Lack of immunological or molecular evidence for a role of mouse mammary tumor retrovirus in primary biliary cirrhosis

Carlo Selmi, Susan R. Ross, Aftab A. Ansari, Pietro Invernizzi, Mauro Podda, Ross L. Coppel, M. Eric Gershwin

Research output: Contribution to journalArticle

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Abstract

Background & Aims: Recent observations, including a pilot clinical trial, have suggested that a human mouse mammary tumor virus (MMTV) causes primary biliary cirrhosis (PBC). We attempted to confirm such data. Methods: We obtained sera from 101 patients (53 with PBC and 48 controls), fixed liver sections from 10 patients (8 PBC and 2 controls), fresh liver specimens (6 PBC and 6 controls), and fresh peripheral blood lymphocytes (PBLs) (10 PBC and 10 controls). We studied sera for reactivities against 3 different strains of MMTV virions, MMTV(C3H), MMTV(FM), and MMTV(LA), including goat polyclonal antibodies against MMTV virions, gp52, and p27 as positive controls. We stained liver specimens using polyclonal antibodies against MMTV and gp52 and further examined tissue samples and PBLs for specific MMTV genome sequences. Results: By Western blot analysis, no detectable reactivity in any of the PBC sera against any of the 3 MMTV strains or MMTV gp52 or p27 was observed. However, viral proteins were recognized by our control positive polyclonal antibodies. We note that 13%-60% of PBC sera presented low reactivity against 2 proteins of approximately 57 and 74 kilodaltons. Such reactivity is related to the trace amounts of mitochondrial antigens in the virus preparations derived from murine mammary tumor tissue. No detectable immunohistochemical or molecular evidence for MMTV was found in the liver specimens or PBLs. Conclusions: We were unable to recapitulate the data on this specific retroviral etiology of PBC and suggest that such data could be the result of contamination.

Original languageEnglish (US)
Pages (from-to)493-501
Number of pages9
JournalGastroenterology
Volume127
Issue number2
DOIs
StatePublished - Aug 2004

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Mouse mammary tumor virus
Biliary Liver Cirrhosis
Retroviridae
Breast Neoplasms
Liver
Lymphocytes
Serum
Virion
Antibodies
Inbred C3H Mouse
Viral Proteins
Goats
Western Blotting

Keywords

  • AMA
  • antimitochondrial antibodies
  • BEC
  • biliary epithelial cell
  • hTfR1
  • human transferrin receptor 1
  • MMTV
  • mouse mammary tumor virus
  • PBC
  • PBL
  • PCR
  • PDC-E2
  • peripheral blood lymphocyte
  • polymerase chain reaction
  • primary biliary cirrhosis

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Lack of immunological or molecular evidence for a role of mouse mammary tumor retrovirus in primary biliary cirrhosis. / Selmi, Carlo; Ross, Susan R.; Ansari, Aftab A.; Invernizzi, Pietro; Podda, Mauro; Coppel, Ross L.; Gershwin, M. Eric.

In: Gastroenterology, Vol. 127, No. 2, 08.2004, p. 493-501.

Research output: Contribution to journalArticle

Selmi, Carlo ; Ross, Susan R. ; Ansari, Aftab A. ; Invernizzi, Pietro ; Podda, Mauro ; Coppel, Ross L. ; Gershwin, M. Eric. / Lack of immunological or molecular evidence for a role of mouse mammary tumor retrovirus in primary biliary cirrhosis. In: Gastroenterology. 2004 ; Vol. 127, No. 2. pp. 493-501.
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abstract = "Background & Aims: Recent observations, including a pilot clinical trial, have suggested that a human mouse mammary tumor virus (MMTV) causes primary biliary cirrhosis (PBC). We attempted to confirm such data. Methods: We obtained sera from 101 patients (53 with PBC and 48 controls), fixed liver sections from 10 patients (8 PBC and 2 controls), fresh liver specimens (6 PBC and 6 controls), and fresh peripheral blood lymphocytes (PBLs) (10 PBC and 10 controls). We studied sera for reactivities against 3 different strains of MMTV virions, MMTV(C3H), MMTV(FM), and MMTV(LA), including goat polyclonal antibodies against MMTV virions, gp52, and p27 as positive controls. We stained liver specimens using polyclonal antibodies against MMTV and gp52 and further examined tissue samples and PBLs for specific MMTV genome sequences. Results: By Western blot analysis, no detectable reactivity in any of the PBC sera against any of the 3 MMTV strains or MMTV gp52 or p27 was observed. However, viral proteins were recognized by our control positive polyclonal antibodies. We note that 13{\%}-60{\%} of PBC sera presented low reactivity against 2 proteins of approximately 57 and 74 kilodaltons. Such reactivity is related to the trace amounts of mitochondrial antigens in the virus preparations derived from murine mammary tumor tissue. No detectable immunohistochemical or molecular evidence for MMTV was found in the liver specimens or PBLs. Conclusions: We were unable to recapitulate the data on this specific retroviral etiology of PBC and suggest that such data could be the result of contamination.",
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AU - Selmi, Carlo

AU - Ross, Susan R.

AU - Ansari, Aftab A.

AU - Invernizzi, Pietro

AU - Podda, Mauro

AU - Coppel, Ross L.

AU - Gershwin, M. Eric

PY - 2004/8

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N2 - Background & Aims: Recent observations, including a pilot clinical trial, have suggested that a human mouse mammary tumor virus (MMTV) causes primary biliary cirrhosis (PBC). We attempted to confirm such data. Methods: We obtained sera from 101 patients (53 with PBC and 48 controls), fixed liver sections from 10 patients (8 PBC and 2 controls), fresh liver specimens (6 PBC and 6 controls), and fresh peripheral blood lymphocytes (PBLs) (10 PBC and 10 controls). We studied sera for reactivities against 3 different strains of MMTV virions, MMTV(C3H), MMTV(FM), and MMTV(LA), including goat polyclonal antibodies against MMTV virions, gp52, and p27 as positive controls. We stained liver specimens using polyclonal antibodies against MMTV and gp52 and further examined tissue samples and PBLs for specific MMTV genome sequences. Results: By Western blot analysis, no detectable reactivity in any of the PBC sera against any of the 3 MMTV strains or MMTV gp52 or p27 was observed. However, viral proteins were recognized by our control positive polyclonal antibodies. We note that 13%-60% of PBC sera presented low reactivity against 2 proteins of approximately 57 and 74 kilodaltons. Such reactivity is related to the trace amounts of mitochondrial antigens in the virus preparations derived from murine mammary tumor tissue. No detectable immunohistochemical or molecular evidence for MMTV was found in the liver specimens or PBLs. Conclusions: We were unable to recapitulate the data on this specific retroviral etiology of PBC and suggest that such data could be the result of contamination.

AB - Background & Aims: Recent observations, including a pilot clinical trial, have suggested that a human mouse mammary tumor virus (MMTV) causes primary biliary cirrhosis (PBC). We attempted to confirm such data. Methods: We obtained sera from 101 patients (53 with PBC and 48 controls), fixed liver sections from 10 patients (8 PBC and 2 controls), fresh liver specimens (6 PBC and 6 controls), and fresh peripheral blood lymphocytes (PBLs) (10 PBC and 10 controls). We studied sera for reactivities against 3 different strains of MMTV virions, MMTV(C3H), MMTV(FM), and MMTV(LA), including goat polyclonal antibodies against MMTV virions, gp52, and p27 as positive controls. We stained liver specimens using polyclonal antibodies against MMTV and gp52 and further examined tissue samples and PBLs for specific MMTV genome sequences. Results: By Western blot analysis, no detectable reactivity in any of the PBC sera against any of the 3 MMTV strains or MMTV gp52 or p27 was observed. However, viral proteins were recognized by our control positive polyclonal antibodies. We note that 13%-60% of PBC sera presented low reactivity against 2 proteins of approximately 57 and 74 kilodaltons. Such reactivity is related to the trace amounts of mitochondrial antigens in the virus preparations derived from murine mammary tumor tissue. No detectable immunohistochemical or molecular evidence for MMTV was found in the liver specimens or PBLs. Conclusions: We were unable to recapitulate the data on this specific retroviral etiology of PBC and suggest that such data could be the result of contamination.

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KW - BEC

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KW - hTfR1

KW - human transferrin receptor 1

KW - MMTV

KW - mouse mammary tumor virus

KW - PBC

KW - PBL

KW - PCR

KW - PDC-E2

KW - peripheral blood lymphocyte

KW - polymerase chain reaction

KW - primary biliary cirrhosis

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DO - 10.1053/j.gastro.2004.05.033

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JO - Gastroenterology

JF - Gastroenterology

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