Anti-PAD4 autoantibodies in rheumatoid arthritis: levels in serum over time and impact on PAD4 activity as measured with a small synthetic substrate
Abstract Isoform 4 of the human peptidylarginine deiminase (hPAD4) enzyme may be responsible for the citrullination of antigens in rheumatoid arthritis (RA) and has been shown to be itself the target of disease-specific autoantibodies. Here, we have tested whether the level of serum anti-hPAD4 antibodies in RA patients is stable over a period of 10 years and whether the antibodies influence hPAD4-mediated deimination of the small substrate N-α-Benzoyl-l-arginine ethyl ester. RA sera (n = 128) obtained at baseline and after 10 years were assessed for anti-hPAD4 antibodies by a specific immunoassay. For 118 RA patients, serum anti-hPAD4 IgG levels were stable over 10 years. Seven patients who were negative for anti-PAD4 IgG at baseline had become positive after 10 years. Further, total IgG from selected RA patients and controls were purified, and a fraction was depleted for anti-hPAD4 antibodies. Kinetic deimination assays were performed with total IgG and depleted fractions. The kcat and Km values of hPAD4-mediated deimination of N-α-Benzoyl-l-arginine ethyl ester were not affected by the depletion of the anti-hPAD4 antibodies from the total IgG pool. In conclusion, RA patients remain positive for anti-hPAD4 antibodies over time and some patients who are initially anti-hPAD4 negative become positive later in the disease course. The anti-hPAD4 antibodies did not affect the enzymatic activity of hPAD4 when the small substrate N-α-Benzoyl-l-arginine ethyl ester was used. However, this finding may not exclude an effect of these autoantibodies on citrullination of protein substrates in RA..
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2011 |
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| Erschienen: |
2011 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:32 |
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| Enthalten in: |
Rheumatology international - 32(2011), 5 vom: 26. Jan., Seite 1271-1276 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Pollmann, Sylvie [VerfasserIn] |
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| Links: |
Volltext [lizenzpflichtig] |
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| Themen: |
Autoantibodies |
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| Anmerkungen: |
© The Author(s) 2011 |
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| doi: |
10.1007/s00296-010-1765-y |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Anti-PAD4 autoantibodies in rheumatoid arthritis: levels in serum over time and impact on PAD4 activity as measured with a small synthetic substrate |
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| 520 | |a Abstract Isoform 4 of the human peptidylarginine deiminase (hPAD4) enzyme may be responsible for the citrullination of antigens in rheumatoid arthritis (RA) and has been shown to be itself the target of disease-specific autoantibodies. Here, we have tested whether the level of serum anti-hPAD4 antibodies in RA patients is stable over a period of 10 years and whether the antibodies influence hPAD4-mediated deimination of the small substrate N-α-Benzoyl-l-arginine ethyl ester. RA sera (n = 128) obtained at baseline and after 10 years were assessed for anti-hPAD4 antibodies by a specific immunoassay. For 118 RA patients, serum anti-hPAD4 IgG levels were stable over 10 years. Seven patients who were negative for anti-PAD4 IgG at baseline had become positive after 10 years. Further, total IgG from selected RA patients and controls were purified, and a fraction was depleted for anti-hPAD4 antibodies. Kinetic deimination assays were performed with total IgG and depleted fractions. The kcat and Km values of hPAD4-mediated deimination of N-α-Benzoyl-l-arginine ethyl ester were not affected by the depletion of the anti-hPAD4 antibodies from the total IgG pool. In conclusion, RA patients remain positive for anti-hPAD4 antibodies over time and some patients who are initially anti-hPAD4 negative become positive later in the disease course. The anti-hPAD4 antibodies did not affect the enzymatic activity of hPAD4 when the small substrate N-α-Benzoyl-l-arginine ethyl ester was used. However, this finding may not exclude an effect of these autoantibodies on citrullination of protein substrates in RA. | ||
| 650 | 4 | |a Rheumatoid arthritis | |
| 650 | 4 | |a Peptidylarginine deiminase 4 | |
| 650 | 4 | |a Citrulline | |
| 650 | 4 | |a Autoantibodies | |
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| 700 | 1 | |a Halvorsen, Eirik Hornes |4 aut | |
| 700 | 1 | |a Sollid, Ludvig M. |4 aut | |
| 700 | 1 | |a Kvien, Tore K. |4 aut | |
| 700 | 1 | |a Fleckenstein, Burkhard |4 aut | |
| 700 | 1 | |a Molberg, Øyvind |4 aut | |
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