| Co-Investigator(Kenkyū-buntansha) |
AOZASA Katsuyuki Osaka University, Graduate School of Medicine, Professor, 医学系研究科, 教授 (30115985)
HONGYO Tadashi Osaka University, Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (90271569)
TOMITA Yasuhiko Osaka University, Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (60263266)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
Individuals affected by RA develop LPD at a frequency 2.0 to 5.5 times higher than that of the general population. Recently, a relationship between low-dose MTX medication and the development of LPD in RA patients was noticed. In this study, we analysed mechanism for development of LPD patients with rheumatoid arthritis (RA).
1)Clinicopathological features of rheumatoid arthritis (RA)-LPD
To characterize RA-LPD,48,28, and 150 cases of MTX-LPD, non-MTX-LPD, and sporadic LPD were evaluated. Majority of RA-LPD shows a similar clinicopathological characteristic irrespective of MTX medication except for spontaneous regression of LPD after withdrawal of MTX in MTX-LPD and shorter interval between the diagnosis of RA and LPD in MTX-than non-MTX-LPD. RA-LPD showed the younger onset age, female predominance, unfavorable prognosis, the higher frequencies of DLBCL and EBV positivity compared to sporadic LPD. (J Rheumatol, in revision)
2)Prognostic significance of CD40 expression was analyzed in B ce
… More
ll RA-LPD.
CD40, a member of tumor necrosis factor receptor superfamily, is expressed in synovial fluid B cells in rheumatoid arthritis (RA) and is postulated to contribute to RA progression. In this study, prognostic significance of CD40 expression was analyzed in B cell lymphoproliferative disorders (LPD) developing in RA. RA-LPD is characterized by the higher frequency of CD40 expression compared to sporadic LPD and CD40 positive cases which showed more favorable prognosis than those without CD40 expression. (J Cancer Res Clin Oncol,2005)
3)Gene mutations in LPD developing in AID.
Mutations of p53 tumor suppressor gene are associated with a poor prognosis in varying types of malignancies including sporadic B-cell lymphoma of aggressive type. p53 gene mutations were examined in 45 cases with LPD which developed in patients with prior history of AID. The frequency (46.6%) of p53 gene mutation in AID-LPD was much higher than that in the sporadic NHL (6-15%). Patients with p53 gene mutations showed less favorable prognosis than those without in not only B-cell but also T-cell NHL developing in AID. (in submission)
4)The first report of a Jananese patient with infliximab-associated LPD.
Infliximab is a chimeric monoclonal antibody that binds specifically and directly to human tumor necrosis factor (TNF-), a key player in the inflammatory response, and neutralizes its biologic activity. Infliximab therapy dramatically improved the complaints of RA patients, although an increase in the risk for developing lymphoproliferative disorders (LPD) under short-term use in the United States was indicated. We reported the first of a Japanese patient with infliximab-associated LPD to be described in the literature. (Int J Hematol,2005) Less
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