Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
EBV Infection In the Rheumatoid Synovium: Relationship with Ectopic Lymphoid Structures, In Situ Autoantobody Production and CD8 T Cell Activation.
Croia1, Cristina, Bombardieri1, Michele, Serafini2, Barbara, Coccia2, Eliana M., Severa2, Martina, Kelly1, Stephen, Aloisi1, Francesca
The ubiquitous y-herpesvirus Epstein-Barr virus (EBV) infects B cells and modifies their differentiation programme leading to B cell activation and immortalization. Increasing evidence supports a link between EBV and common B cell-related autoimmune diseases, i.e. multiple sclerosis (MS), myasthenia gravis (MG) and Sjogren's syndrome. Recent data demonstrated that ectopic B cell follicles in the brain of MS and the thymus of MG patients are preferential sites of EBV persistence and reactivation. Here we aimed to investigate the role of EBV in B cell dysregulation and autoimmunity in the RA synovium by analysing its relationship with ectopic lymphoid structures (ELS), B cell infiltration, in situ autoantibody production and cytotoxic immune response.
Forty RA synovial biopsies were characterized for the degree of B cell infiltration, the presence of ELS with germinal center-like structures (GC-LS) and the status of EBV latent and productive infection using immunohistochemistry (IHC), double immunofluorescence (IF), in situ hybridization (ISH) and real-time RT-PCR.
Using IHC and IF all 10 RA samples with GC-LS and 17 with high/medium B cell infiltration displayed evidence of EBV infection. Conversely, EBV+ cells were not detected in 13 RA samples with low/absent B cells. Latent EBV infection (LMP2A and EBER) was detected in a significant proportion of B cells, particularly within ELS. Using standard real-time RT-PCR, 40% of RA cases with high B cell infiltration were found LMP2A+, while after selective pre-amplification we observed that 100% of the RA cases were positive for LMP2A and LMP1 and 60% for EBER. In addition, numerous CD138+ plasma cells expressed the EBV early lytic antigen BFRF1 and were in close contact with CD8+ and/or granzyme B+ cells. Interestingly, a significant proportion of BFRF1+ plasma cells displayed reactivity against citrullinated fibrinogen. Finally, markers of productive viral infection (gp350/220, p160) were seldom found in RA samples with ELS.
Overall, these findings suggest that a dysregulated EBV infection likely exert an important role in the activation and differentiation of auto-reactive B cells within the RA synovium and might be partly responsible for the activation of a cytotoxic T cell response.
To cite this abstract, please use the following information:
Croia, Cristina, Bombardieri, Michele, Serafini, Barbara, Coccia, Eliana M., Severa, Martina, Kelly, Stephen, et al; EBV Infection In the Rheumatoid Synovium: Relationship with Ectopic Lymphoid Structures, In Situ Autoantobody Production and CD8 T Cell Activation. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :375