Article Text

other Versions

PDF
Extended report
Persistence of immunoglobulin-producing cells in parotid salivary glands of patients with primary Sjögren's syndrome after B cell depletion therapy
  1. Nishath Hamza1,
  2. Hendrika Bootsma1,
  3. Saravanan Yuvaraj2,
  4. Fred K L Spijkervet3,
  5. Erlin A Haacke4,
  6. Rodney P E Pollard3,
  7. Annie Visser1,2,
  8. Arjan Vissink3,
  9. Cees G M Kallenberg1,
  10. Frans G M Kroese1,2,
  11. Nicolaas A Bos1,2
  1. 1Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
  2. 2Department of Cell Biology, Section Immunology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
  3. 3Department of Oral and Maxillofacial Surgery, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
  4. 4Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
  1. Correspondence to Nicolaas A Bos, University Medical Center Groningen, University of Groningen, Rheumatology and Clinical Immunology, Groningen 9700 RB, Netherlands; n.a.bos{at}umcg.nl

Abstract

Objectives To assess the persistence of immunoglobulin-producing cell populations in the parotid salivary glands of patients with primary Sjögren'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.

Statistics from Altmetric.com

Footnotes

  • Funding Dutch Arthritis Foundation.

  • Competing interests None.

  • Ethics approval University Medical Center Groningen.

  • Provenance and peer review Not commissioned; externally peer reviewed.

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.