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Interleukin-21 rest...
Interleukin-21 restores immunoglobulin production ex vivo in patients with common variable immunodeficiency and selective IgA deficiency
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Borte, S (författare)
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- Pan-Hammarstrom, Q (författare)
- Karolinska Institutet
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Liu, CH (författare)
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Sack, U (författare)
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Borte, M (författare)
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Wagner, U (författare)
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Graf, D (författare)
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- Hammarstrom, L (författare)
- Karolinska Institutet
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(creator_code:org_t)
- American Society of Hematology, 2009
- 2009
- Engelska.
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 114:19, s. 4089-4098
- Relaterad länk:
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http://kipublication...
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https://doi.org/10.1...
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Abstract
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- Interleukin-21 (IL-21) is an important promoter for differentiation of human B cells into immunoglobulin (Ig)–secreting cells. The objective of this study was to evaluate an IL-21–based approach to induce immunoglobulin production in B cells from patients with common variable immunodeficiency (CVID) or selective IgA deficiency (IgAD). We show that a combination of IL-21, IL-4, and anti-CD40 stimulation induces class-switch recombination to IgG and IgA and differentiation of Ig-secreting cells, consisting of both surface IgG+ (sIgG+) and sIgA+ B cells and CD138+ plasma cells, in patients with CVID or IgAD. Stimulation with IL-21 was far more effective than stimulation with IL-4 or IL-10. Moreover, spontaneous apoptosis of CD19+ B cells from patients with CVID or IgAD was prevented by a combination of IL-21, IL-4, and anti-CD40 stimulation. Analysis of IL-21 and IL-21 receptor (IL-21R) mRNA expression upon anti-CD3 stimulation of T cells, however, showed no evidence for defective IL-21 expression in CVID patients and sequencing of the coding regions of the IL21 gene did not reveal any mutations, suggesting a regulatory defect. Thus, our work provides an initial basis for a potential therapeutic role of IL-21 to reconstitute immunoglobulin production in CVID and IgAD.
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