THU0395 Low Numbers of Blood and Salivary Natural Killer Cells are Associated with a Better Response to Belimumab in Primary Sjogren's Syndrome: Results of the Beliss Study
Authors: R. Seror, G. Nocturne, T. Lazure, H. Hendel-Chavez, F. Desmoulins, R. Belkhir, P. Ravaud, M. Benbijja, Y. Taoufik, X. Mariette
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> The BAFF (or BLyS) cytokine plays a key role in pathogenesis of primary Sjogren9s syndrome (pSS), thus testing belimumab (biological treatment inhibiting soluble BAFF/BLyS) in pSS patients, seems appealing. Clinical results of the BELISS study have been previously reported [1]. <h3>Objectives</h3> To address changes in blood lymphocyte sub-populations and labial salivary gland (LSG) inflammation after belimumab in patients with primary Sjögren9s syndrome (pSS) and identify predictors of response to treatment.To address changes in blood lymphocyte sub-populations and labial salivary gland (LSG) inflammation after belimumab in patients with primary Sjögren9s syndrome (pSS) and identify predictors of response to treatment. <h3>Methods</h3> Sequential blood lymphocyte subsets and LSG biopsies were analysed between week 0 (W0) and W28 in 15 pSS patients (all females, median age =44 [36.5-63.5] years, median disease duration=1 [0.5-6.5] years) treated with belimumab. Systemic response to treatment was defined as a decrease of the ESSDAI ≥3 points at W28. <h3>Results</h3> After belimumab, we observed a decrease in blood B lymphocytes primarily involving CD27-IgD+ naïve B-cells (151 [24-186] at W0 vs 10 [6-40] at W28, p=0.008, n=9). No significant change in the total lymphocyte, total T-cell, CD4 or CD8 T-cell counts was observed. By contrast, there was a significant increase in the number of NK cells (p=0.032) Regarding histological pattern, lymphocytic sialadenitis (focus score &gt;1) present in 12 (80.0%) patients before belimumab, became negative in 5 after treatment (p=0.03). The median LSG B-cell /T-cell ratio decreased from 0.58 [0.5-0.67] to 0.50 [0.5-0.5] (p=0.06). BAFF staining was detected in 11/14 (78.6%) patients, before, compared to 7/14 (50.0%) after belimumab (p=0.10). The median percentage of BAFF positive cells in foci significantly decreased from 27.5% [10-40] to 5% [0-20], after belimumab (p=0.03). Systemic response was obtained in 6 (40%) patients. The only predictor of response was the presence of a low number of NK cells both in blood (8.5% [7-10] vs. 11% [9-21], p=0.04) and in LSG (20.6/mm<sup>3</sup> [20.0-21.4] vs 30.0/mm<sup>3</sup> [25.0-100.0], p=0.003). Serum BAFF levels did not influence response to treatment. <h3>Conclusions</h3> Low blood and salivary NK cells numbers are associated with a better response to belimumab. This suggests that 2 distinct subsets of pSS may exist: one with predominant type-I INF/BAFF/B-cell axis, good responders to belimumab, and one with predominant type-II IFN/NK-cell axis, non-responders. <h3>References</h3> Mariette X, Seror R, Quartuccio L, Baron G, Salvin S, Fabris M, et al. Efficacy and safety of belimumab in primary Sjogren9s syndrome: results of the BELISS open-label phase II study. Annals of the rheumatic diseases. 2013. <h3>Disclosure of Interest</h3> None declared