Persistence of immunoglobulin-producing cells in parotid salivary glands of patients with primary Sjogren's syndrome after B cell depletion therapy

Nishath Hamza, Hendrika Bootsma, Saravanan Yuvaraj, Fred K. L. Spijkervet, Erlin A. Haacke, Rodney P. E. Pollard, Annie Visser, Arjan Vissink, Cees G. M. Kallenberg, Frans G. M. Kroese, Nicolaas A. Bos*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

39 Citations (Scopus)

Abstract

Objectives To assess the persistence of immunoglobulin-producing cell populations in the parotid salivary glands of patients with primary Sjogren's syndrome (pSS) after B cell depletion therapy with rituximab.

Methods Thirteen patients with pSS and four control patients were included in this study. Patients with pSS were treated with rituximab or placebo. Sequence analysis was carried out on IgA- and IgG-encoding transcripts extracted from parotid salivary gland biopsy specimens taken before treatment and at 12-16 and 36-52 weeks after treatment.

Results At baseline, many clonally related sequences were seen in patients with pSS. The number of clonal expansions was significantly higher in patients with pSS than in control patients. Clonal expansions were composed of IgA- and/or IgG-expressing cells. Rituximab did not significantly alter the degree of clonal expansions. Groups of clonally related cells had members which were shared between biopsy specimens taken before and after treatment. Mutation frequencies of immunoglobulin sequences from clonally related cells in patients with pSS were higher after treatment.

Conclusions Rituximab treatment does not alter the characteristic features of increased clonal expansions seen in the parotid salivary glands of patients with pSS. The presence of clonally related immunoglobulin-producing cells before and after rituximab treatment strongly suggests that immunoglobulin-producing cells persist in salivary glands of patients with pSS despite B cell depletion. The presence of mixed isotype expression within groups of clonally related cells indicates local class switching in salivary glands of patients with pSS. Persistent immunoglobulin-producing cells may underlie disease relapse after treatment.

Original languageEnglish
Pages (from-to)1881-1887
Number of pages7
JournalAnnals of the Rheumatic Diseases
Volume71
Issue number11
DOIs
Publication statusPublished - Nov-2012

Keywords

  • SYSTEMIC-LUPUS-ERYTHEMATOSUS
  • RITUXIMAB TREATMENT
  • PLASMA-CELLS
  • LYMPHOID-TISSUE
  • DOUBLE-BLIND
  • BONE-MARROW
  • FOLLOW-UP
  • MEMORY
  • IGA
  • IMMUNOTHERAPY

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