Chronic signs of memory B cell activation in patients with Behçet's disease are partially restored by anti-tumour necrosis factor treatment

Tim B. Van Der Houwen, P. Martin Van Hagen, Wilhemina M. C. Timmermans, Sophinus J W Bartol, King H. Lam, Jasper H. Kappen, Menno C. van Zelm, Jan A M Van Laar

Research output: Contribution to journalArticleResearchpeer-review

9 Citations (Scopus)

Abstract

OBJECTIVES: Behçet's disease (BD), an auto-inflammatory vasculitis with oro-genital ulcerations, skin lesions and uveitis, is regarded as T cell mediated. A successful trial with rituximab suggests an additive role for B cells in the pathogenesis. Therefore, we studied B cell abnormalities in BD patients and the effect of TNF-blocking therapy.

METHODS: B cells in blood (n = 36) and tissue (n = 6) of BD patients were analysed with flow cytometry and/or immunohistochemistry and compared with healthy controls (n = 22). BD current activity form (BDCAF) in relation to B cell somatic hypermutations (SHMs) and immunoglobulin class-switching were studied.

RESULTS: Thirty-six patients (17 males) were included, mean age 44 years, average disease duration 10 years and mean BDCAF 2.7. Blood B cell numbers were significantly lower in patients than in controls (P = 0.0061), mostly due to decreased CD27+ memory B cells expressing IgM (P = 0.0001), IgG (P = 0.0002) and IgA (P = 0.0038) B cell subsets. CD27+ IgA+ B cells showed the highest magnitude of decrease in active disease, measured with BDCAF (P = 0.02). CD27+ IgM+ IgD+ B cells were impaired in replication history (P = 0.0133) and selection of SHM, whereas IgA+ B cells carried elevated SHM levels (P = 0.04) and lower IgA2 subclass usage (P = 0.0004) than controls. Immunohistochemistry revealed B cells in tissue of active mucosal ulcers. In adalimumab-treated patients, blood B cells were similar to controls.

CONCLUSION: We show significant deviations in the memory B cell compartment, related to disease activity and therapeutic efficacy. Pronounced molecular impairments were seen in the fast-responding IgM+-memory and the mucosal IgA+-memory B cells. Because of the demonstrated abundance of B cells in affected tissue, we hypothesize relocation of memory B cells to the site of inflammation could account for the deviations found in blood of BD patients. These peripheral B cells are easily accessible as a marker to monitor therapeutic efficacy.

Original languageEnglish
Pages (from-to)134-144
Number of pages11
JournalRheumatology
Volume56
Issue number1
DOIs
Publication statusPublished - 1 Jan 2017

Keywords

  • Behc¸ et’s disease
  • B cells
  • TNF blockers
  • memory B cell formation

Cite this