Treatment with belimumab restores B cell subsets and their expression of B cell activating factor receptor in patients with primary Sjogren's syndrome

Elena Pontarini, Martina Fabris, Luca Quartuccio, Monica Cappeletti, Francesca Calcaterra, Alessandra Roberto, Francesco Curcio, Domenico Mavilio, Silvia Della Bella, Salvatore De Vita

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

OBJECTIVE: The aim of this study was to investigate the biological effects of belimumab on B cells in the first phase II open-label trial with belimumab in patients with primary SS (pSS) (BELISS).

METHODS: Peripheral blood B cell subsets and their B cell activating factor-receptor (BAFF-R) expression were analysed by multicolour flow cytometry in 10 pSS patients either before or after 24 and 52 weeks of therapy with belimumab. Serum BAFF levels were analysed by ELISA.

RESULTS: At baseline, pSS patients showed a significant increase in circulating B cells compared with healthy donors matched for age and sex, with a predominant expansion of transitional and naive B cell subsets. pSS patients also showed higher serum BAFF levels and lower B cell BAFF-R expression. Therapy with belimumab in pSS patients induced a significant reduction in transitional and naive B cell subsets to levels similar to those observed in healthy donors. Furthermore, belimumab normalized BAFF-R expression in all B subsets comprised within the memory compartment. The restoration of B cell frequency and subset composition in response to belimumab was also associated with a decrease in serum levels of Ig, RF, ANAs, and with an increase in the C4 complement fraction. All of these belimumab-mediated effects were observed after 24 weeks of therapy and maintained until the end of the therapeutic protocol.

CONCLUSION: Taken together, our findings show that targeting BAFF with belimumab is successful in normalizing B cell frequency, phenotype and functions in pSS.

TRIAL REGISTRATION: clinicaltrials.gov; https://clinicaltrials.gov/; NCT01008982.

Original languageEnglish
Pages (from-to)1429-1434
Number of pages6
JournalRheumatology
Volume54
Issue number8
DOIs
Publication statusPublished - Aug 1 2015

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Interleukin-4 Receptors
B-Lymphocyte Subsets
Sjogren's Syndrome
B-Lymphocytes
B-Lymphoid Precursor Cells
Therapeutics
Serum
Tissue Donors
Complement C4
belimumab
Blood Cells
Flow Cytometry
Enzyme-Linked Immunosorbent Assay
Phenotype

Keywords

  • B lymphocytes
  • BAFF-receptor
  • belimumab
  • Sjogren’s syndrome
  • transitional B lymphocytes

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Treatment with belimumab restores B cell subsets and their expression of B cell activating factor receptor in patients with primary Sjogren's syndrome. / Pontarini, Elena; Fabris, Martina; Quartuccio, Luca; Cappeletti, Monica; Calcaterra, Francesca; Roberto, Alessandra; Curcio, Francesco; Mavilio, Domenico; Della Bella, Silvia; De Vita, Salvatore.

In: Rheumatology, Vol. 54, No. 8, 01.08.2015, p. 1429-1434.

Research output: Contribution to journalArticle

Pontarini, Elena ; Fabris, Martina ; Quartuccio, Luca ; Cappeletti, Monica ; Calcaterra, Francesca ; Roberto, Alessandra ; Curcio, Francesco ; Mavilio, Domenico ; Della Bella, Silvia ; De Vita, Salvatore. / Treatment with belimumab restores B cell subsets and their expression of B cell activating factor receptor in patients with primary Sjogren's syndrome. In: Rheumatology. 2015 ; Vol. 54, No. 8. pp. 1429-1434.
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T1 - Treatment with belimumab restores B cell subsets and their expression of B cell activating factor receptor in patients with primary Sjogren's syndrome

AU - Pontarini, Elena

AU - Fabris, Martina

AU - Quartuccio, Luca

AU - Cappeletti, Monica

AU - Calcaterra, Francesca

AU - Roberto, Alessandra

AU - Curcio, Francesco

AU - Mavilio, Domenico

AU - Della Bella, Silvia

AU - De Vita, Salvatore

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Y1 - 2015/8/1

N2 - OBJECTIVE: The aim of this study was to investigate the biological effects of belimumab on B cells in the first phase II open-label trial with belimumab in patients with primary SS (pSS) (BELISS).METHODS: Peripheral blood B cell subsets and their B cell activating factor-receptor (BAFF-R) expression were analysed by multicolour flow cytometry in 10 pSS patients either before or after 24 and 52 weeks of therapy with belimumab. Serum BAFF levels were analysed by ELISA.RESULTS: At baseline, pSS patients showed a significant increase in circulating B cells compared with healthy donors matched for age and sex, with a predominant expansion of transitional and naive B cell subsets. pSS patients also showed higher serum BAFF levels and lower B cell BAFF-R expression. Therapy with belimumab in pSS patients induced a significant reduction in transitional and naive B cell subsets to levels similar to those observed in healthy donors. Furthermore, belimumab normalized BAFF-R expression in all B subsets comprised within the memory compartment. The restoration of B cell frequency and subset composition in response to belimumab was also associated with a decrease in serum levels of Ig, RF, ANAs, and with an increase in the C4 complement fraction. All of these belimumab-mediated effects were observed after 24 weeks of therapy and maintained until the end of the therapeutic protocol.CONCLUSION: Taken together, our findings show that targeting BAFF with belimumab is successful in normalizing B cell frequency, phenotype and functions in pSS.TRIAL REGISTRATION: clinicaltrials.gov; https://clinicaltrials.gov/; NCT01008982.

AB - OBJECTIVE: The aim of this study was to investigate the biological effects of belimumab on B cells in the first phase II open-label trial with belimumab in patients with primary SS (pSS) (BELISS).METHODS: Peripheral blood B cell subsets and their B cell activating factor-receptor (BAFF-R) expression were analysed by multicolour flow cytometry in 10 pSS patients either before or after 24 and 52 weeks of therapy with belimumab. Serum BAFF levels were analysed by ELISA.RESULTS: At baseline, pSS patients showed a significant increase in circulating B cells compared with healthy donors matched for age and sex, with a predominant expansion of transitional and naive B cell subsets. pSS patients also showed higher serum BAFF levels and lower B cell BAFF-R expression. Therapy with belimumab in pSS patients induced a significant reduction in transitional and naive B cell subsets to levels similar to those observed in healthy donors. Furthermore, belimumab normalized BAFF-R expression in all B subsets comprised within the memory compartment. The restoration of B cell frequency and subset composition in response to belimumab was also associated with a decrease in serum levels of Ig, RF, ANAs, and with an increase in the C4 complement fraction. All of these belimumab-mediated effects were observed after 24 weeks of therapy and maintained until the end of the therapeutic protocol.CONCLUSION: Taken together, our findings show that targeting BAFF with belimumab is successful in normalizing B cell frequency, phenotype and functions in pSS.TRIAL REGISTRATION: clinicaltrials.gov; https://clinicaltrials.gov/; NCT01008982.

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