Session Type: Abstract Submissions (ACR)
Autoimmune disease affects more than 23 million Americans. Systemic Lupus Erythematosus (SLE) and Rheumatoid Arthritis (RA) are chronic, systemic B-cell mediated autoimmune diseases. During normal B cell development, autoreactive B cells are eliminated by negative selection processes that include receptor editing, anergy, or apoptosis. The increased numbers of autoreactive B cells in SLE and RA suggests that these patients have defects in negative selection that occurs during the immature stages of B cell development. The tumor necrosis factor (TNF) family members APRIL and BAFF have been shown to promote the survival of immature and naive B cells in mouse models of autoimmune disease. Elevated levels of BAFF and APRIL may contribute to the breakdown of negative selection mechanisms. Serum levels of APRIL and BAFF are elevated in patients with SLE and RA and surface forms of these proteins have been detected on normal and/or malignant B lineage cells. Using flow cytometry we found surface forms of APRIL and BAFF on peripheral blood B cells from SLE and RA patients. The aim of this study is to compare surface expression of APRIL and BAFF and their receptors on B cells from SLE and RA patients to normal B cells and to elucidate their roles in B cell-mediated autoimmunity.
Methods: Venous peripheral blood (PB) samples were collected from normal, RA, and SLE patients through an IRB-approved protocol. SLE and RA diagnosis was confirmed using American College of Rheumatology (ACR) criteria. Peripheral blood mononuclear cells (PBMCs) were separated from whole blood by red blood cell lysis. Human adult peripheral blood samples were stained for seven-color flow cytometry to assess co-expression of CD24, CD21, IgD, IgM, CD38, CD27, CD256 (APRIL), CD257 (BAFF), CD267 (TACI), and BR3 (BAFF-R). Stained cells were analyzed using a MACSQuant Analyzer (Miltenyi) and FlowJo analysis software (Tree Star). Mean fluorescence intensities (MFI) for surface APRIL and other markers on B cells from RA and SLE patient samples were compared to normal controls by one-tailed, unpaired t-test, p<0.05.
Results: Peripheral blood B cells obtained from normal (n=11), SLE (n=13), and RA (n=12) were characterized by flow cytometry. The MFI of APRIL, BAFF, BAFFR and TACI on CD19+IgM+ B cells of RA and SLE patients were compared to normal PB. Surface APRIL expression was significantly higher on B cells from RA (p=0.0083) and SLE (p=0.0146) patients as compared to normal donors. The receptor, TACI, which binds both APRIL and BAFF was also increased on B cells from RA (p=0.0114) and SLE (p=0.0146) patients.
Conclusion: Expression of surface APRIL and the TACI receptor are significantly higher on B cells from RA and SLE patients as compared to normal B cells. These results show that in SLE and in RA the patient’s B cells themselves serve as a reservoir of surface APRIL that provides a potential source of stimulation for the TACI receptors that are also upregulated on these cells. These data implicate surface APRIL and TACI in B-cell mediated autoimmune disease. Ongoing studies are focused on establishing the relationship between the level of surface APRIL expression and disease activity.
A. J. Weldon,
S. K. Nazeri,
A. D. Parra,
K. K. Colburn,
K. J. Payne,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/expression-of-surface-april-and-its-receptor-taci-is-upregulated-on-b-cells-from-systemic-lupus-erythematosus-and-rheumatoid-arthritis-patients/