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Deficient control of in vitro Epstein-Barr virus infection in patients with ankylosing spondylitis
Abstract:
Infectious Epstein-Barr (EB) virus obtained from the B95-8 marmoset cell line was used to infect mononuclear cells from healthy controls and patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS), and outgrowth of B cells into lymphoblastoid cell lines was assessed by visual microscopy and uptake of tritiated thymidine over a 28 day period. When undiluted virus was used lymphocytes from both patients with AS and RA and from normal controls outgrew into lymphoblastoid cell lines (LCLs) by day 28 of culture. At dilutions of 1/10, 1/20, and 1/40, however, the control cells showed regression of proliferation at approximately day 14 of culture, whereas the cells from patients with AS and RA continued to proliferate and outgrew into LCLs (transformation scores of cells from patients with AS compared with controls at day 28 p less than 0.05 in all cases; thymidine uptake at a 1/40 dilution at day 28, patients with AS compared with controls p less than 0.01). Hence these results suggest that there is a defect in the cellular response to EB virus induced B cell proliferation in patients with AS similar to that seen with cells from RA donors.
Insights
Patients with ankylosing spondylitis (AS) and rheumatoid arthritis (RA) show a cellular defect in Epstein-Barr virus (EBV) induced B cell proliferation, similar to healthy controls but with a delayed regression response.
Area of Science:
- Immunology
- Virology
- Rheumatology
Background:
- Epstein-Barr virus (EBV) is known to infect B cells, leading to lymphoblastoid cell line (LCL) formation.
- Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are chronic inflammatory conditions with potential links to viral infections.
Purpose of the Study:
- To investigate the cellular response to EBV infection in patients with RA and AS compared to healthy controls.
- To assess the proliferation and outgrowth of B cells into LCLs following EBV exposure.
Main Methods:
- Mononuclear cells from healthy controls, RA patients, and AS patients were infected with EBV from the B95-8 marmoset cell line.
- B cell outgrowth into LCLs was evaluated using microscopy and tritiated thymidine uptake over 28 days.
- Virus dilutions were used to assess dose-dependent cellular responses.
Main Results:
- At high virus concentrations, all groups formed LCLs.
- At lower virus dilutions (1/10, 1/20, 1/40), control cells regressed proliferation around day 14.
- Cells from AS and RA patients continued to proliferate and form LCLs at lower virus dilutions, indicating a sustained response (p<0.05 for AS vs. controls).
- Thymidine uptake was significantly higher in AS patients at a 1/40 dilution (p<0.01).
Conclusions:
- Patients with AS exhibit a defect in cellular response to EBV-induced B cell proliferation.
- This defect is similar to that observed in patients with RA.
- The findings suggest a potential role for EBV in the pathogenesis of AS and RA.