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KAKEN_24791175seika.pdf
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Title |
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天疱瘡の新治療に向けたIgGサブクラス解析とIgG4除去療法
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テンポウソウ ノ シンチリョウ ニ ムケタ IgG サブクラス カイセキ ト IgG4 ジョキョ リョウホウ
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Tenposo no shinchiryo ni muketa IgG sabukurasu kaiseki to IgG4 jokyo ryoho
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IgG subclass analysis and IgG4 depletion therapy for pemphigus
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舩越, 建
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フナコシ, タケル
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Funakoshi, Takeru
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慶應義塾大学・医学部・助教
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Research team head
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科研費研究者番号 : 80365353
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2014
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科学研究費補助金研究成果報告書
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2013
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天疱瘡は表皮細胞の細胞間接着因子であるデスモグレイン(Dsg)に対する自己抗体によって生じる疾患で、自己抗体についてのさまざまな解析が進められている。われわれが行った天疱瘡におけるIgGサブクラスの解析の結果、総IgG中のIgG4の割合の増加が示され、更に抗Dsg抗体のIgG4サブクラスの上昇が確認された。また、患者血清からIgG4を除去することによる病原性の低下を、表皮細胞解離アッセイで確認した。同一患者における疾患活動性とIgG4の相関について、疾患活動期・寛解期におけるIgG4を測定し複数の患者で検討した結果、Dsg特異的IgG4濃度は活動期で明らかに高いことが分かった(p=0.04)。
Pemphigus is an autoimmune blistering disease caused by circulating antibodies against desmogleins (Dsg) which are cell-cell adhesion protein in the epidermis. We recently established anti-Dsg IgG subclass ELISA method and we showed that Dsg-specific autoantibodies are enriched in IgG4. Addition to that total serum IgG4 was enriched in patients with pemphigus. Furthermore, IgG4 depletion of pemphigus sera reduced pathogenicity in a keratinocyte dissociation assay. The median serum concentration of Dsg-specific IgG4 was significantly higher in pemphigus patients during active disease compared to patients in remission(p=0.04). Memory B cell populations were enriched for surface-IgG4 positive cells in pemphigus compared to unaffected individuals.
IgG4 could be depleted by immunoadsorption or by selective depletion of surface-IgG4 memory B cells, and which we have shown can be bound and hence potentially targeted based on surface IgG4 expression.
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研究種目 : 若手研究(B)
研究期間 : 2012~2013
課題番号 : 24791175
研究分野 : 医歯薬学
科研費の分科・細目 : 内科系臨床医学・皮膚科学
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