A novel polymorphism of FcgammaRIIIa (CD16) alters receptor function and predisposes to autoimmune disease.

Abstract

Abstract

The “less-is-more” in therapeutic antibodies: Afucosylated anti-cancer antibodies with enhanced antibody-dependent cellular cytotoxicity

“…demonstrated that the glycosylation at Asn162 of FcγRIII is not essential for the expression of the receptor; however, this glycosylation site is conserved among all FcγRIIIs (or the equivalent) in all mammals studied 19 . Furthermore, in all FcγRs, the regions that interact with the antibody are highly conserved, yet all other receptors lack this glycosylation site 9 .…”

“…For example, under similar experimental conditions, FcγRIIIa-V158 demonstrated an approximately 10-fold higher affinity for IgG than FcγRIIIa-F158 20 . Cells expressing the FcγRIIIa-V158 allele mediate ADCC more effectively 19 . In anti-epidermal growth factor receptor (EGFR) antibody-treated colorectal cancer patients, the clinical outcome was strongly associated with the FcγRIIIa polymorphisms.…”

Analysis of gene expression profiles in human systemic lupus erythematosus using oligonucleotide microarray

“…1 Epidemiological studies suggest a strong genetic component for susceptibility to SLE 2,3 and multiple genes including those that affect immune complex deposition, and the MHC have been implicated in pathogenesis. [4][5][6] Several whole-genome linkage studies have also been reported suggesting about 20 SLE susceptibility loci. [7][8][9][10] Together, these studies suggest that SLE is a polygenic disorder with contributions from multiple genes, each one of which has a modest effect.…”

FcγR expression on NK cells influences disease severity in rheumatoid arthritis

“…8 We have recently found that FcgRIIc is predominantly expressed on NK cells and that it is able to trigger NK cell lysis of antibody-coated target cells and cytokine production. [9][10][11] Allelic polymorphisms of FcgR genes have been described 9,[12][13][14][15] that affect the function of cells of the innate immune system including FcgRIIIA, 14,16 FcgRIIA, 17 FcgRIIC, 7,18 and FcgRIA. 19 In general, these polymorphisms have been shown to alter the ligand binding specificity of particular FcgR, such as FcgRIIa, 17 and FcgRIIIa.…”

“…19 In general, these polymorphisms have been shown to alter the ligand binding specificity of particular FcgR, such as FcgRIIa, 17 and FcgRIIIa. 14,16 These allelic polymorphisms have proved to be clinically significant in infectious 20,21 and autoimmune 12,13,[22][23][24] diseases.…”