Role of Antinuclear Antibodies in Primary Biliary Cholangitis

AbstractThe autoantibody profile of primary biliary cholangitis (PBC) includes antinuclear antibodies (ANA) which are detectable by indirect immunofluorescence in more than 50% of PBC patients. One of the two immunofluorescence patterns which are historically considered “PBC-specific” is the so-called “multiple nuclear dots” (MND) targeting nuclear body proteins such as Sp100, Sp140, Sp140L proteins, promyelocytic leukemia protein (PML) and small ubiquitin-related modifier proteins (SUMO). It has been hypothesized a role of nuclear body protein alterations in immune disorders such as PBC, thus suggesting novel and more refined therapeutic approaches.

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Clustering Reveals the Prognostic Role of Serum Albumin Values Within the Normal Range in Patients with Primary Biliary Cholangitis

Digestive and Liver Disease ◽

10.1016/j.dld.2020.12.023 ◽

2021 ◽

Vol 53 ◽

pp. S5

Author(s):

A. Gerussi ◽

D. Verda ◽

D.P. Bernasconi ◽

M. Carbone ◽

A. Komori ◽

...

Keyword(s):

Serum Albumin ◽

Primary Biliary Cholangitis ◽

Prognostic Role ◽

Normal Range

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AB0036 Role of programmed death-1 pathway on cd8+ t cells cytotoxicity in primary biliary cholangitis

10.1136/annrheumdis-2018-eular.1859 ◽

2018 ◽

Author(s):

S. Zhang ◽

X. Tao ◽

L. Wang ◽

L. Zhao ◽

J. Sun ◽

...

Keyword(s):

T Cells ◽

Cd8 T Cells ◽

Primary Biliary Cholangitis ◽

Programmed Death ◽

Programmed Death 1

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Dysregulation of Circulating FGF19 and Bile Acids in Primary Biliary Cholangitis-Autoimmune Hepatitis Overlap Syndrome

BioMed Research International ◽

10.1155/2020/1934541 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Zhanyi Li ◽

Yu Liu ◽

Fangji Yang ◽

Jiahui Pang ◽

Yuankai Wu ◽

...

Keyword(s):

Autoimmune Hepatitis ◽

Bile Acids ◽

Overlap Syndrome ◽

Primary Biliary Cholangitis ◽

Strongly Correlated ◽

Adequate Treatment ◽

End Stage ◽

Fibroblast Growth Factor 19 ◽

Total Bile Acids

Background. Primary biliary cholangitis-autoimmune hepatitis overlap syndrome (PBC-AIH OS), which exhibits features between autoimmune hepatitis and cholestasis, is a common condition and usually shows a progressive course toward cirrhosis and liver failure without adequate treatment. Synthesis of bile acids (BAs) plays an important role in liver injury in cholestasis, and the process is regulated by fibroblast growth factor 19 (FGF19). The overall role of circulating FGF19 in BA synthesis and PBC-AIH OS requires further investigation. Methods. We analyzed BA synthesis and correlated clinical parameters with serum BAs and FGF19 in 35 patients with PBC-AIH OS. Serum concentrations of 7alpha-hydroxycholest-4-en-3-one (C4) were used to quantify the synthesis of BA directly. Results. Serum FGF19 levels were higher, while C4 levels were substantially lower in PBC-AIH OS patients than those in healthy controls. Circulating FGF19 levels strongly correlated with C4 (r=−0.695, p<0.0001), direct bilirubin (r=0.598, p=0.0001), and total bile acids (r=0.595, p=0.002). Moreover, circulating FGF19 levels strongly correlated with the model for end-stage liver disease score (r=0.574, p=0.0005) and Mayo risk score (r=0.578, p=0.001). Conclusions. Serum FGF19 is significantly increased in patients with PBC-AIH OS, while BA synthesis is suppressed. Circulating FGF19 primarily controls the regulation of BA synthesis in response to cholestasis and under cholestatic conditions. Therefore, modulation of circulating FGF19 could provide a promising targeted therapy for patients with PBC-AIH OS.

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Galectin-3 in Inflammasome Activation and Primary Biliary Cholangitis Development

International Journal of Molecular Sciences ◽

10.3390/ijms21145097 ◽

2020 ◽

Vol 21 (14) ◽

pp. 5097

Author(s):

Aleksandar Arsenijevic ◽

Bojana Stojanovic ◽

Jelena Milovanovic ◽

Dragana Arsenijevic ◽

Nebojsa Arsenijevic ◽

...

Keyword(s):

Nlrp3 Inflammasome ◽

Animal Studies ◽

Current Knowledge ◽

Specific Binding ◽

Primary Biliary Cholangitis ◽

Inflammasome Activation ◽

Multimeric Complex ◽

Galectin 3 ◽

Binding Lectin

Primary biliary cholangitis (PBC) is a chronic inflammatory autoimmune liver disease characterized by inflammation and damage of small bile ducts. The NLRP3 inflammasome is a multimeric complex of proteins that after activation with various stimuli initiates an inflammatory process. Increasing data obtained from animal studies implicate the role of NLRP3 inflammasome in the pathogenesis of various diseases. Galectin-3 is a β-galactoside-binding lectin that plays important roles in various biological processes including cell proliferation, differentiation, transformation and apoptosis, pre-mRNA splicing, inflammation, fibrosis and host defense. The multilineage immune response at various stages of PBC development includes the involvement of Gal-3 in the pathogenesis of this disease. The role of Galectin-3 in the specific binding to NLRP3, and inflammasome activation in models of primary biliary cholangitis has been recently described. This review provides a brief pathogenesis of PBC and discusses the current knowledge about the role of Gal-3 in NLRP3 activation and PBC development.

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P273 The role of multimodality imaging in the evaluation of arteritis

European Heart Journal - Cardiovascular Imaging ◽

10.1093/ehjci/jez319.130 ◽

2020 ◽

Vol 21 (Supplement_1) ◽

Author(s):

T M Matajira Chia ◽

M Castineira Busto ◽

M Cespon Fernandez ◽

B Gimena Reyes ◽

F Calvo Iglesias ◽

...

Keyword(s):

Antinuclear Antibodies ◽

Aortic Wall ◽

Multimodality Imaging ◽

Lateral Wall ◽

Ascending Aorta ◽

Iliac Arteries ◽

Positron Emission ◽

Nuclear Antigens ◽

Pet Ct

Abstract A 61-year-old man was admitted to the hospital with an atypical pain lumbar with oligoanuria. Other comorbidities were: arterial hypertension, diabetes mellitus and smoking .On examination the patient was comfortable at rest, with a heart rate of 89 b.p.m. and a blood pressure of 147/2 mmHg. Normal S1 and S2 heart sounds were present. There were no signs of heart failure present. Patients complained of pain in hypogastrium on palpation. Creatinine 2.33 mg / dL. PCR 72. The immunological studies were normal (including IgG and IgA serological levels, antinuclear antibodies, extractable nuclear antigens, anti-neutrophil cytoplasmic antibodies. An Body CT was performed, it shows mass that includes the ureters as well as the iliac arteries and parietal thickening in aorta wall. The positron emission tomography–computed tomography (PET CT) scans was performed that evidences pathological hypermetabolism that surrounds both primitive iliac arteries with maximum SUV 12 g / ml. Pathological hypermetabolism in ascending aorta until reaching arch with maximum SUV of 9.1 mg / ml compatible with periaortitis in the ascending aorta. A study was completed with retroperitoneal mass biopsy that showed areas of retroperitoneal fibrosis with predominantly lymphoplasmacytic areas. IgG4 / IgG> 40% , Obliterative involvement of small venules suggestive of IgG4 disease. A transthoracic echocardiogram was performed which showed normal biventricular function, absence of significant valvular disease and thickening of the aortic wall compatible with periaortitis. The patient started glucocorticoid therapy with favorable response. A PET CT control was performed that showed disappearing retroperitoneal masses around iliac vessels and disappearance of activity in lateral wall of aorta and decrease activity about ascendent aorta. DIAGNOSIS : IgG4 -related aortitis Abstract P273 Figure.

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Liver biopsy in primary biliary cholangitis: is sinusoidal fibrosis the missing key?

Journal of Clinical Pathology ◽

10.1136/jclinpath-2019-205958 ◽

2019 ◽

Vol 72 (10) ◽

pp. 669-676 ◽

Cited By ~ 1

Author(s):

Thomas Warnes ◽

Stephen Roberts ◽

Alexander Smith ◽

Najib Haboubi ◽

Raymond F McMahon

Keyword(s):

Liver Biopsy ◽

Clinical Outcomes ◽

Prognostic Value ◽

Staging System ◽

Primary Biliary Cholangitis ◽

Hepatic Decompensation ◽

Optimal Method ◽

Mayo Score ◽

Serum Aspartate Aminotransferase

AimsThe role of liver biopsy in primary biliary cholangitis (PBC) is controversial, as is the optimal method of histological assessment. We compared the Ludwig and Ishak systems and three components of the Japanese (Nakanuma) staging system to evaluate their clinical and biochemical correlations and prognostic value.MethodsWe reviewed biopsies from 106 patients with PBC, derived from a previous trial of colchicine therapy with 24–34 years’ follow-up, following which five clinical outcomes were evaluated: hepatic decompensation, cholestatic PBC death/liver transplant, portal hypertensive PBC death, all PBC deaths and overall survival.ResultsLudwig and Ishak stages correlated well with prognostically significant parameters, including serum bilirubin, and both Mayo and Child Scores. Serum aspartate aminotransferase correlated with interface hepatitis (IFH), and alkaline phosphatase with orcein deposition, bile duct (BD) loss and cholestasis. Ludwig correlated with all five clinical outcomes, while Ishak stage was only significantly correlated with two. While sinusoidal fibrosis, orcein deposition, BD loss and cholestasis all predicted hepatic death/transplant, after correction for Mayo Score, the only histological parameters predictive of clinical outcomes were IFH (associated with two) and sinusoidal fibrosis (associated with all five).ConclusionLiver biopsy is required in the diagnosis of around 20% of patients with PBC. The Ludwig system is of more prognostic value than both Ishak and any of the three individual components of the Nakanuma staging system, but the major histological parameter providing independent prognostic value beyond the Mayo Score is sinusoidal fibrosis.

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