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Analysis of apoptosis in peripheral blood and synovial tissue very early after initiation of infliximab treatment in rheumatoid arthritis patients.
Arthritis Rheum. 2008 Nov; 58(11):3330-9.AR

Abstract

OBJECTIVE

Infliximab treatment results in a decrease in synovial cellularity as early as 48 hours after initiation of therapy in patients with rheumatoid arthritis (RA). This study was undertaken to investigate whether infliximab induces apoptosis within the first 24 hours after infusion.

METHODS

The percentage of apoptotic cells was determined by flow cytometry in blood drawn from 21 patients directly before, 1 hour after, and 24 hours after infliximab infusion. Synovial tissue samples obtained before, 1 hour after (n = 5), or 24 hours after (n = 5) initiation of therapy were subjected to immunohistochemistry to detect active caspase 3 and to TUNEL assay and electron microscopy to detect apoptosis. In addition, plasma levels of nucleosomes (generated during apoptosis) and C4b/c (an indicator of complement activation) were measured.

RESULTS

There were no signs of apoptosis induction in peripheral blood monocytes or lymphocytes after infliximab treatment. Circulating lymphocyte counts were increased within 1 hour after infusion (P < 0.05). There was no definite evidence of apoptosis induction in the synovium, except in 1 patient 24 hours after the infliximab infusion. Consistent with these results, there was no increase in nucleosome levels nor were there signs of complement activation.

CONCLUSION

Our findings indicate that the rapid decrease in synovial cellularity observed after initiation of anti-tumor necrosis factor antibody therapy cannot be explained by apoptosis induction at the site of inflammation. It is tempting to speculate that the striking effects on synovial inflammation may be explained by other mechanisms, such as decreased migration toward the synovial compartment and reduced retention in the inflamed synovium.

Authors+Show Affiliations

Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18975323

Citation

Wijbrandts, Carla A., et al. "Analysis of Apoptosis in Peripheral Blood and Synovial Tissue Very Early After Initiation of Infliximab Treatment in Rheumatoid Arthritis Patients." Arthritis and Rheumatism, vol. 58, no. 11, 2008, pp. 3330-9.
Wijbrandts CA, Remans PH, Klarenbeek PL, et al. Analysis of apoptosis in peripheral blood and synovial tissue very early after initiation of infliximab treatment in rheumatoid arthritis patients. Arthritis Rheum. 2008;58(11):3330-9.
Wijbrandts, C. A., Remans, P. H., Klarenbeek, P. L., Wouters, D., van den Bergh Weerman, M. A., Smeets, T. J., Vervoordeldonk, M. J., Baeten, D., & Tak, P. P. (2008). Analysis of apoptosis in peripheral blood and synovial tissue very early after initiation of infliximab treatment in rheumatoid arthritis patients. Arthritis and Rheumatism, 58(11), 3330-9. https://doi.org/10.1002/art.23989
Wijbrandts CA, et al. Analysis of Apoptosis in Peripheral Blood and Synovial Tissue Very Early After Initiation of Infliximab Treatment in Rheumatoid Arthritis Patients. Arthritis Rheum. 2008;58(11):3330-9. PubMed PMID: 18975323.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Analysis of apoptosis in peripheral blood and synovial tissue very early after initiation of infliximab treatment in rheumatoid arthritis patients. AU - Wijbrandts,Carla A, AU - Remans,Philip H, AU - Klarenbeek,Paul L, AU - Wouters,Diana, AU - van den Bergh Weerman,Marius A, AU - Smeets,Tom J, AU - Vervoordeldonk,Margriet J, AU - Baeten,Dominique, AU - Tak,Paul P, PY - 2008/11/1/pubmed PY - 2009/1/8/medline PY - 2008/11/1/entrez SP - 3330 EP - 9 JF - Arthritis and rheumatism JO - Arthritis Rheum VL - 58 IS - 11 N2 - OBJECTIVE: Infliximab treatment results in a decrease in synovial cellularity as early as 48 hours after initiation of therapy in patients with rheumatoid arthritis (RA). This study was undertaken to investigate whether infliximab induces apoptosis within the first 24 hours after infusion. METHODS: The percentage of apoptotic cells was determined by flow cytometry in blood drawn from 21 patients directly before, 1 hour after, and 24 hours after infliximab infusion. Synovial tissue samples obtained before, 1 hour after (n = 5), or 24 hours after (n = 5) initiation of therapy were subjected to immunohistochemistry to detect active caspase 3 and to TUNEL assay and electron microscopy to detect apoptosis. In addition, plasma levels of nucleosomes (generated during apoptosis) and C4b/c (an indicator of complement activation) were measured. RESULTS: There were no signs of apoptosis induction in peripheral blood monocytes or lymphocytes after infliximab treatment. Circulating lymphocyte counts were increased within 1 hour after infusion (P < 0.05). There was no definite evidence of apoptosis induction in the synovium, except in 1 patient 24 hours after the infliximab infusion. Consistent with these results, there was no increase in nucleosome levels nor were there signs of complement activation. CONCLUSION: Our findings indicate that the rapid decrease in synovial cellularity observed after initiation of anti-tumor necrosis factor antibody therapy cannot be explained by apoptosis induction at the site of inflammation. It is tempting to speculate that the striking effects on synovial inflammation may be explained by other mechanisms, such as decreased migration toward the synovial compartment and reduced retention in the inflamed synovium. SN - 0004-3591 UR - https://www.unboundmedicine.com/medline/citation/18975323/Analysis_of_apoptosis_in_peripheral_blood_and_synovial_tissue_very_early_after_initiation_of_infliximab_treatment_in_rheumatoid_arthritis_patients_ L2 - https://doi.org/10.1002/art.23989 DB - PRIME DP - Unbound Medicine ER -