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Outcome of intensive immunosuppression and autologous stem cell transplantation in patients with severe rheumatoid arthritis is associated with the composition of synovial T cell infiltration

Lookup NU author(s): Professor John IsaacsORCiD, Professor Jaap Van Laar


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Objective: To determine clinical and immunological correlates of high dose chemotherapy (HDC) + autologous stem cell transplantation (ASCT) in patients with severe rheumatoid arthritis (RA), refractory to conventional treatment. Methods: Serial samples of peripheral blood and synovial tissue were obtained from seven patients with RA treated with HDC and autologous peripheral blood grafts enriched for CD34+ cells. Disease activity was assessed with the Disease Activity Score (DAS), serum concentrations of C reactive protein (CRP), and human immunoglobulin (HIg) scans, and the extent of immunoablation was determined by immunophenotyping of peripheral blood mononuclear cells, and immunohistochemistry and double immunofluorescence of synovium. Results: Clinical responders (n = 5) had a larger number of cells at baseline expressing CD3, CD4, CD27, CD45RA, CD45RB, and CD45RO in synovium (p<0.05), higher activity on HIg scans (p = 0.08), and a trend towards higher concentrations of CRP in serum than non-responders (n = 2). Subsequent remissions and relapses in responders paralleled reduction and re-expression, respectively, of T cell markers. A relatively increased expression of CD45RB and CD45RO on synovial CD3 T cells was seen after HDC + ASCT. No correlations were found between DAS and changes in B cells or macrophage infiltration or synoviocytes. Conclusions: HDC + ASCT results in profound but incomplete immunoablation of both the memory and naìˆve T cell compartment, which is associated with longlasting clinical responses in most patients. The findings provide strong circumstantial evidence for a role of T cells in established RA, and demonstrate a role for the synovium in post-transplantation T cell reconstitution.

Publication metadata

Author(s): Verburg RJ, Flierman R, Sont JK, Ponchel F, Van Dreunen L, Levarht EW, Welling MM, Toes REM, Isaacs JD, Van Laar JM

Publication type: Article

Publication status: Published

Journal: Annals of the Rheumatic Diseases

Year: 2005

Volume: 64

Issue: 10

Pages: 1397-1405

ISSN (print): 0003-4967

ISSN (electronic): 1468-2060

Publisher: BMJ Group


DOI: 10.1136/ard.2004.033332

PubMed id: 15829573


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