       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).

