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


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


BACKGROUND
clinicaltrials.gov; https://clinicaltrials.gov/; NCT01008982.
Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Center, Rozzano, Milan.
Elena
E
Pontarini
Institute of Clinical Pathology, University Hospital of Udine.
Martina
M
Fabris
Department of Biological and Medical Sciences, University Hospital Rheumatology Clinic, Udine.
Luca
L
Quartuccio
Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Center, Rozzano, Milan, Department of Medical Biotechnologies and Translational Medicine, University of Milan, Milan and.
Monica
M
Cappeletti
Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Center, Rozzano, Milan, Department of Medical Biotechnologies and Translational Medicine, University of Milan, Milan and.
Francesca
F
Calcaterra
Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Center, Rozzano, Milan.
Alessandra
A
Roberto
Department of Medical and Biological Sciences, University of Udine, Udine, Italy.
Francesco
F
Curcio
Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Center, Rozzano, Milan, Department of Medical Biotechnologies and Translational Medicine, University of Milan, Milan and domenico.mavilio@humanitas.it.
Domenico
D
Mavilio
Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Center, Rozzano, Milan, Department of Medical Biotechnologies and Translational Medicine, University of Milan, Milan and.
Silvia
S
Della Bella
Department of Biological and Medical Sciences, University Hospital Rheumatology Clinic, Udine.
Salvatore
S
De Vita
D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology* / Q000627:therapeutic use*; D053264:B-Cell Activating Factor / Q000378:metabolism; D053265:B-Cell Activation Factor Receptor / Q000378:metabolism*; D016175:B-Lymphocyte Subsets / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D006706:Homeostasis; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D008875:Middle Aged; D012217:Rheumatoid Factor / Q000097:blood; D012859:Sjogren's Syndrome / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D016896:Treatment Outcome; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism; D015854:Up-Regulation
D061067:Antibodies, Monoclonal, Humanized; D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; C505719:TNFSF13B protein, human; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; C511911:belimumab; D012217:Rheumatoid Factor
B lymphocytes; BAFF-receptor; Sjogren’s syndrome; belimumab; transitional B lymphocytes