2002 Fiscal Year Final Research Report Summary
Analysis of RP105 in association with the B cell activation in autoimmune diseases
| Project/Area Number |
13670459
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
内科学一般
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| Research Institution | Saga Medical School |
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Principal Investigator |
NAGASAWA Kohei Saga Medical School, Internal Medicine, Professor, 医学部, 教授 (00108721)
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| Co-Investigator(Kenkyū-buntansha) |
TADA Yoshifumi Saga Medical School, Internal Medicine, Instructor, 医学部, 講師 (70284627)
KOARADA Syuichi Saga Medical School, Internal Medicine, Instructor, 医学部, 助手 (50304887)
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| Project Period (FY) |
2001 – 2002
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| Keywords | B cell / RP105 / Autoimmune disease / SLE / Sjogren.s Syndrome / Immunoglobulin / Anti-DNA antibody / Immunohistochemical staining |
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| Research Abstract |
RP105, a novel molecule expressed on B cells, has been described to be associated with B cell proliferation or apoptosis in mice. We have already demonstrated that significant percent of B cells in patients with several autoimmune diseases lack RP105 molecules although virtually all peripheral B cells in normal subjects express them on their surface. We have also suggested that those RP105-negative B cells are highly activated and may be associated with the pathophysiology of those autoimmune diseases. In this study we investigated whether RP105-negative B cells from patients with systemic lupus erythematosus (SLE) could produce immunoglobulins (Ig) and anti-DNA antibodies, critically important autoantibodies in SLE, in vitro. We found that RP105- positive B cells produced neither Ig nor anti-DNA antibodies even with various - stimulations. On the other hand, RP105-negative B cells from all the SLE patients produced significant amount of Ig without any stimulation and anti-DNA antibodi
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es when incubated with T cells. Moreover, these production was augmented with the addition of IL-6.
RP105-negative B cells in the peripheral blood from patients with Sjogren's syndrome, another important disease characteristic of B cell activation, were also found to be increased and we analyzed the expression of RP105 on B cells infiltrating salivary glands by immunohistochemical staining. The results showed that large proportion of B ills that infiltrated and proliferated in the salivary glands were RP105-negative. It was also found that the degree of infiltrating RP105-negative B cells tended to correlate with the serum levels of Ig, indicating that those cells may be responsible for the production of Ig and possibly autoantibodies in Sjogren's syndrome as well.
Taken together, RP105-negative B cells may play an important role in the pathogenesis of certain autoimmune diseases such as SLE and Sjogren's syndrome. We are planning to develop a treatment of those diseases taking advantage of the character of RP105-negative B cells. Less
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