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Bacterial DNA motifs trigger ANCA production in ANCA-associated vasculitis in remission

Tadema, H., Abdulahad, W. H., Lepse, N., Stegeman, C. A., Kallenberg, C. G. M. & Heeringa, P., Apr-2011, In : Rheumatology. 50, 4, p. 689-696 8 p.

Research output: Contribution to journalArticleAcademicpeer-review

Methods. Expression of Toll-like receptor 9 (TLR9) by B lymphocytes from AAV patients and controls was assessed. Peripheral blood mononuclear cells were isolated from 23 PR3-ANCA and 15 MPO-ANCA patients (33 quiescent, 5 active disease) and 14 healthy controls, and cultured for 12 days in the presence of cytosine-phosphate-guanine oligodeoxynucleotide (CpG-ODN) and IL-2. B-lymphocyte activation, differentiation, immunoglobulin production and in vitro ANCA production were studied.

Results. TLR9 expression by B lymphocytes was comparable in AAV patients and controls. B lymphocytes were activated and differentiated towards a plasma cell phenotype in response to CpG-ODN and IL-2. ANCA were produced in vitro by 13 out of 23 PR3-ANCA patients and 3 out of 15 MPO-ANCA patients.

Conclusions. We conclude that ANCA-producing B lymphocytes can be present in the peripheral blood of AAV patients during remission. These autoreactive B lymphocytes are triggered by CpG-ODN and IL-2 to produce ANCA in vitro. CpG motifs may trigger the production of ANCA in vivo, contributing to the development of relapses in AAV.

Original languageEnglish
Pages (from-to)689-696
Number of pages8
JournalRheumatology
Volume50
Issue number4
Publication statusPublished - Apr-2011

    Keywords

  • Anti-neutrophil cytoplasmic antibodies, B lymphocytes, Bacterial DNA, Cytosine-phosphate-guanine oligodeoxynucleotide, Vasculitis, SYSTEMIC-LUPUS-ERYTHEMATOSUS, NAIVE B-CELLS, WEGENERS-GRANULOMATOSIS, PERIPHERAL-BLOOD, CRESCENTIC GLOMERULONEPHRITIS, MONOCLONAL-ANTIBODIES, STAPHYLOCOCCUS-AUREUS, RHEUMATOID-ARTHRITIS, NASAL CARRIAGE, CYCLOPHOSPHAMIDE

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