FCGR2A polymorphism is correlated with clinical outcome after immunotherapy of neuroblastoma with anti-GD2 antibody and granulocyte macrophage colony-stimulating factor
JOURNAL OF CLINICAL ONCOLOGY
Authors: Cheung, NKV; Sowers, R; Vickers, AJ; Cheung, IY; Kushner, BH; Gorlick, R
Abstract
Purpose Anti-GD2 murine IgG3 antibody 3F8 kills neuroblastoma cells by antibody-dependent cell-mediated cytotoxicity (ADCC). Granulocyte macrophage colony-stimulating factor (GM-CSF) enhances phagocyte-mediated ADCC. The differential affinity of the human FCGR polymorphic alleles for 3F8 may influence the effectiveness of antibody immunotherapy. Patients and Methods The entire cohort of high risk neuroblastoma patients (N = 136) treated on protocol using 3F8 and GM-CSF were the subjects of this analysis. Tumor response was measured by standard clinical tools plus sensitive molecular monitoring using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Polymorphic alleles of FCGR2A and FCGR3A were determined by PCR plus direct sequencing using genomic DNA samples obtained from marrow or blood of patients. Results FCGR2A (R/R) genotype correlated with progression-free survival for the entire cohort (P = .049) and for the subset of patients with no history of prior relapse (P = .023). FCGR2A (R/R) also correlated with marrow remission 2.5 months after treatment initiation: by histology (P = .021 and P = .036, for the entire cohort and the subset, respectively) and by qRT-PCR (P = .052 and P = .033, respectively). Conclusion The favorable outcome associated with FCGR2A (R/R) genotype is consistent with the proposed role of FCGR2A and phagocyte-mediated ADCC in 3F8 plus GM-CSF immunotherapy.
A genome-wide association study identifies three new risk loci for Kawasaki disease
NATURE GENETICS
Authors: Onouchi, Yoshihiro; Ozaki, Kouichi; Burns, Jane C.; Shimizu, Chisato; Terai, Masaru; Hamada, Hiromichi; Honda, Takafumi; Suzuki, Hiroyuki; Suenaga, Tomohiro; Takeuchi, Takashi; Yoshikawa, Norishige; Suzuki, Yoichi; Yasukawa, Kumi; Ebata, Ryota; Higashi, Kouji; Saji, Tsutomu; Kemmotsu, Yasushi; Takatsuki, Shinichi; Ouchi, Kazunobu; Kishi, Fumio; Yoshikawa, Tetsushi; Nagai, Toshiro; Hamamoto, Kunihiro; Sato, Yoshitake; Honda, Akihito; Kobayashi, Hironobu; Sato, Junichi; Shibuta, Shoichi; Miyawaki, Masakazu; Oishi, Ko; Yamaga, Hironobu; Aoyagi, Noriyuki; Iwahashi, Seiji; Miyashita, Ritsuko; Murata, Yuji; Sasago, Kumiko; Takahashi, Atsushi; Kamatani, Naoyuki; Kubo, Michiaki; Tsunoda, Tatsuhiko; Hata, Akira; Nakamura, Yusuke; Tanaka, Toshihiro; Abe, Jun; Kobayashi, Tohru; Arakawa, Hirokazu; Ichida, Fukiko; Nomura, Yuichi; Miura, Masaru; Ikeda, Kazuyuki; Hara, Toshiro; Fukazawa, Ryuji; Ogawa, Shunichi; Hamaoka, Kenji; Newburger, Jane W.; Baker, Annette L.; Rowley, Anne H.; Shulman, Stanford T.; Melish, Marian E.; Mason, Wilbert H.; Takahashi, Masato; Tremoulet, Adriana H.
Abstract
We performed a genome-wide association study (GWAS) of Kawasaki disease in Japanese subjects using data from 428 individuals with Kawasaki disease (cases) and 3,379 controls genotyped at 473,803 SNPs. We validated the association results in two independent replication panels totaling 754 cases and 947 controls. We observed significant associations in the FAM167A-BLK region at 8p22-23 (rs2254546, P = 8.2 x 10(-21)), in the human leukocyte antigen (HLA) region at 6p21.3 (rs2857151, P = 4.6 x 10(-11)) and in the CD40 region at 20q13 (rs4813003, P = 4.8 x 10(-8)). We also replicated the association of a functional SNP of FCGR2A (rs1801274, P = 1.6 x 10(-6)) identified in a recently reported GWAS of Kawasaki disease. Our findings provide new insights into the pathogenesis and pathophysiology of Kawasaki disease.
COA
Publication 
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