Detection of retroviral antibodies in primary biliary cirrhosis and other idiopathic biliary disorders

Mason, Andrew L.; Xu, Lizhe; Guo, Li; Muñoz, Santiago J.; Jaspan, Jonathan B.; Bryer‐Ash, Michael; Cao, Yan; Sander, David M.; Shoenfeld, Yehuda; Ahmed, Ashfaq; Water, Judith A Van de; Gershwin, M. Eric; Garry, Robert F.

doi:10.1016/s0140-6736(97)10290-2

Cited by 152 publications

(92 citation statements)

References 16 publications

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“…For example, chronic hepatitis C viral infection is associated with LKM-3 autoantibodies. Mason et al 62 has reported the presence of retroviral antibodies in the serum of patients with PBC, but these are also found in patients with other cholestatic diseases. That AMA are primarily of the IgG3 and IgM isotype is also consistent with a viral infection.…”

Section: Is There An Infectious Trigger To Pbc?mentioning

confidence: 99%

PBC and AMA?what is the connection?

Neuberger

Thomson²

1999

Hepatology

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Primary Biliary Cirrhosis (PBC) is very closely associated with the presence of antimitochondrial antibodies (AMA); indeed, the presence of these antibodies is virtually disease specific. Despite the major advances made during the last decade in identifying the antigens with which these antibodies react, the reason for the close association remains uncertain. In this review, we examine the clinical correlates of AMA with features of PBC and discuss the possible implications of the association. CLINICAL CORRELATES Epidemiology of PBCThere is geographical variation in the prevalence of PBC, being highest in areas such as the north of England and parts of North America but rare in Africa and the Indian subcontinent. 1 Studies from the north of England suggest that the incidence of PBC is increasing. Clustering of cases is well described. 2 PBC may occur in families, and up to 4% of first-degree relatives may have PBC. Where PBC does occur in families, it may be related to maternally inherited factors and tends to present earlier in the second generation. 3 AMA Are Detectable Before the Clinical and Histological Features of PBCOf 29 asymptomatic patients who were found to have AMA in serum (later confirmed to be reactive with E2 components of pyruvate dehydrogenase) but with normal liver tests only two had normal liver histology. 4 A decade later, 76% had developed symptoms of PBC and 83% had cholestatic liver tests. None had progressed to cirrhosis. 5

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Section: Is There An Infectious Trigger To Pbc?mentioning

confidence: 99%

PBC and AMA?what is the connection?

Neuberger

Thomson²

1999

Hepatology

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“…and A.M., unpublished data) but found no evidence that these or other human endogenous retroviruses functioned as infectious agents in human autoimmune diseases (9,10). However, a report documenting the isolation a transmissible retrovirus from patients with Sjögren's syndrome (11), known as the human intracisternal A-type particle (HIAP), provided an impetus to study whether a similar etiology was applicable to PBC. To assess whether PBC patients had serologic evidence of an unrecognized retrovirus infection, we used HIAP proteins to show that 50% of patients with PBC were Western blot positive.…”

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confidence: 99%

Does a betaretrovirus infection trigger primary biliary cirrhosis?

Shen

Guo

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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216

246

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Patients with primary biliary cirrhosis develop progressive ductopenia associated with the production of antimitochondrial antibodies that react with a protein aberrantly expressed on biliary epithelial cells and peri-hepatic lymph nodes. Although no specific microbe has been identified, it is thought that an infectious agent triggers this autoimmune liver disease in genetically predisposed individuals. Previous serologic studies have provided evidence to suggest a viral association with primary biliary cirrhosis. Here we describe the identification of viral particles in biliary epithelium by electron microscopy and the cloning of exogenous retroviral nucleotide sequences from patients with primary biliary cirrhosis. The putative agent is referred to as the human betaretrovirus because it shares close homology with the murine mammary tumor virus and a human retrovirus cloned from breast cancer tissue. In vivo, we have found that the majority of patients with primary biliary cirrhosis have both RT-PCR and immunohistochemistry evidence of human betaretrovirus infection in lymph nodes. Moreover, the viral proteins colocalize to cells demonstrating aberrant autoantigen expression. In vitro, we have found that lymph node homogenates from patients with primary biliary cirrhosis can induce autoantigen expression in normal biliary epithelial cells in coculture. Normal biliary epithelial cells also develop the phenotypic manifestation of primary biliary cirrhosis when cocultivated in serial passage with supernatants containing the human betaretrovirus or the murine mammary tumor virus, providing a model to test Koch's postulates in vitro.

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“…3 As environmental factors, certain bacterial and viral infections, including Escherichia coli, mycobacteria, and a retrovirus, are reported to be involved. 4 To date, however, no specific virus has been implicated in the pathogenesis, although cases of PBC tend to cluster within areas.…”

Section: Frequent Detection Of Immunoglobulin M Anti-herpes Simplex Vmentioning

confidence: 99%

“…4 To date, however, no specific virus has been implicated in the pathogenesis, although cases of PBC tend to cluster within areas.Herpes simplex virus (HSV) is a hepatotropic virus, but it is an uncommon cause of hepatitis in immunocompetent adults. HSV hepatitis occurs in neonatal infections, pregnancy, and immunosuppressed patients.…”

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Frequent detection of immunoglobulin M anti-herpes simplex viral antibody in patients with primary biliary cirrhosis

Fujiwara

Yokosuka

2012

Hepatology

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We read with great interest the article by McNally et al., 1 who reported the involvement of a seasonally varying environmental agent in the etiology of primary biliary cirrhosis (PBC), and who have reported previously that a transient environmental agent may be involved in the etiology using a space-time clustering method among cases of PBC in a defined geographical population of northeast England. 2A combination of genetic predisposition and environmental factors are thought to contribute the etiology of PBC.3 As environmental factors, certain bacterial and viral infections, including Escherichia coli, mycobacteria, and a retrovirus, are reported to be involved. 4 To date, however, no specific virus has been implicated in the pathogenesis, although cases of PBC tend to cluster within areas.Herpes simplex virus (HSV) is a hepatotropic virus, but it is an uncommon cause of hepatitis in immunocompetent adults. HSV hepatitis occurs in neonatal infections, pregnancy, and immunosuppressed patients. Recently, we frequently detected immunoglobulin M (IgM) anti-HSV antibody in patients with PBC. Twenty-two (55%) of 40 patients were positive (cutoff index >1.2) for IgM anti-HSV, 13 (33%) were negative (<0.8), and five (12%) were undetermined (0.8-1.2) (Fig. 1). Nineteen of 22 patients with positive IgM anti-HSV were positive for immunoglobulin G (IgG) anti-HSV, and three were negative. Nine of 13 patients with negative IgM anti-HSV were positive for IgG anti-HSV, and four were negative. Four of five undetermined patients were positive for IgG anti-HSV, and one was negative. Nakamura et al. 5 reported that two different progression types exist in PBC and that positive anti-gp210 (antinuclear membrane) and positive anticentromere antibodies represent the hepatic failure type and portal hypertension type, respectively. All five patients with antinuclear membrane antibodies showed strong positivity (Fig. 1, arrows). Five of 13 patients with anticentromere antibodies showed weak positivity (Fig. 1, arrowheads).Our results support environmental factors involved in the etiology of PBC, although further studies should be done to evaluate whether HSV is an infectious agent or whether IgM anti-HSV is the result of a response to cross-reactive cellular proteins.

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Detection of retroviral antibodies in primary biliary cirrhosis and other idiopathic biliary disorders

Cited by 152 publications

References 16 publications

PBC and AMA?what is the connection?

PBC and AMA?what is the connection?

Does a betaretrovirus infection trigger primary biliary cirrhosis?

Frequent detection of immunoglobulin M anti-herpes simplex viral antibody in patients with primary biliary cirrhosis

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