Dendritic cells of IgA nephropathy patients have an impaired capacity to induce IgA production in naïve B cells

Jan Willem Eijgenraam, Andrea Woltman, Sylvia W.A. Kamerling, Francine Briere, Johan W. De Fijter, Mohamed R. Daha, Cees Van Kooten*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

11 Citations (Scopus)

Abstract

Background. IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide, characterized by mesangial IgA1 deposits. We have previously demonstrated that IgAN patients have a hampered IgA immune respons after mucosal challenge with a neoantigen. Dendritic cells are critically involved in the initiation of humoral immune responses, not only via activation of T-helper cells, but also via direct effect on naïve B cells. The aim of this study was to investigate the capacity of dendritic cells from IgAN patients to regulate IgA production. Methods. Dendritic cells were generated by culturing mono-cytes for 7 days in the presence of interleukin (IL)-4 and granulocyte macrophage-colony-stimulating factor (GM-CSF). Dendritic cells from either IgAN patients (N = 12) or controls (N = 12) were cultured for 14 days with naïve B cells in the presence of CD40L-transfected mouse flbroblasts (L-CD40L cells) and medium with or without IL-2 or IL-10. Supernatants were tested for the presence of immunoglobulins by specific enzyme-linked immunosorbent assay (ELISA). Results. In the presence of CD40L and IL-10, dendritic cells were able to increase immunoglobulin production by naïve B cells. Dendritic cells of IgAN patients induced significantly (P = 0.026) less IgA production than dendritic cells of control persons (2.30 μg/mL vs. 5.24 μg/mL), whereas no differences were found in the IgG and IgM production. When dendritic cells were replaced by supernatant of CD40L-stimulated dendritic cells of patients and controls, IgA production was increased, but no difference was seen between the two groups. Conclusion. In the present study we show that dendritic cells of IgAN patients have an impaired capacity to induce IgA production in naïve B cells, which might explain the observed IgA hyporesponse upon mucosal challenge with a neoantigen.

Original languageEnglish
Pages (from-to)1604-1612
Number of pages9
JournalKidney International
Volume68
Issue number4
DOIs
Publication statusPublished - Oct 2005
Externally publishedYes

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