Fcalphari (Cd89) Alleles Determine the Proinflammatory Potential of Serum Iga.
From: Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, 1825 University Boulevard, Birmingham, AL 35294, USA.
Journal of immunology (Baltimore, Md. : 1950)
- Publish Date: Mar 2007
- ISSN: 0022-1767
- Volume: 178
- Issue: 6
- Pages: 3973-82
- Medium: Print
- Language: English
- Citation (JAMA): Wu Jianming, Ji Chuanyi, Xie Fenglong, et al. Fcalphari (Cd89) Alleles Determine the Proinflammatory Potential of Serum Iga.. J. Immunol. Mar 2007;178:3973-82
Abstract
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.
Mesh Headings (Keywords): 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
Check for Full Text / PubMed Unique Identifier (PMID): 17339498
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