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Antinuclear antibodies following infliximab treatment in patients with rheumatoid arthritis or spondylarthropathy

Leen De Rycke, Elli Kruithof, Nancy Van Damme UGent, Ilse Hoffman, N VAN DEN BOSSCHE, Filip Van den Bosch UGent, Eric Veys UGent and Filip De Keyser UGent (2003) ARTHRITIS AND RHEUMATISM. 48(4). p.1015-1023
abstract
Objective. To investigate the effect of infliximab treatment on antinuclear antibodies (ANAs), anti-double-stranded DNA (anti-dsDNA), antinucleosome, antihistone, and anti-extractable nuclear antigen (anti-ENA) antibodies in rheumatoid arthritis (RA) and spondylarthropathy (SpA) patients. Methods. Sera from 62 RA and 35 SpA patients treated with infliximab were tested at baseline and week 30 (RA group) or week 34 (SpA group). ANAs were tested by indirect immunofluorescence (IIF) on HEp-2 cells. Anti-dsDNA antibodies were detected by IIF on Crithidia luciliae and by enzyme-linked immunosorbent assay (ELISA) and were further isotyped with gamma, mu, and a chain-specific conjugates at various time points. Antinucleosome antibodies were tested by ELISA. Anti-histone and anti-ENA antibodies were detected by line immunoassay. Results. Initially, 32 of 62 RA patients and 6 of 35 SpA patients tested positive for ANAs. After infliximab treatment, these numbers shifted to 51 of 62 (P < 0.001) and 31 of 35 (P < 0.001), respectively. At baseline, none of the RA or SpA patients had anti-dsDNA antibodies. After infliximab treatment, 7 RA patients (P = 0.016) and 6 SpA patients (P = 0.031) became positive for anti-dsDNA antibodies. All 7 anti-dsDNA-positive RA patients had IgM and IgA anti-dsDNA antibodies. Three of the 6 anti-dsDNA-positive SpA patients had IgM and IgA anti-dsDNA antibodies, and 2 had IgM anti-dsDNA antibodies alone. In both diseases, the IgM anti-dsDNA antibodies appeared before the IgA anti-dsDNA antibodies. During the observation period, no IgG anti-dsDNA antibodies or lupus symptoms were observed. The development of antinucleosome, antihistone, or anti-ENA antibodies following infliximab treatment was observed in some patients, but the numbers were not statistically significant. Conclusion. Infliximab treatment may induce ANAs, and especially IgM and IgA anti-dsDNA antibodies, in RA and SpA patients. However, no anti-dsDNA IgG antibodies or lupus symptoms were observed during the period of observation in this study, and the development of antinucleosome, antihistone, or anti-ENA antibodies was not statistically significant. These observations do not exclude potential induction of clinically significant lupus in the long term, and further followup is therefore mandatory.
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author
organization
year
type
journalArticle
publication status
published
subject
keyword
SYSTEMIC-LUPUS-ERYTHEMATOSUS, NECROSIS-FACTOR-ALPHA, CHIMERIC MONOCLONAL-ANTIBODY, ACTIVE ANKYLOSING-SPONDYLITIS, ETANERCEPT THERAPY, CROHNS-DISEASE, RECEIVING METHOTREXATE, REVISED CRITERIA, DSDNA ANTIBODIES, DNA ANTIBODIES
journal title
ARTHRITIS AND RHEUMATISM
Arthritis Rheum.
volume
48
issue
4
pages
1015-1023 pages
Web of Science type
Article
Web of Science id
000182115300017
JCR category
RHEUMATOLOGY
JCR impact factor
7.19 (2003)
JCR rank
1/21 (2003)
JCR quartile
1 (2003)
ISSN
0004-3591
language
English
UGent publication?
yes
classification
A1
id
209247
handle
http://hdl.handle.net/1854/LU-209247
date created
2004-04-07 14:26:00
date last changed
2010-08-13 13:48:03
@article{209247,
  abstract     = {Objective. To investigate the effect of infliximab  treatment on antinuclear  antibodies (ANAs), anti-double-stranded DNA (anti-dsDNA), antinucleosome, antihistone, and anti-extractable nuclear antigen (anti-ENA) antibodies in rheumatoid arthritis  (RA) and spondylarthropathy (SpA) patients.

Methods. Sera from 62 RA and 35 SpA patients treated with infliximab were tested at baseline and week 30 (RA group) or week 34 (SpA group). ANAs were tested by indirect immunofluorescence (IIF) on HEp-2 cells. Anti-dsDNA antibodies were detected by IIF on Crithidia luciliae and by enzyme-linked immunosorbent assay (ELISA) and were further isotyped with gamma, mu, and a chain-specific conjugates at various time points. Antinucleosome antibodies were tested by ELISA. Anti-histone and anti-ENA antibodies were detected by line immunoassay.

Results. Initially, 32 of 62 RA patients and 6 of 35 SpA patients tested positive for ANAs. After infliximab treatment, these numbers shifted to 51 of 62 (P {\textlangle} 0.001) and 31 of 35 (P {\textlangle} 0.001), respectively. At baseline, none of the RA or SpA patients had anti-dsDNA antibodies. After infliximab treatment, 7 RA patients (P = 0.016) and 6 SpA patients (P = 0.031) became positive for anti-dsDNA antibodies. All 7 anti-dsDNA-positive RA patients had IgM and IgA anti-dsDNA antibodies. Three of the 6 anti-dsDNA-positive SpA patients had IgM and IgA anti-dsDNA antibodies, and 2 had IgM anti-dsDNA antibodies alone. In both diseases, the IgM anti-dsDNA antibodies appeared before the IgA anti-dsDNA antibodies. During the observation period, no IgG anti-dsDNA antibodies or lupus symptoms were observed. The development of antinucleosome, antihistone, or anti-ENA antibodies following infliximab treatment was observed in some patients, but the numbers were not statistically significant.

Conclusion. Infliximab treatment may induce ANAs, and especially IgM and IgA anti-dsDNA antibodies, in RA and SpA patients. However, no anti-dsDNA IgG antibodies or lupus symptoms were observed during the period of observation in this study, and the development of antinucleosome, antihistone, or anti-ENA antibodies was not statistically significant. These observations do not exclude potential induction of clinically significant lupus in the long term, and further followup is therefore mandatory.},
  author       = {De Rycke, Leen and Kruithof, Elli and Van Damme, Nancy and Hoffman, Ilse and VAN DEN BOSSCHE, N and Van den Bosch, Filip and Veys, Eric and De Keyser, Filip},
  issn         = {0004-3591},
  journal      = {ARTHRITIS AND RHEUMATISM},
  keyword      = {SYSTEMIC-LUPUS-ERYTHEMATOSUS,NECROSIS-FACTOR-ALPHA,CHIMERIC MONOCLONAL-ANTIBODY,ACTIVE ANKYLOSING-SPONDYLITIS,ETANERCEPT THERAPY,CROHNS-DISEASE,RECEIVING METHOTREXATE,REVISED CRITERIA,DSDNA ANTIBODIES,DNA ANTIBODIES},
  language     = {eng},
  number       = {4},
  pages        = {1015--1023},
  title        = {Antinuclear antibodies following infliximab treatment in patients with rheumatoid arthritis or spondylarthropathy},
  volume       = {48},
  year         = {2003},
}

Chicago
De Rycke, Leen, Elli Kruithof, Nancy Van Damme, Ilse Hoffman, N VAN DEN BOSSCHE, Filip Van den Bosch, Eric Veys, and Filip De Keyser. 2003. “Antinuclear Antibodies Following Infliximab Treatment in Patients with Rheumatoid Arthritis or Spondylarthropathy.” Arthritis and Rheumatism 48 (4): 1015–1023.
APA
De Rycke, Leen, Kruithof, E., Van Damme, N., Hoffman, I., VAN DEN BOSSCHE, N., Van den Bosch, F., Veys, E., et al. (2003). Antinuclear antibodies following infliximab treatment in patients with rheumatoid arthritis or spondylarthropathy. ARTHRITIS AND RHEUMATISM, 48(4), 1015–1023.
Vancouver
1.
De Rycke L, Kruithof E, Van Damme N, Hoffman I, VAN DEN BOSSCHE N, Van den Bosch F, et al. Antinuclear antibodies following infliximab treatment in patients with rheumatoid arthritis or spondylarthropathy. ARTHRITIS AND RHEUMATISM. 2003;48(4):1015–23.
MLA
De Rycke, Leen, Elli Kruithof, Nancy Van Damme, et al. “Antinuclear Antibodies Following Infliximab Treatment in Patients with Rheumatoid Arthritis or Spondylarthropathy.” ARTHRITIS AND RHEUMATISM 48.4 (2003): 1015–1023. Print.