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Regulatory and effector B cell cytokine production in patients with relapsing granulomatosis with polyangiitis

Land, J., Abdulahad, W. H., Sanders, J. S., Stegeman, C. A., Heeringa, P. & Rutgers, A., 4-Apr-2016, In : Arthritis Research and Therapy. 18, 11 p., 84.

Research output: Contribution to journalArticleAcademicpeer-review

Background: B cells are capable of producing regulatory and effector cytokines. In patients with granulomatosis with polyangiitis (GPA), skewing of the pro- and anti-inflammatory cytokine balance may affect the risk of relapse. This study aimed to investigate differences in B cell cytokine production in patients with relapsing GPA and in controls, and determine whether this can aid in relapse prediction.

Methods: Thirteen GPA patients with an upcoming relapse were matched with non-relapsing patients and healthy controls in a retrospective design. The B cell subset distribution was determined from peripheral blood. Cryopreserved peripheral blood mononuclear cells were cultured and intracellular B cell production of regulatory (IL10) and effector (TNF alpha, IFN gamma IL2, IL6) cytokines was assessed. Finally, serum markers associated with B cell activation (sCD27) and migration (CCL19) were determined.

Results: GPA patient samples exhibited significantly lower percentages of TNF alpha+B cells than controls, an effect that was most pronounced in patients about to relapse. B cell capacity for IL10 production was similar in patients and controls. No significant differences were observed for cytokine production in relapsing and non-relapsing GPA patients. TNFa production correlated strongly with IL2, IFN gamma and the percentage of memory B cells. No change in effector cytokines occurred before relapse, while the percentage of IL10+B cells significantly decreased. GPA patients in remission had increased serum levels of CCL19 and sCD27, and sCD27 levels increased upon active disease.

Conclusions: While differences in effector B cell cytokine production were observed between patients and controls, monitoring this in GPA did not clearly distinguish patients about to relapse. Prospective measurements of the regulatory cytokine IL10 may have potential for relapse prediction. Memory B cells appear mainly responsible for effector cytokine production. Increased migration of these cells could explain the decreased presence of TNF alpha+B cells in the circulation.

Original languageEnglish
Article number84
Number of pages11
JournalArthritis Research and Therapy
Volume18
Publication statusPublished - 4-Apr-2016

    Keywords

  • Vasculitis, GPA, Cytokines, B-cells, Relapse, IL10, TNF alpha, CCL19, sCD27, ANCA-ASSOCIATED VASCULITIS, SYSTEMIC-LUPUS-ERYTHEMATOSUS, RHEUMATOID-ARTHRITIS, SOLUBLE CD27, T-CELLS, EXPRESSION, RITUXIMAB, ACTIVATION, ANTIBODY, CYCLOPHOSPHAMIDE

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