SAT0124 Decreased Titer of ANTI-CCP Antibodies and Rheumatoid Factor and Reduction of Post-Switch Memory B Cells After Abatacept Treatment for Rheumatoid Arthritis
Authors: M. Scarsi, G. Montico, S. Piantoni, L. Andreoli, F. Franceschini, A. Tincani, P. Airò
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> B cells play a central role in the pathophysiology of Rheumatoid Arthritis (RA). In particular, they can produce rheumatoid factor (RF) and other autoantibodies, including anti-cyclic citrullinated peptide (anti-CCP), whose presence is associated to a more severe disease. The capability of producing different classes of immunoglobulines (Ig), including autoantibodies is acquired, after antigen presentation in lymphoid tissue with the "help" of T lymphocytes, by a portion of B cells that can be identified phenotypically as <i>post-switch memory</i> cells (CD19+CD27+IgD-). Moreover, B cells can act as antigen-presenting cells, and activate T cells providing costimulation signals via CD80/CD86 to the CD28 receptor. Abatacept (ABA) is a fusion protein useful in the treatment of RA, which through its CTLA4 portion can bind to CD80 and CD86 on B cells, thereby inhibiting CD28 costimulation. Since CD28-mediated costimulation plays a crucial role in the acquisition of the T cell "helper" function, through the up-regulation of CD154 on T cell surface and the consequent engagement of CD40 (constitutively present on B cell membrane), it can be hypothesized that ABA may down-modulate the immune responses of B lymphocytes. <h3>Objectives</h3> To demonstrate whether the blockade of costimulation performed by ABA treatment may reduce the capability of B lymphocytes to differentiate into <i>post-switch memory</i> B cells and to produce anti-CCP and RF. <h3>Methods</h3> 30 RA patients (sex: 4 male, 26 female; age: 54 years (10<sup>th</sup>-90<sup>th</sup> percentile: 45-62)) treated for at least 6 consecutive months with ABA were enrolled in the study. B cell immune-phenotype was assessed by flow-cytometry. RF and anti-CCP Ab were measured by ELISA assays. The range of sensitivity for RF assay was 0.1-100.0 UI/mL. The clinical disease activity and the response to the treatment were evaluated respectively with the DAS28 (based on CRP) and the EULAR Criteria of Response to the treatment. <h3>Results</h3> At baseline 87% and 47% of patients resulted positive for anti-CCP IgG and IgA Ab respectively; 60%, 7%, 33% showed the presence of RF IgM, IgG and IgA. After 6 months of ABA treatment, 74% and 61% of patients achieved the EULAR good clinical response and the clinical remission, respectively. At this time, we observed a significant reduction of the titer of anti-CCP IgG: (from 273 (13-2354) to 184 (12-3044) IU/ml, p: 0.05), anti-CCP IgA (from 16 (2-549) to 13 (2-496) IU/ml, p:0.03), RF IgG (from 7.1 (0.8-33.0) to 2.8 (0-59.0) IU/ml, p:0.05), RF IgA (from 19.7 (1.4-&gt;100.0) to 12.4 (1.1-&gt;100.0) IU/ml, p:0.02), RF IgM (from &gt;100.0 UI/mL (2.4-&gt;100.0) to 31.0 (0.5-&gt;100.0) IU/ml, p:0.01), as well as of the proportion of <i>post-switch memory</i> B cells (from 9.1 (3.8-16.6) to 6.6 (3.5-9.1)% of B cells; p:0.03). No correlations was observed between the variation of these parameters and the modification of disease activity. <h3>Conclusions</h3> The costimulation blockade performed by ABA reduces serum levels of different classes of anti-CCP and RF, and limits the differentiation of B lymphocytes to the effector population of <i>post-switch memory</i> cells. <h3>Acknowledgements</h3> We acknowledge Bristol-Myers-Squibb for the support to our study <h3>Disclosure of Interest</h3> None Declared