RESEARCH - The Outcome of Intensive Immunosuppression and Autologous Stemcell Transplantation in RA is Associated with the Composition of Synovial T Cell Infiltration.

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Ann Rheum Dis. 2005 Apr 13; [Epub ahead of print]

The Outcome of Intensive Immunosuppression and Autologous Stemcell

Transplantation in Patients with Severe Rheumatoid Arthritis is Associated

with the Composition of Synovial T Cell Infiltration.

Verburg R, Flierman R, Sont J, Ponchel F, van Dreunen L, Levahrt N, Welling

M, Toes R, Isaacs J, van Laar JM.

Leiden University Medical Center, Netherlands.

OBJECTIVE: High dose chemotherapy (HDC) followed by autologous stem cell

transplantation (ASCT) is an experimental treatment modality for patients

with severe autoimmune diseases including refractory rheumatoid arthritis

(RA). It is aimed at immunoablation to allow regeneration of a non-

autoaggressive immune system from reinfused stem cells. This study was

undertaken to determine clinical and immunological correlates of HDC + ASCT

in patients with severe rheumatoid arthritis (RA), refractory to

conventional therapy. METHODS: Seven RA patients treated with HDC and

autologous peripheral blood grafts enriched for CD34+ cells underwent serial

sampling of peripheral blood and synovial tissue specimens. Disease activity

was assessed with disease activity scores (DAS), serum concentrations of

C-reactive protein (CRP) , and human immunoglobulin (HIG)-scans, while 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) differed

from nonresponders (n=2), having stronger baseline expression of 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. Subsequent remissions and relapses in responders paralleled reduction

and re-expresssion respectively of T cell markers. A relative increased

expression of CD45RB and CD45RO on synovial CD3+ T cells was observed after

HDC + ASCT. No correlations were found between DAS and changes in B cells or

macrophages infiltration or synoviocytes.

CONCLUSIONS: HDC + ASCT results in profound but incomplete immunoablation of

both the memory and naive T cell compartment which is associated with long

lasting clinical responses in the majority of patients. Our findings provide

strong circumstantial evidence for a role of T cells in established

rheumatoid arthritis, and demonstrate a role for the synovium in

post-transplant T cell reconstitution.

PMID: 15829573

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_uids=1\

5829573 & dopt=Abstract

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