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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
  1. R. Seror1,
  2. G. Nocturne1,
  3. T. Lazure1,
  4. H. Hendel-Chavez1,
  5. F. Desmoulins1,
  6. R. Belkhir1,
  7. P. Ravaud2,
  8. M. Benbijja1,
  9. Y. Taoufik1,
  10. X. Mariette1
  1. 1Hopitaux Universitaires Paris Sud, Le Kremlin-Bicetre
  2. 2Hopital Hotel Dieu, Paris, France

Abstract

Background The BAFF (or BLyS) cytokine plays a key role in pathogenesis of primary Sjogren's 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].

Objectives To address changes in blood lymphocyte sub-populations and labial salivary gland (LSG) inflammation after belimumab in patients with primary Sjögren's 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 Sjögren's syndrome (pSS) and identify predictors of response to treatment.

Methods 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.

Results 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 >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/mm3 [20.0-21.4] vs 30.0/mm3 [25.0-100.0], p=0.003). Serum BAFF levels did not influence response to treatment.

Conclusions 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.

References

  1. Mariette X, Seror R, Quartuccio L, Baron G, Salvin S, Fabris M, et al. Efficacy and safety of belimumab in primary Sjogren's syndrome: results of the BELISS open-label phase II study. Annals of the rheumatic diseases. 2013.

Disclosure of Interest None declared

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