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Correlation between Circulating Plasmablasts and Disease Activity in Patients with ACPA+ Rheumatoid Arthritis
S138 peritonitis (SBP). The exact mechanisms that cause SBP are unknown. Patients with HC usually present a variety of immunologic complications such as: deficient bactericide action in serum, opsonin and complement defects, and neutrophil dysfunction. Paneth cells act as immune cells eliminating microorganisms through to release antimicrobial peptides, whose activity consists in the creation of pores on the pathogens’ membranes. The aim of this study was to evaluate the implications of 5α-defensin in the development of SBP in patients with hepatic cirrhosis. Materials and methods: Terminal ileum biopsies from 18 patients were analyzed to determine the expression of 5 α-defensin by immunohistochemistry. Results: Out of the 18 patients included in the study, 5 had only HC, 10 had HC and ascites without SBP, and 13 had HC and ascites with SBP. The expression of 5 α-defensin was found as follows: 10±2.2 (positive cell %) in patients with HC, 32±6.9 in patients with HC and ascites without SBP, and 70±6.6 in patients with HC and ascites with SBP. Conclusions: Data from our study indicates that 5 α-defensin produced by Paneth cells from HC patients who develop SBP, respond to infectious stimuli producing great amounts of this defensin. However, they seem unable to eliminate the pathogens. doi:10.1016/j.clim.2010.03.417
S.97. Correlation between Circulating Plasmablasts and Disease Activity in Patients with ACPA+ Rheumatoid Arthritis Yann Chong Tan, Jeremy Sokolove, William Robinson. Stanford University School of Medicine, Stanford, CA Rheumatoid arthritis (RA) is characterized by the production of autoantibodies and recent clinical trials using B cell depletion support the role of humoral immunity in RA. Extrafollicular germinal center-like structures are found in RA synovial tissue and suggest ongoing antigen recognition-dependent B cell activation. We sought to evaluate the correlation of circulating plasmablasts with disease activity in RA. To do so, we performed a pilot study of RA patients with varying degrees of disease activity. Using FACS analysis, we found a trend toward an increased frequency of CD19 +CD20-CD27+CD38+ plasmablasts in anti-citrullinated protein antibody (ACPA)+ RA patients demonstrating moderate or high disease activity as compared to those with quiescent ACPA+ RA. ACPA- RA, psoriatic arthritis, gout and osteoarthritis exhibited lower frequencies of plasmablasts, regardless of disease activity. These findings suggest that B cell activation may contribute to disease activity in ACPA+ RA patients. We hypothesize that disruption of the dynamic generation of synovial antigen-specific plasmablasts from CD20+ naïve or memory B cells could provide a mechanistic explanation of the effectiveness of B cell depletion therapy, despite only partial decline in ACPA-producing plasma cells. The findings identified above are being validated in a larger cohort of RA patients. Additional studies are ongoing to investigate the antigenic specificity of the identified plasmablasts, the dynamics of ACPA fine specificity after B cell depletion therapy, and to characterize the mechanisms of extrafollicular antigen-driven B cell activation. doi:10.1016/j.clim.2010.03.418
Abstracts
S.98. Mast Cells Contribute to Synovial Inflammation in Non-psoriatic and Psoriatic Spondyloarthritis Nataliya Yeremenko 1, Troy Noordenbos 1, Tineke Cantaert 1, Marleen van de Sande 1, Paul-Peter Tak 1, Juan D Cañete 2, Dominique Baeten 1. 1Academic Medical Center-Amsterdam, Amsterdam, Netherlands; 2Hospital Clinic de Barcelona and IDIBAPS, Barcelona, Spain We recently observed a striking synovial infiltration with cells positive for C-kit, a marker for mast cells and hematopoietic stem cells, in psoriatic arthritis (PsA). As mast cells have potent inflammatory functions, including the production of TNF, we performed a systematic analysis of C-kit+ cells in different forms of chronic inflammatory arthritis. C-kit+ mononuclear cells were found in the synovial sublining in all disease groups but were significantly increased in SpA and PsA versus RA despite similar levels of global inflammation as reflected by CD3, CD20, and CD68 staining. Double staining confirmed that C-kit+ cells were mast cells. SF levels of SCF, IL3, and IL-33, factors involved in chemotaxis and differentiation of mast cells, as well as sST2, the soluble decoy receptor for IL33, were similar in all groups. Most mast cells in SpA synovium were degranulated as indicated by double staining and by SF analysis for mast cell products. Interestingly, the synovial infiltration with C-kit positive cells in SpA persisted despite successful treatment with TNF blockers. However, C-kit inhibition in vitro strongly reduced the production (mRNA by qPCR) and secretion (protein by ELISA) of IL-6 and IL-8 by synovial biopsies, suggesting that mast cells contribute to the ongoing inflammatory process. There is an increased synovial infiltration with and degranulation of C-kit+ mast cells in SpA and PsA. Inhibition of C-kit in vitro leads to reduction of proinflammatory cytokine production by synovial biopsies. These data suggest a role for mast cells in driving and/or sustaining the synovial inflammation in SpA. doi:10.1016/j.clim.2010.03.419
S.99. Serum Mannose Binding Lectin Levels in Different Clinical Forms of Hepatitis B Infection Yesim Alpay, Ergin Ayaslioglu, Fahri Yakaryilmaz, Ucler Kisa. Medical School of Kirikkale University, Kirikkale, Turkey Hepatitis B virus (HBV) infection can result in numerous different clinical outcomes. Complex interaction of viral, genetic and enviromental factors seems to be responsible for both susceptibility to HBV persistence and the course of infection. Mannose binding lectin (MBL) is a pattern recognition molecule of the innate immune system that binds to sugars on the surface of invading micro-organisms. Previous studies have reported an association between MBL deficiency and chronic HBV infection in adults. The aim of the present study was to investigate the role of MBL in HBV infection. For this purpose, 77 consecutive patients with HBVinfection (23 chronic HBV infections, 54 inactive HBsAg carriers) and 70 control subjects were enrolled into a prospective study. We measured serum concentrations of MBL by using enzyme linked immunosorbent assay. MBL levels of chronic HBV infection, inactive HBsAg carrier and control groups were found as
S.97. Correlation between Circulating Plasmablasts and Disease Activity in Patients with ACPA+ Rheumatoid Arthritis Yann Chong Tan, Jeremy Sokolove, William Robinson. Stanford University School of Medicine, Stanford, CA Rheumatoid arthritis (RA) is characterized by the production of autoantibodies and recent clinical trials using B cell depletion support the role of humoral immunity in RA. Extrafollicular germinal center-like structures are found in RA synovial tissue and suggest ongoing antigen recognition-dependent B cell activation. We sought to evaluate the correlation of circulating plasmablasts with disease activity in RA. To do so, we performed a pilot study of RA patients with varying degrees of disease activity. Using FACS analysis, we found a trend toward an increased frequency of CD19 +CD20-CD27+CD38+ plasmablasts in anti-citrullinated protein antibody (ACPA)+ RA patients demonstrating moderate or high disease activity as compared to those with quiescent ACPA+ RA. ACPA- RA, psoriatic arthritis, gout and osteoarthritis exhibited lower frequencies of plasmablasts, regardless of disease activity. These findings suggest that B cell activation may contribute to disease activity in ACPA+ RA patients. We hypothesize that disruption of the dynamic generation of synovial antigen-specific plasmablasts from CD20+ naïve or memory B cells could provide a mechanistic explanation of the effectiveness of B cell depletion therapy, despite only partial decline in ACPA-producing plasma cells. The findings identified above are being validated in a larger cohort of RA patients. Additional studies are ongoing to investigate the antigenic specificity of the identified plasmablasts, the dynamics of ACPA fine specificity after B cell depletion therapy, and to characterize the mechanisms of extrafollicular antigen-driven B cell activation. doi:10.1016/j.clim.2010.03.418
Abstracts
S.98. Mast Cells Contribute to Synovial Inflammation in Non-psoriatic and Psoriatic Spondyloarthritis Nataliya Yeremenko 1, Troy Noordenbos 1, Tineke Cantaert 1, Marleen van de Sande 1, Paul-Peter Tak 1, Juan D Cañete 2, Dominique Baeten 1. 1Academic Medical Center-Amsterdam, Amsterdam, Netherlands; 2Hospital Clinic de Barcelona and IDIBAPS, Barcelona, Spain We recently observed a striking synovial infiltration with cells positive for C-kit, a marker for mast cells and hematopoietic stem cells, in psoriatic arthritis (PsA). As mast cells have potent inflammatory functions, including the production of TNF, we performed a systematic analysis of C-kit+ cells in different forms of chronic inflammatory arthritis. C-kit+ mononuclear cells were found in the synovial sublining in all disease groups but were significantly increased in SpA and PsA versus RA despite similar levels of global inflammation as reflected by CD3, CD20, and CD68 staining. Double staining confirmed that C-kit+ cells were mast cells. SF levels of SCF, IL3, and IL-33, factors involved in chemotaxis and differentiation of mast cells, as well as sST2, the soluble decoy receptor for IL33, were similar in all groups. Most mast cells in SpA synovium were degranulated as indicated by double staining and by SF analysis for mast cell products. Interestingly, the synovial infiltration with C-kit positive cells in SpA persisted despite successful treatment with TNF blockers. However, C-kit inhibition in vitro strongly reduced the production (mRNA by qPCR) and secretion (protein by ELISA) of IL-6 and IL-8 by synovial biopsies, suggesting that mast cells contribute to the ongoing inflammatory process. There is an increased synovial infiltration with and degranulation of C-kit+ mast cells in SpA and PsA. Inhibition of C-kit in vitro leads to reduction of proinflammatory cytokine production by synovial biopsies. These data suggest a role for mast cells in driving and/or sustaining the synovial inflammation in SpA. doi:10.1016/j.clim.2010.03.419
S.99. Serum Mannose Binding Lectin Levels in Different Clinical Forms of Hepatitis B Infection Yesim Alpay, Ergin Ayaslioglu, Fahri Yakaryilmaz, Ucler Kisa. Medical School of Kirikkale University, Kirikkale, Turkey Hepatitis B virus (HBV) infection can result in numerous different clinical outcomes. Complex interaction of viral, genetic and enviromental factors seems to be responsible for both susceptibility to HBV persistence and the course of infection. Mannose binding lectin (MBL) is a pattern recognition molecule of the innate immune system that binds to sugars on the surface of invading micro-organisms. Previous studies have reported an association between MBL deficiency and chronic HBV infection in adults. The aim of the present study was to investigate the role of MBL in HBV infection. For this purpose, 77 consecutive patients with HBVinfection (23 chronic HBV infections, 54 inactive HBsAg carriers) and 70 control subjects were enrolled into a prospective study. We measured serum concentrations of MBL by using enzyme linked immunosorbent assay. MBL levels of chronic HBV infection, inactive HBsAg carrier and control groups were found as