophagy in a Small Population of Colorectal Cancer