KIMURA Tomoatu Osaka University Medical School, Orthopedic Surgery, Assistant Professor, 医学部, 講師 (80167379)
ONO Keiro Osaka University Medical School, Orthopedic Surgery, Professor, 医学部, 教授 (70028330)
|Budget Amount *help
¥11,000,000 (Direct Cost : ¥11,000,000)
Fiscal Year 1991 : ¥900,000 (Direct Cost : ¥900,000)
Fiscal Year 1990 : ¥2,200,000 (Direct Cost : ¥2,200,000)
Fiscal Year 1989 : ¥7,900,000 (Direct Cost : ¥7,900,000)
Di-and trifticosyl N-acetyllactosamine structures have been found as oncofetal markers defined by monoclonal antibody FH4 (J Biol Chem, 1984). Recently these membrance structures were identified in the abnormal myeloid cells found in the involved epiphyseal bone marrow of severe RA patients (Ochi et al, 1988).
Recently, sialyl Lewis X was found to mediate the cell adhesion by ELAM-1 (Phillips et al, 1990). Thus, carbohydrate membrance structure was found to be important in relation to the patholgy of RA.
We have tried the sensitization therapy with some carbohydrate structures to normalize the pathologic lesions in RA patients. As antigens, we used mono-, and di-fticosylated type 2 chain (mono-LeX, and di-Lex ; 500ng for each injection) bolind to liposome, and a high molecular weight glycoprotein derived from KATOIll cells (TCA ; provided by JIMBO ; 50 or 2 ng for one injection). One sensitization schedule was intradermal injection at day 1 and 2 with following 12 days interval (one cour
The first study was the investigation of the effect of i. d. injection of carbohydrate materials on the myeloid cell population present in epiphyseal bone marrow adjacent to a joint with active severe RA. Among RA patients with those abnormal cells, epiphyseal bone marrow cells were re-examined after 2 or more course terms of i. d. injections (1 to 4 months ; mean 2.5 months). The ratio of abnormal myeloid cells to whole mononuclear cells was assessed by facs. The mean ratios (N=10) before and after the i. d. injections of di-LeX were 8.32 (SD : 2.54) and 2.04 (SD : 1.81), respectively. The abnormal myeloid cells were, even if temporality, eliminated from the involved epipyseal bone marrow.
The second study was open trials to assessed the effects of materials and dosis. As the effective cases, not only clinical improvements bu't also the normalization of one or more laboratory data (IgM-RF, IgG-RF, CRP, ESR) were needed after 3 or 6 months of treatments. As antigens, di-LeX and TCA were effective both at 3 and 6 months' treatments. However, mono-Le^X showed no significant effect so far. Among the 105 trials with carbohydrate antigens, 15cases (14%) showed adverse effects ; skin eruption (11 cases), stomatitis aphtosa (2 cases) and hairloss (2 cases).
The Incidences of effective cases (among 132 trials) were as below.
Antigens Used Placebo di-LeX mono-LeX 2nd-TCA 50ng-TCA
After 3M 6/27(22%) 20/29(69%) 0/5(0%) 12/24(50%) 29/47(62%)
After 6M 6/25(24%) 17/27(63%) N. D. 14/22(64%) 31/43(72%)
Carbohydrate structures COLild be good materials in treating RA patients. Although the mecanisms are still obscure. Less