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  • P115 Belimumab treatment rapidly restores B cell homeostasis and reduces atypical T-bet+ B cell expansion in patients with systemic lupus erythematosus

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P115 Belimumab treatment rapidly restores B cell homeostasis and reduces atypical T-bet+ B cell expansion in patients with systemic lupus erythematosus
  1. Fulvia Ceccarelli1,
  2. Francesca La Gualana2,
  3. Gabriella Cusa2,
  4. Licia Picciariello1,
  5. Giulio Olivieri3,
  6. Begi Petriti2,
  7. Francesco Natalucci1,
  8. Maddalena Sciannamea2,
  9. Marcella Visentini2 and
  10. Fabrizio Conti1
  1. 1Lupus Clinic, Division of Rheumatology, Dept. of Internal Clinical Sciences, Anaesthesiologic and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
  2. 2Division of Clinical Immunology, Dept. of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
  3. 3Research Unit of Clinical Immunology and Vaccinology, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy; Chair of Pediatrics, Dept. of Systems Medicine, University of Rome Tor Vergata, Rome, Italy; PhD Program in Immunology, Molecular Medicine and Applied Biotechnology, University of Rome Tor Vergata, Rome, Italy

Abstract

Objective B cells alterations play a central role in Systemic lupus erythematosus (SLE) pathogenesis. Indeed, expansion of atypical CD21 low, Tbet+ or CD11c+ B cells has been observed in immune-related disorders, including SLE. BAFF inhibition impacts on peripheral B cells distribution and seems to promote negative selection of activated autoreactive B cells. Thus, we investigated the effect of BAFF inhibition through subcutaneous Belimumab (BLM) on peripheral B cell subpopulations, in particular T-bet+ B cells.

Methods We analysed SLE patients (ACR/EULAR 2019 criteria) candidate to BLM due to active disease. As control, we included age-matched healthy donors. Disease activity was assessed by SLEDAI-2 and SLE-DAS in all the established time-points [baseline (T0), after 1 (T1), 3 (T3), 6 (T6) and 12 (T12) months]. The achievement of remission was registered according to SLE-DAS values and DORIS definition. Flow cytometry was applied to analyse IgD+CD27+ Naïve, IgD+CD27+ Marginal Zone (MZ)-like, IgD-CD27+ switched memory (SW), and IgD-CD27- double negative (DN), atypical CD21 low CD11c + and T-bet + B cell subpopulations.

Results We enrolled 16 patients (M/F 3/13; median age 40.5 years, IQR 22.2; median disease duration 102 months, IQR 85.5; median SLEDAI-2k 6, IQR 6; median SLE-DAS 9.73, IQR 7.23) and 13 HD (M/F 2/11, median age 32 years, IQR 28.5). At baseline, SLE showed a significantly higher%T-bet+ in comparison with HD (p<0.0001; figure 1). During longitudinal observation, a significant reduction of SLEDA-2k and SLE-DAS was observed (p<0.0001 for all the time-points). We found a significantly decrease of T-bet+ at T1 (p=0.003), confirmed at subsequent time-points when considered the absolute number (T3 p=0.01; T6 p=0.001; T12 p=0.01). Similarly, we observed a significant reduction for%CD11c+ B cells (T1 p=0.02, T3 p=0.03, T6 p=0.04) and for the CD21low B cells (absolute count, T3 p=0.04, T6 p= 0.005) (figure 2). Furthermore,%T-bet+ was similar in patients and HD after 6 months of treatment; this data was confirmed only for patients reaching DORIS remission.

Abstract P115 Figure 1
Abstract P115 Figure 1

%CD19+T-bet+ in SLE patients and HD

Abstract P115 Figure 2
Abstract P115 Figure 2

Changes in T-bet+, CD11c+ and CD21low B cells during BLM treatment (*p<0.01)

Conclusions We confirm that atypical T-bet+ B cells are expanded in SLE. Furthermore, BLM treatment induces an early reduction of this B cell subset, in particular in patients achieving remission.

http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ .

https://doi.org/10.1136/lupus-2024-el.169

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