Autotaxin, Pruritus and Primary Biliary Cholangitis (PBC)

Sun, Ying; Zhang, Weici; Evans, Jilly F.; Floreani, Annarosa; Zheng-sheng, Zou; Nishio, Yukiko; Qi, Ruizhao; Leung, Patrick S.C.; Bowlus, Christopher L.; Gershwin, M. Eric

doi:10.1016/j.autrev.2016.03.019

Cited by 31 publications

(41 citation statements)

References 67 publications

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“…In the cholestatic diseases, PBC and PSC bile acid metabolism contributes to the inflammation. Whereas PBC is characterized by the presence of highly specific autoantibodies reacting against PDC epitopes of the inner mitochondrial membrane, these antibodies do not seem to be pathogenic [211]. T cell epitopes have been identified for some of the diseases, such as PBC and type 2 (LKM-1 positive) AIH, but the relevant autoantigens are unknown for most patients, which represents a major unmet need impairing the development of specific treatment options.…”

Section: Immunological Backgroundmentioning

confidence: 97%

Immunology of hepatic diseases during pregnancy

2016

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The mother's immune system has to adapt to pregnancy accepting the semi-allograft fetus and preventing harmful effects to the developing child. Aberrations in feto-maternal immune adaptation may result in disease of the mother, such as liver injury. Five pregnancy-associated liver disorders have been described so far, however, little is known concerning immune alterations promoting the respective disease. These liver disorders are pre-eclampsia, hemolysis, elevated liver enzymes, low platelet count (HELLP), acute fatty liver, hyperemesis gravidarum, and intrahepatic cholestasis of pregnancy. On the other hand, pre-existing autoimmune liver injury of the mother can be affected by pregnancy. This review intends to summarize current knowledge linking feto-maternal immunology and liver inflammation with a special emphasis on novel potential biomarkers.

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Section: Immunological Backgroundmentioning

confidence: 97%

Immunology of hepatic diseases during pregnancy

2016

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“…Patients with PBC normally suffer from itching and fatigue, regardless of disease severity[14,37,38]. Serum fat-soluble vitamin D deficiency may be detected, particularly in advanced PBC patients[39,40].…”

Section: Risk Factorsmentioning

confidence: 99%

“…Pruritus is a pre-eminent symptom in PBC patients with chronic cholestasis and is variably reported in PBC characterized by cholestasis[9-11,14]. More than two-thirds of PBC patients experience pruritus during the process of the illness[9-11].…”

Section: Risk Factorsmentioning

confidence: 99%

“…The pathogenesis of cholestatic pruritus remains largely elusive[9-11]; its natural history, related pathogenesis, and molecular mechanisms are under continued investigation[9-11]. The autotaxin (ATX)-lysophosphatidic acid signaling axis may play a vital part in the nosogenesis of pruritus, and has lately has been connected with pruritus in PBC[14]. Several pieces of evidence have showed that a circulating pruritogen will take responsibility for it, but identification of the small molecule has yet to be ultimately identified[14].…”

Section: Risk Factorsmentioning

confidence: 99%

“…Moreover, in less-developed countries, the incidence of PBC might be less common[13]. Fatigue and pruritus are incipient clinical manifestations that appear in approximately 20% of PBC patients[14]. Although the clinical presentation and natural disease history of PBC patients have progressively improved over the years due to the recognition of earlier widespread use of ursodeoxycholic acid (UDCA), about 1/3 of PBC patients display suboptimal biochemical responses to UDCA and a poor prognosis[9-12].…”

Section: Introductionmentioning

confidence: 99%

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Recent advances in the diagnosis and treatment of primary biliary cholangitis

Huang¹

2016

WJH

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Primary biliary cholangitis (PBC), formerly referred to as primary biliary cirrhosis, is an infrequent progressive intrahepatic cholestatic autoimmune illness that can evolve into hepatic fibrosis, hepatic cirrhosis, hepatic failure, and, in some cases, hepatocellular carcinoma. The disease itself is characterized by T-lymphocyte-mediated chronic non-suppurative destructive cholangitis and elevated serum levels of extremely specific anti-mitochondrial autoantibodies (AMAs). In this article, we will not only review epidemiology, risk factors, natural history, predictive scores, radiologic approaches (e.g., acoustic radiation force impulse imaging, vibration controlled transient elastography, and magnetic resonance elastography), clinical features, serological characteristics covering biochemical markers, immunoglobulins, infections markers, biomarkers, predictive fibrosis marker, specific antibodies (including AMAs such as AMA-M2), anti-nuclear autoantibodies [such as anti-multiple nuclear dot autoantibodies (anti-sp100, PML, NDP52, anti-sp140), anti-rim-like/membranous anti-nuclear autoantibodies (anti-gp210, anti-p62), anti-centromere autoantibodies, and some of the novel autoantibodies], histopathological characteristics of PBC, diagnostic advances, and anti-diastole of PBC. Furthermore, this review emphasizes the recent advances in research of PBC in terms of therapies, including ursodeoxycholic acid, budesonide, methotrexate, obeticholic acid, cyclosporine A, fibrates such as bezafibrate and fenofibrate, rituximab, mesenchymal stem cells transplant, and hepatic transplant. Currently, hepatic transplant remains the only optimal choice with acknowledged treatment efficiency for end-stage PBC patients.

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Increased β‐endorphin and autotaxin in patients with prurigo

Ishikawa

Hashimoto

Munetsugu

et al. 2019

J Cutaneous Imm & Allergy

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This is an open access article under the terms of the Creat ive Commo ns Attri butio n-NonCo mmerc ial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. AbstractObjectives: Prurigo is a treatment-resistant inflammatory disease of unknown etiology. Persistent and severe itch is a major and important clinical symptom, but pathological mechanisms and/or actual mediators for itch in prurigo remain to be defined. Methods:We investigated blood levels of β-endorphin, dynorphin A, and autotaxin in adult patients with prurigo (n = 18), including prurigo nodularis, prurigo chronica multiformis, and other forms. Patients with hemodialysis, hepatic dysfunction, and pregnancy were excluded. Immunofluorescence staining for β-endorphin and autotaxin in lesional skin was also performed. In addition, β-endorphin and autotaxin synthesis of cultured epidermal keratinocytes in response to several cytokine stimulation was assessed in vitro.Results: Blood levels of β-endorphin were higher in patients with prurigo than in control subjects (n = 20), while dynorphin A levels were comparable in the two groups.Blood autotaxin levels also were increased in patients with prurigo compared to control subjects. On the one hand, epidermal expression of β-endorphin was increased in skin lesions of prurigo chronica multiformis, but not in prurigo nodularis. On the other hand, enhanced expression of autotaxin was observed in the epidermis in both prurigo nodularis and prurigo chronica multiformis. In vitro studies showed that βendorphin-expressing epidermal keratinocytes increased following stimulation with TNF-α, interleukin-31, and/or IFN-γ. Autotaxin was also detected in the cytoplasm of cultured epidermal keratinocytes. The fraction of autotaxin-expressing cells increased when stimulated with TNF-α and/or interleukin-31.Conclusions: Imbalance of opioid receptor signals and/or the autotaxin-lysophosphatidic acid axis may contribute, at least in part, to the pathogenesis and intractable pruritus in some of the patients with prurigo.

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Autotaxin, Pruritus and Primary Biliary Cholangitis (PBC)

Cited by 31 publications

References 67 publications

Immunology of hepatic diseases during pregnancy

Immunology of hepatic diseases during pregnancy

Recent advances in the diagnosis and treatment of primary biliary cholangitis

Increased β‐endorphin and autotaxin in patients with prurigo

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