THU0038 Increase of circulating memory b cells after glucocorticoid-induced remission identifies patients at risk of igg4-related disease relapse
Authors: M. Lanzillotta, E. Della Torre, R. Milani, E. Bozzolo, E. Bozzalla Cassione, L. Rovati, M. Falconi, F. Ciceri, L. Dagna
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> IgG4-related disease (IgG4-RD) is relapsing-remitting systemic fibro-inflammatory condition characterised by elevated serum IgG4 concentration and by tumor-like lesions[.<sup>1</sup> Glucocorticoids represent the treatment of choice to induce IgG4-RD remission but relapses occur in almost 50% of patients at two years.<sup>2</sup> Several evidences suggest that B cells are central to the pathogenesis of IgG4-RD, the most significant being (i) the clinical improvement induced by B-cell depletion with rituximab, and (ii) the oligoclonal expansion of circulating plasmablasts in the vast majority of patients.<sup>3</sup> <h3>Objectives</h3> To describe alterations of B-lymphocyte subpopulations that might predict IgG4-RD relapse in patients treated with a first course of glucocorticoids according to international guidelines <h3>Methods</h3> Thirty patients with IgG4-RD were treated with glucocorticoids according to international consensus guidelines. Flow cytometry analysis of circulating CD19<sup>+</sup> and CD20<sup>+</sup> cells, naïve B cells, memory B cells, plasmablasts, and plasma cells was performed at baseline and every 6 months after the initiation of corticosteroid treatment. <h3>Results</h3> Patients with active untreated IgG4-RD showed reduced CD19<sup>+</sup> B cells, CD20<sup>+</sup> B cells, and naïve B cells compared to healthy controls (p&lt;0.05), but expanded plasmablasts and plasma cells (p&lt;0.01). Glucocorticoids treatment led to disease response in all patients. Clinical improvement was accompanied by a significant reduction of naïve B cells, circulating plasmablasts, and plasma cells, and by a significant increase of memory B cells compared to baseline (p&lt;0.01). Increase of circulating memory B cells was observed only in patients experiencing disease relapse and not in patients who maintained remission at two years of follow-up (HR:14.40, 95% CI 2.96–70.1, p&lt;0.01, figure 1 A-B). Relapse rates at 12 and 24 months were 25% and 100% with memory B cell increase at 6 months (figure 1C), respectively. No B-cell subpopulations were found to predict IgG4-RD relapse at disease onset. <h3>Conclusions</h3> The efficacy of glucocorticoids in IgG4-RD is associated with selective effects on different B-cell subpopulations. IgG4-RD relapse may be predicted by the increase of memory B-cells after glucocorticoid-induced remission <h3>References</h3> [1] Della-Torre E, Lanzillotta M, Doglioni C, Immunology of IgG4-related disease. Clin Exp Immunol. 2015;1881:191–206. [2] Khosroshahi A, Wallace ZS, Crowe JL, et al. International Consensus Guidance Statement on the Management and Treatment of IgG4-Related Disease. Arthritis Rheumatol2015;67:1688–99. [3] Wallace ZS, Mattoo H, Mahajan VS, et al. Predictors of disease relapse in IgG4-related disease following rituximab. Rheumatology (Oxford). 2016Jun;55(6):1000–8. <h3>Disclosure of Interest</h3> None declared