Persistence of autoantibodies against recombinant mitochondrial and nuclear pore proteins after orthotopic liver transplantation for primary biliary cirrhosis

Alberto Mattalia, Birgit Lüttig, Floriano Rosina, Patrick S Leung, Judith A Van de Water, Marzia Bauducci, Alessia Ciancio, Klaus H W Böker, Howard Worman, Ross L. Cooper, Michael Manns, Aftab Ansari, Mario Rizzetto, M. Eric Gershwin

Research output: Contribution to journalArticle

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Abstract

Primary biliary cirrhosis is an autoimmune disease characterized by high titer autoantibodies predominantly against mitochondrial antigens PDC- E2, BCOADC-E2 and OGDC-E2. Currently orthotopic liver transplant (OLT) is the major form of treatment for end-stage primary biliary cirrhosis (PBC), but it is still unclear whether the autoimmune response continues posttransplantation. In this study we took advantage of a well-defined collection of sera collected serially before and after liver transplantation. We assayed these sera for quantitative and isotype- specific titers of antibodies against a set of recombinant mitochondrial autoantigens. We also studied reactivity to gp210. Serum samples were taken before transplantation and at intervals of 6 months, 1, 2, and 3 years after OLT. Before OLT 24/35 patients were AMA-positive, including seven out of the 35 to PDC-E2 alone, eight to both PDC-E2 and OGDC-E2, six to both PDC-E2 and BCOADC-E2, two to BCOADC-E2 alone and one to OGDC-E2. Following OLT, the frequency of sera that responded to PDC-E2 alone increased from seven to 12/35. Similarly, reactivity to BCOADC-E2 slightly increased from two to four out of 35. However, there was an overall decrease in sera that responded to more than one antigen. Neither Ig isotype nor subclass of the autoimmune response changed following OLT. Findings with gp210 were similar, in that reactivity to gp210 was found in nine out of 35 patients pre-OLT; following OLT the frequency decreased to seven out of 35 patients. Overall, the titers of AMAs decline slightly during the' first year post- OLT, but are equivalent to pre-OLT values by 6 months. Moreover, the antibody subclass/isotype remained unchanged. These data suggest that the removal of a diseased PBC liver has little, if any, impact on the serological characteristics of PBC. Moreover, it provides information regarding the natural history of PBC, particularly on the long latency time for disease development.

Original languageEnglish (US)
Pages (from-to)491-497
Number of pages7
JournalJournal of Autoimmunity
Volume10
Issue number5
DOIs
StatePublished - Oct 1997

Fingerprint

Nuclear Pore
Porins
Biliary Liver Cirrhosis
Nuclear Proteins
Liver Transplantation
Autoantibodies
dihydrolipoamide succinyltransferase
Transplants
Liver
Serum
Autoimmunity
Antibodies
Autoantigens
Autoimmune Diseases
Transplantation

Keywords

  • BCOADC-E2 branched chain alpha-keto acid dehydrogenase dihydrolipoamide acetyltransferase
  • OGDC-E2-oxoglutarate dehydrogenase complex
  • OLT orthotopic liver transplantation
  • PBC primary biliary cirrhosis
  • PDC-E2 pyruvate dehydrogenase complex

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Persistence of autoantibodies against recombinant mitochondrial and nuclear pore proteins after orthotopic liver transplantation for primary biliary cirrhosis. / Mattalia, Alberto; Lüttig, Birgit; Rosina, Floriano; Leung, Patrick S; Van de Water, Judith A; Bauducci, Marzia; Ciancio, Alessia; Böker, Klaus H W; Worman, Howard; Cooper, Ross L.; Manns, Michael; Ansari, Aftab; Rizzetto, Mario; Gershwin, M. Eric.

In: Journal of Autoimmunity, Vol. 10, No. 5, 10.1997, p. 491-497.

Research output: Contribution to journalArticle

Mattalia, Alberto ; Lüttig, Birgit ; Rosina, Floriano ; Leung, Patrick S ; Van de Water, Judith A ; Bauducci, Marzia ; Ciancio, Alessia ; Böker, Klaus H W ; Worman, Howard ; Cooper, Ross L. ; Manns, Michael ; Ansari, Aftab ; Rizzetto, Mario ; Gershwin, M. Eric. / Persistence of autoantibodies against recombinant mitochondrial and nuclear pore proteins after orthotopic liver transplantation for primary biliary cirrhosis. In: Journal of Autoimmunity. 1997 ; Vol. 10, No. 5. pp. 491-497.
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AU - Ciancio, Alessia

AU - Böker, Klaus H W

AU - Worman, Howard

AU - Cooper, Ross L.

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N2 - Primary biliary cirrhosis is an autoimmune disease characterized by high titer autoantibodies predominantly against mitochondrial antigens PDC- E2, BCOADC-E2 and OGDC-E2. Currently orthotopic liver transplant (OLT) is the major form of treatment for end-stage primary biliary cirrhosis (PBC), but it is still unclear whether the autoimmune response continues posttransplantation. In this study we took advantage of a well-defined collection of sera collected serially before and after liver transplantation. We assayed these sera for quantitative and isotype- specific titers of antibodies against a set of recombinant mitochondrial autoantigens. We also studied reactivity to gp210. Serum samples were taken before transplantation and at intervals of 6 months, 1, 2, and 3 years after OLT. Before OLT 24/35 patients were AMA-positive, including seven out of the 35 to PDC-E2 alone, eight to both PDC-E2 and OGDC-E2, six to both PDC-E2 and BCOADC-E2, two to BCOADC-E2 alone and one to OGDC-E2. Following OLT, the frequency of sera that responded to PDC-E2 alone increased from seven to 12/35. Similarly, reactivity to BCOADC-E2 slightly increased from two to four out of 35. However, there was an overall decrease in sera that responded to more than one antigen. Neither Ig isotype nor subclass of the autoimmune response changed following OLT. Findings with gp210 were similar, in that reactivity to gp210 was found in nine out of 35 patients pre-OLT; following OLT the frequency decreased to seven out of 35 patients. Overall, the titers of AMAs decline slightly during the' first year post- OLT, but are equivalent to pre-OLT values by 6 months. Moreover, the antibody subclass/isotype remained unchanged. These data suggest that the removal of a diseased PBC liver has little, if any, impact on the serological characteristics of PBC. Moreover, it provides information regarding the natural history of PBC, particularly on the long latency time for disease development.

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