FcalphaRI (CD89) alleles determine the proinflammatory potential of serum IgA.

Academic Article


  • The human IgA FcR (FcalphaRI; 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 (Ser(248)) to GGC (Gly(248)) in the cytoplasmic domain of the receptor. The two different alleles demonstrate significantly different FcalphaRI-mediated intracellular calcium mobilization and degranulation in rat basophilic leukemia cells and cytokine production (IL-6 and TNF-alpha) in murine macrophage P388D1 cells. In the absence of FcR gamma-chain association in P388D1 cells, the Ser(248)-FcalphaRI allele does not mediate cytokine production, but the Gly(248)-FcalphaRI allele retains the capacity to mediate a robust production of proinflammatory cytokine. This allele-dependent difference is also seen with FcalphaRI-mediated IL-6 cytokine release by human neutrophils ex vivo. These findings and the enrichment of the proinflammatory Gly(248)-FcalphaRI allele in systemic lupus erythematosus populations in two ethnic groups compared with their respective non-systemic lupus erythematosus controls suggest that FcalphaRI (CD89) alpha-chain alleles may affect receptor-mediated signaling and play an important role in the modulation of immune responses in inflammatory diseases.
  • Published In


  • Alleles, Animals, Antigens, CD, Cell Degranulation, Cell Line, Tumor, Endocytosis, Humans, Immunoglobulin A, Interleukin-6, Lupus Erythematosus, Systemic, Mutation, Missense, Neutrophils, Phagocytosis, Polymorphism, Single Nucleotide, Rats, Receptors, Fc, Tumor Necrosis Factor-alpha
  • Digital Object Identifier (doi)

    Author List

  • Wu J; Ji C; Xie F; Langefeld CD; Qian K; Gibson AW; Edberg JC; Kimberly RP
  • Start Page

  • 3973
  • End Page

  • 3982
  • Volume

  • 178