Genetic diagnosis and immunoglobulin A receptor targeting therapy for periodontitis

牙周炎的基因诊断及免疫球蛋白A受体靶向治疗

• 批准号: 13557189
• 负责人: KOBAYASHI Tetsuo
• 金额: $ 7.49万
• 依托单位: NIIGATA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13557189/
• 关键词: Periodontitis; Polymorphism; Immunoglobulin; FcαR; Bispecific antibody; Porphyromonas gingivalis; Neutrophils; Targeting therapy; 免疫グロブリンA; ターゲッテイング療法; r40kDa OMP; Porhyromomas gingivalis

-1.Genetic diagnosis of periodontisis risk :Sequence analyses of immunoglobulin A and G Fc receptor (neutrophil-specific FcαRI, CD89 and B cell-specific FcγRIIB, CD32) indicated one and seven single-nucleotide substitutions, respectively. Of these polymorphisms, FcαRI nt 324A/G and FcγRIIB nt 775T/C have been shown to be associated with aggressive periodontitis risk. Neutrophils (PMN) from peripheral blood and gingival crevicular fluid (GCF) of periodontitis patients exhibited a decreased phagocytosis in the nt 324 A/A as compared to the nt 324 G/G patients. These results suggest FcαRI nt 324A/A patients to be high-susceptibility to aggressive periodontitis.-2.Immunoglobulin A receptor targeting therapy :The bispecific antibody (BsAb) was constructed from anti-Porphyromonas gingivalis and anti-FcαRI monoclonal antibody (MAb). Flow cytometric analyses showed opsonic activity for GCF PMN to be comparable between BsAb and control anti-P. gingivalis MAb. However, a BsAb significantly promoted phagocytosis and killing activity of GCF PMN, which exhibiting higher FcαRI expression levels than PB PMN. These data suggest BsAb targeting toward GCF PMN FcαRI to be effective for improvement of antibacterial immunity in periodontitis patients.

1.牙周病风险的基因诊断：免疫球蛋白A和G Fc受体（嗜中性粒细胞特异性FcαRI，CD 89和B细胞特异性FcγRIIB，CD 32）的序列分析分别显示1个和7个单核苷酸替换。在这些多态性中，FcαRI nt 324 A/G和FcγRIIB nt 775 T/C已被证明与侵袭性牙周炎风险相关。牙周炎患者外周血和龈沟液中的中性粒细胞（PMN）对nt 324 A/A的吞噬作用明显低于nt 324 G/G患者。提示FcαRI nt 324 A/A患者对侵袭性牙周炎易感。2.免疫球蛋白A受体靶向治疗：用抗牙龈卟啉单胞菌（Porphyromonas gingivalis）和抗Fc αRI单克隆抗体（MAb）构建双特异性抗体（BsAb）。流式细胞术分析显示，BsAb和对照抗牙龈卟啉单克隆抗体对GCF PMN的调理活性相当。但BsAb能显著促进GCF PMN的吞噬和杀伤活性，其FcαRI表达水平高于PB PMN。这些数据表明，针对GCF PMN FcαRI的BsAb可有效提高牙周炎患者的抗菌免疫力。

项目成果

Yasuko Shimada et al.: "Association of tumor necrosis factor receptor type 2 +587 gene polymorphism with severe chronic periodontitis"Journal of Clinical Periodontology. (in press). (2004)

Yasuko Shimada等：“肿瘤坏死因子受体2587型基因多态性与严重慢性牙周炎的关联”临床牙周病学杂志。

T.Kobayashi, S.Ito, K.Yamamoto, H.Hasegawa, N.Sugita, T.Kuroda, S.Kaneko, I.Narita, K.Yasuda, M.Nakano, F.Gejyo, H.Yoshie.: "Risk of Periodontitis in Systemic Lupus Erythematosus Is Associated with Fcγ Receptor Polymorphisms.."Journal of Periodontology. V

T.小林、S.Ito、K.Yamamoto、H.Hasekawa、N.Sugita、T.Kuroda、S.Kaneko、I.Narita、K.Yasuda、M.Nakano、F.Gejyo、H.Yoshie。：“系统性红斑狼疮的牙周炎风险与 Fcγ 受体多态性相关......“牙周病学杂志。V

K.Yamamoto, T.Kobayashi, S.Grossi, AW.Ho, R.J.Genco, H.Yoshie, E.De Nardin.: "Association of Fcγ receptor IIa genotype with chronic periodontitis in Caucasians"Journal of Periodontology. (in press). (2004)

K.Yamamoto、T.Kobayashi、S.Grossi、AW.Ho、R.J.Genco、H.Yoshie、E.De Nardin.：“Fcγ 受体 IIa 基因型与白种人慢性牙周炎的关联”牙周病学杂志（正在出版）。 (2004)

JR.Gonzales, T.Kobayashi, J.Michel, M.Mann, H.Yoshie, J.Meyle: "Interleukin-4 gene polymorphisms in Japanese and Caucasian patients with aggressive periodontitis"Journal of Clinical Periodontology. (in press). (2004)

JR.Gonzales、T.Kobayashi、J.Michel、M.Mann、H.Yoshie、J.Meyle：“日本和白人侵袭性牙周炎患者的白细胞介素 4 基因多态性”临床牙周病学杂志。

Keiko Yasuda et al.: "FcγRIIB Gene Polymorphisms in Japanese Periodontitis Patients"Genes and Immunity. Vol.4. 541-546 (2003)

Keiko Yasuda 等：“日本牙周炎患者的 FcγRIIB 基因多态性”基因与免疫，第 4 卷（2003 年）。