RESEARCH - B cell depletion therapy in SLE: relationships among serum B lymphocyte stimulator levels, autoantibody profile and clinical response

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Published Online First: 25 October 2007. doi:10.1136/ard.2007.079418

ls of the Rheumatic Diseases 2008;67:1011-1016

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EXTENDED REPORTS

B cell depletion therapy in systemic lupus erythaematosus:

relationships among serum B lymphocyte stimulator levels, autoantibody

profile and clinical response

G Cambridge 1, D A Isenberg 1, J C W 1, M J Leandro 1, T-S

Migone 2, M Teodorescu 3, W Stohl 4

1 Centre for Rheumatology Research, Department of Medicine, University

College London, London, UK

2 Human Genome Sciences, Inc., Rockville, land, USA

3 University of Illinois, College of Medicine, Chicago, Illinois, USA

4 Division of Rheumatology, Department of Medicine, University of

Southern California Keck School of Medicine, Los Angeles, California,

USA

Objective: To assess the relationships between serum B lymphocyte

stimulator (BLyS) levels, autoantibody profile and clinical response

in patients with systemic lupus erythaematosus (SLE) following

rituximab-based B cell depletion therapy (BCDT).

Methods: A total of 25 patients with active refractory SLE were

followed for 1 year following BCDT. Disease activity was assessed

using the British Isles Lupus Assessment Group (BILAG) system, and

serum levels of BLyS and autoantibodies to dsDNA and extractable

nuclear antigens (ENA) measured by ELISA. Serum immunoglobulins and

anti-dsDNA antibodies were assessed for expression of the 9G4 idiotope

(indicating VH4–34 germline gene origin).

Results: Following BCDT, all patients depleted in the peripheral blood

and improved clinically for 3 months. Pre-BCDT BLyS levels were

quantifiable (median 1.9 ng/ml) in 18/25 patients and rose in most

patients at 3 months post-BCDT (median 4.15 ng/ml). Nine patients, all

with quantifiable pre-BCDT serum BLyS, experienced a disease flare

within 1 year. This group of patients was more likely to harbour

anti-Ro/SSA antibodies (odds ratio 1.76; p = 0.06) with higher serum

levels (p = 0.0027; Mann–Whitney U test). Serum levels of

anti-ribonucleoprotein (RNP)/Sm were also higher in this group

(p<0.05). Expression of VH4–34 by serum immunoglobulins and anti-dsDNA

antibodies had no predictive value for the length of clinical

response.

Conclusions: Patients with SLE with an expanded autoantibody profile

and raised BLyS levels at baseline had shorter clinical responses to

BCDT. This may reflect a greater propensity to, and degree of, epitope

spreading in such patients and suggests that treatment regimens beyond

BCDT may be necessary to induce long-lasting clinical remissions in

these individuals.

http://ard.bmj.com/cgi/content/abstract/67/7/1011?etoc

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