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1996-01-30
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Document 0002
DOCN M9610002
TI Reduction of synovial inflammation after anti-CD4 monoclonal antibody
treatment in early rheumatoid arthritis.
DT 9601
AU Tak PP; van der Lubbe PA; Cauli A; Daha MR; Smeets TJ; Kluin PM;
Meinders AE; Yanni G; Panayi GS; Breedveld FC; University Hospital
Leiden, The Netherlands.
SO Arthritis Rheum. 1995 Oct;38(10):1457-65. Unique Identifier : AIDSLINE
MED/96017443
AB OBJECTIVE. To study the effect of chimeric anti-CD4 monoclonal antibody
(MAb) therapy on synovial inflammation, in order to interpret the
clinical experience with anti-CD4 treatment. METHODS. The
immunohistologic features of synovial biopsy specimens before and 4
weeks after anti-CD4 MAb (cM-T412) therapy were studied in patients with
rheumatoid arthritis. The patients received intravenous doses of either
placebo (n = 1) or 10 mg (n = 4), 25 mg (n = 2), or 50 mg (n = 1) of
cM-T412 daily for 5 consecutive days. RESULTS. Although the patients did
not experience clinical improvement, significant decreases in the number
of circulating CD4+ cells, the degree of synovial inflammatory
infiltration, and the mean scores for expression of adhesion molecules
were found in the 7 patients 4 weeks after receiving cM-T412. The scores
for infiltration with CD4+ and other inflammatory cells were
particularly reduced following treatment with either 25 mg or 50 mg
cM-T412. Cytokines, such as interleukin-1 beta and tumor necrosis factor
alpha, could still be detected in the synovial tissue after treatment.
CONCLUSION. The decline in the numbers of inflammatory cells and
adhesion molecules in synovial tissue after CD4+ cell depletion supports
the view that CD4+ T cells orchestrate local cellular infiltration. The
lack of clinical effect of anti-CD4 therapy might be explained by an
insufficient decrease in the number of synovial CD4+ cells and by the
persistence of cytokines. Determination of whether more adequate dosing
would lead to a clinical improvement must await further study.
DE Adult Aged Antibodies, Monoclonal/*THERAPEUTIC USE Antigens,
CD4/*IMMUNOLOGY Arthritis,
Rheumatoid/COMPLICATIONS/IMMUNOLOGY/PATHOLOGY/*THERAPY
Cytokines/ANALYSIS CD4 Lymphocyte Count Double-Blind Method Female
Human Male Middle Age Synovial Membrane/IMMUNOLOGY/PATHOLOGY
Synovitis/IMMUNOLOGY/PATHOLOGY/*PREVENTION & CONTROL Time Factors
CLINICAL TRIAL JOURNAL ARTICLE RANDOMIZED CONTROLLED TRIAL
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).