FcαRI (CD89) alleles determine the proinflammatory potential of serum IgA

Jianming Wu, Chuanyi Ji, Fenglong Xie, Carl D. Langefeld, Kun Qian, Andrew W. Gibson, Jeffrey C. Edberg, Robert P. Kimberly

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

The human IgA FcR (FcαRI; CD89) mediates a variety of immune system functions including degranulation, endocytosis, phagocytosis, cytokine synthesis, and cytokine release. We have identified a common, nonsynonymous, single nucleotide polymorphism (SNP) in the coding region of CD89 (844A→G) (rs16986050), which changes codon 248 from AGC (Ser248) to GGC (Gly248) in the cytoplasmic domain of the receptor. The two different alleles demonstrate significantly different FcαRI-mediated intracellular calcium mobilization and degranulation in rat basophilic leukemia cells and cytokine production (IL-6 and TNF-α) in murine macrophage P388D1 cells. In the absence of FcR γ-chain association in P388D1 cells, the Ser 248-FcαRI allele does not mediate cytokine production, but the Gly248-FcαRI allele retains the capacity to mediate a robust production of proinflammatory cytokine. This allele-dependent difference is also seen with FcαRI-mediated IL-6 cytokine release by human neutrophils ex vivo. These findings and the enrichment of the proinflammatory Gly 248-FcαRI allele in systemic lupas erythematosus populations in two ethnic groups compared with their respective non-systemic lupus erythematosus controls suggest that FcαRI (CD89) α-chain alleles may affect receptor-mediated signaling and play an important role in the modulation of immune responses in inflammatory diseases.

Original languageEnglish (US)
Pages (from-to)3973-3982
Number of pages10
JournalJournal of Immunology
Volume178
Issue number6
DOIs
StatePublished - Mar 15 2007

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    Wu, J., Ji, C., Xie, F., Langefeld, C. D., Qian, K., Gibson, A. W., Edberg, J. C., & Kimberly, R. P. (2007). FcαRI (CD89) alleles determine the proinflammatory potential of serum IgA. Journal of Immunology, 178(6), 3973-3982. https://doi.org/10.4049/jimmunol.178.6.3973