Epitope analysis for anti-laminin 332 antibodies in sera from patients with mucous membrane pemphigoid

• Project/Area Number: 17K16357
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Dermatology
• Research Institution: Kurume University
• Principal Investigator: Koga Hiroshi 久留米大学, 医学部, 講師 (40461412)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: ラミニン332 / 7型コラーゲン / エピトープ / 免疫学 / 蛋白質

Outline of Final Research Achievements

While epitope analysis for anti-laminin 332 antibodies in sera from patients with mucous membrane pemphigoid was initially planned, other group reported a similar study during a period of this study. Therefore, we changed the purpose of this study to precise detection of the binding site on laminin beta 3 to type VII collagen. In result, we detected that the binding site was located in the mid portion of LE domain in laminin beta 3 using several recombinant proteins of laminin beta 3 and type VII collagen. We are planning to perform a precise detection of the site and evaluate the inhibitory effect of antibodies in the patients’ sera on binding of laminin beta 3 and type VII collagen.

Academic Significance and Societal Importance of the Research Achievements

粘膜類天疱瘡患者血中のラミニン332抗体が水疱を生じさせることは、実験的には証明されているが、具体的にどのような機序で水疱が生じるのかは明らかにされていない。今回、皮膚の接着に重要なラミニン332と7型コラーゲンの結合部位を特定し、その部位で抗体が両者の接着を阻害するかどうかを検討することで、水疱形成の機序を解明する研究となっている。この結果は、粘膜類天疱瘡患者において何故水疱が生じるのかを解明する一助となる。