Indeed, the demonstration of superantigen activity has been the standard for detecting MMTV contamination in mice because PCR cannot distinguish genomic viral RNA from endogenously-expressed MMTV transcripts, and mice infected by breast milk have suboptimal neutralizing antibody responses [78,82]. antimitochondrial antibody expression. Subsequently, we have derived layers of proof to support the role of betaretrovirus contamination in mouse models of autoimmune biliary disease with spontaneous AMA production and in patients with PBC. Using Hills criteria, we provide an overview of how betaretrovirus contamination may trigger autoimmunity and propagate biliary disease. Ultimately, the demonstration that disease can be cured with antiviral therapy may sway the argument toward an infectious disease etiology in an analogous fashion that Letermovir was used to link with peptic ulcer disease. Keywords: biliary epithelial cells (BEC), Bradford Hill criteria, human betaretrovirus (HBRV), Kochs postulates, mouse mammary tumor computer virus (MMTV), main biliary cholangitis (PBC) 1. Introduction 1.1. Main Biliary Cholangitis Main biliary cholangitis (PBC) is usually a rare cholestatic liver disease characterized by immune damage to intrahepatic bile ducts that may progress to cirrhosis and liver failure [1,2]. PBC is usually classified as an autoimmune disease because most patients (80C95%) make antimitochondrial antibodies (AMA) [1,2]. It is often assumed that PBC is usually caused by the autoimmune response, but the etiology of the disease is unknown [3]. PBC is usually diagnosed when patients present with elevated alkaline phosphatase, a positive serum AMA, or by liver biopsy in AMA-negative patients [1,2]. The target of AMA is usually pyruvate dehydrogenase E2 Letermovir protein (PDC-E2) that is overexpressed around the cell surface of biliary epithelium cells (BEC) and in perihepatic lymph nodes [4,5]. It is thought that the aberrant expression of PDC-E2 then prospects to the production of AMA and autoimmunity [4,5]. Genome-wide association studies have recognized genes linked with PBC, and epidemiological studies strongly suggest that environmental factors may trigger disease in genetically susceptible individuals [6]. Bacteria or exposure to xenobiotics have been proposed as external triggers, and we have focused on the role of human betaretrovirus (HBRV) contamination [7]. 1.2. PBC: Epidemiology and Pathophysiology Much like other autoimmune disorders, PBC is usually ~10 times more common in women [2]. Hormone replacement therapy and a more youthful age of first pregnancy both provide an increased risk of developing PBC [1,2]. PBC is usually a rare disease found in all parts of the world, with a prevalence ranging from 1:2500 to 1 1:100,000. There is an increased prevalence moving away from the equator, with geographical clustering in areas of North America and Europe. Indigenous Canadians have a markedly elevated prevalence of PBC and a worse prognosis compared with Canadians of European descent [8,9,10]. We will return to the model of how this may be linked with an increased burden of genetic predisposition and exposure to European-derived pathogens [11]. Histologically, patients develop non-suppurative cholangitis with the immune destruction of interlobular bile ducts. The progressive ductopenia leads to bile accumulation, resulting in fibrosis and cirrhosis. Therefore, choleretics are the mainstay of treatment, but they are not curative. In fact, patients unresponsive to the standard of care account for 5% of patients awaiting liver transplantation in North America [12]. PBC patients suffer from fatigue comparable with chronic fatigue syndrome/myalgic encephalomyelitis [13,14]. Some Letermovir of the exhaustion has a peripheral etiology, as PBC patients experience prolonged muscular acidosis with a slower rate of recovery of phosphocreatine levels following exercise [13,15]. The cause of fatigue is unknown but may persist in up to 50% of patients following liver transplantation despite having no apparent liver disease [16,17]. 1.3. PBC: Genes Rabbit polyclonal to ZNF43 vs. Environment Genetic factors are involved in the development of PBC. The disease occurs more frequently in Letermovir monozygotic versus dizygotic twins and is more common.
Recent Posts
- The complete sequence of hepatitis E virus genotype 4 reveals an alternative strategy for translation of open reading frames 2 and 3
- different from control *Significantly; not the same as control and from 1 and 14 days **significantly; not the same as pretarsal control #significantly
- We thank W
- The significance from the differences in immune responses for these viruses, furthermore to any differences in the consequences of molecular mimicry can’t be dependant on our study
- Methods Virol
Recent Comments
Archives
- February 2025
- January 2025
- December 2024
- November 2024
- October 2024
- September 2024
- May 2023
- April 2023
- March 2023
- February 2023
- January 2023
- December 2022
- November 2022
- October 2022
- September 2022
- August 2022
- July 2022
- June 2022
- May 2022
- April 2022
- March 2022
- February 2022
- January 2022
- December 2021
- November 2021
- October 2021
- September 2021
- August 2021
- July 2021
Categories
- Orexin Receptors
- Orexin, Non-Selective
- Orexin1 Receptors
- ORL1 Receptors
- Ornithine Decarboxylase
- Orphan 7-TM Receptors
- Orphan 7-Transmembrane Receptors
- Orphan G-Protein-Coupled Receptors
- Orphan GPCRs
- OT Receptors
- Other Acetylcholine
- Other Adenosine
- Other Apoptosis
- Other ATPases
- Other Calcium Channels
- Other Cannabinoids
- Other Channel Modulators
- Other Dehydrogenases
- Other Hydrolases
- Other Ion Pumps/Transporters
- Other Kinases
- Other MAPK
- Other Nitric Oxide
- Other Nuclear Receptors
- Other Oxygenases/Oxidases
- Other Peptide Receptors
- Other Pharmacology
- Other Product Types
- Other Proteases
- Other RTKs
- Other Synthases/Synthetases
- Other Tachykinin
- Other Transcription Factors
- Other Transferases
- Other Wnt Signaling
- OX1 Receptors
- OXE Receptors
- Oxidative Phosphorylation
- Oxoeicosanoid receptors
- Oxygenases/Oxidases
- Oxytocin Receptors
- P-Glycoprotein
- P-Selectin
- P-Type ATPase
- P-Type Calcium Channels
- p14ARF
- p160ROCK
- P2X Receptors
- P2Y Receptors
- p38 MAPK
- p53
- p56lck
- p60c-src
- p70 S6K
- p75
- p90 Ribosomal S6 Kinase
- PAC1 Receptors
- PACAP Receptors
- PAF Receptors
- PAO
- PAR Receptors
- Parathyroid Hormone Receptors
- PARP
- PC-PLC
- PDE
- PDGFR
- PDK1
- PDPK1
- Peptide Receptor, Other
- Peptide Receptors
- Peroxisome-Proliferating Receptors
- PGF
- PGI2
- Phosphatases
- Phosphodiesterases
- Phosphoinositide 3-Kinase
- Phosphoinositide-Specific Phospholipase C
- Phospholipase A
- Phospholipase C
- Phospholipases
- Phosphorylases
- Photolysis
- PI 3-Kinase
- PI 3-Kinase/Akt Signaling
- PI-PLC
- PI3K
- Pim Kinase
- Pim-1
- PIP2
- Pituitary Adenylate Cyclase Activating Peptide Receptors
- PKA
- PKB
- PKC
- PKD
- PKG
- PKM
- PKMTs
- PLA
- Plasmin
- Platelet Derived Growth Factor Receptors
- Platelet-Activating Factor (PAF) Receptors
- Uncategorized