PDC-E3BP is not a dominant T-cell autoantigen in primary biliary cirrhosis
BACKGROUND: Autoantibody responses reactive with the E2 and E3BP components of pyruvate dehydrogenase complex (PDC), which characterise primary biliary cirrhosis (PBC) crossreact, precluding the identification, from serological studies, of the antigen to which the principal breakdown of tolerance occurs. Although autoreactive T-cell responses to PDC-E2 have been well characterised it is, at present, unclear whether T-cell tolerance breakdown also occurs to PDC-E3BP. The aims of this study were to characterise autoreactive T-cell responses to PDC-E3BP in PBC and potential factors regulating their expression.
METHODS: Peripheral blood T-cell proliferative responses to purified recombinant human PDC-E2 and PDC-E3BP at a range of concentrations were characterised in PBC patients and control subjects.
RESULTS: T-cell proliferative responses to both E2 and E3BP were absent from control subjects (median peak stimulation index (SI) to PDC-E2 1.2 [range 0.3-1.9], 0/10 positive (SI>2.32), median peak SI to PDC-E3BP 1.1 [0.7-2.1]], 0/10 positive). Significant responses to PDC-E2 were seen in the majority of patients (median peak SI 11.4 [0.4-24.4], 17/20 (85%) positive) but to PDC-E3BP in only a minority (median peak SI 1-9 [0.6-9.95], 8/20 (40%) positive). Where responses to PDC-E3BP were seen they were universally secondary to responses to PDC-E2.
CONCLUSIONS: Despite the presence of antibodies reactive with PDC-E3BP in the majority of PBC patients this self-protein is not a dominant T-cell autoantigen in PBC.
Errataetall: | |
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Medienart: |
Artikel |
Erscheinungsjahr: |
2006 |
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Erschienen: |
2006 |
Enthalten in: |
Zur Gesamtaufnahme - volume:26 |
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Enthalten in: |
Liver international : official journal of the International Association for the Study of the Liver - 26(2006), 4 vom: 15. Mai, Seite 406-13 |
Sprache: |
Englisch |
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Beteiligte Personen: |
McHugh, Anna [VerfasserIn] |
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Anmerkungen: |
Date Completed 15.09.2006 Date Revised 15.11.2006 published: Print CommentIn: Liver Int. 2006 Aug;26(6):633-5. - PMID 16842317 Citation Status MEDLINE |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM162150245 |
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100 | 1 | |a McHugh, Anna |e verfasserin |4 aut | |
245 | 1 | 0 | |a PDC-E3BP is not a dominant T-cell autoantigen in primary biliary cirrhosis |
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500 | |a published: Print | ||
500 | |a CommentIn: Liver Int. 2006 Aug;26(6):633-5. - PMID 16842317 | ||
500 | |a Citation Status MEDLINE | ||
520 | |a BACKGROUND: Autoantibody responses reactive with the E2 and E3BP components of pyruvate dehydrogenase complex (PDC), which characterise primary biliary cirrhosis (PBC) crossreact, precluding the identification, from serological studies, of the antigen to which the principal breakdown of tolerance occurs. Although autoreactive T-cell responses to PDC-E2 have been well characterised it is, at present, unclear whether T-cell tolerance breakdown also occurs to PDC-E3BP. The aims of this study were to characterise autoreactive T-cell responses to PDC-E3BP in PBC and potential factors regulating their expression | ||
520 | |a METHODS: Peripheral blood T-cell proliferative responses to purified recombinant human PDC-E2 and PDC-E3BP at a range of concentrations were characterised in PBC patients and control subjects | ||
520 | |a RESULTS: T-cell proliferative responses to both E2 and E3BP were absent from control subjects (median peak stimulation index (SI) to PDC-E2 1.2 [range 0.3-1.9], 0/10 positive (SI>2.32), median peak SI to PDC-E3BP 1.1 [0.7-2.1]], 0/10 positive). Significant responses to PDC-E2 were seen in the majority of patients (median peak SI 11.4 [0.4-24.4], 17/20 (85%) positive) but to PDC-E3BP in only a minority (median peak SI 1-9 [0.6-9.95], 8/20 (40%) positive). Where responses to PDC-E3BP were seen they were universally secondary to responses to PDC-E2 | ||
520 | |a CONCLUSIONS: Despite the presence of antibodies reactive with PDC-E3BP in the majority of PBC patients this self-protein is not a dominant T-cell autoantigen in PBC | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
650 | 7 | |a Autoantigens |2 NLM | |
650 | 7 | |a Mitochondrial Proteins |2 NLM | |
650 | 7 | |a PDHX protein, human |2 NLM | |
650 | 7 | |a Pyruvate Dehydrogenase Complex |2 NLM | |
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700 | 1 | |a Robe, Amanda J |e verfasserin |4 aut | |
700 | 1 | |a Palmer, Jeremy M |e verfasserin |4 aut | |
700 | 1 | |a Jones, David E J |e verfasserin |4 aut | |
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