Leher H, Zaragoza F, Taherzadeh S, Alizadeh H, Niederkorn J Y
Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX, 75235-9057, USA.
Exp Eye Res. 1999 Jul;69(1):75-84. doi: 10.1006/exer.1999.0678.
Acanthamoeba keratitis is a rare, yet sight-threatening corneal infection. Ocular infection does not appear to induce protective immunity as repeated corneal infections occur in both humans and experimental animals. However, we have recently demonstrated that activation of the common mucosal immune system by oral immunization with Acanthamoeba antigens protects both Chinese hamsters and pigs against ocular infection with A. castellanii. Protection correlates closely with the appearance of anti- Acanthamoeba antibodies in the tears. To test the hypothesis that oral immunization induces specific protective IgA antibodies, two monoclonal IgA antibodies specific for Acanthamoeba antigens were generated. Both antibodies detected epitopes on the surface of fixed Acanthamoeba trophozoites. When delivered intraperitoneally, one monoclonal antibody (14E4) was detected in stool and tear samples. This clone also protected naive animals against ocular challenge with Acanthamoeba trophozoites (43% infection rate compared to a 91% infection rate in animals receiving control IgA). In vitro functional studies showed that neither antibody induced encystment or directly killed Acanthamoeba trophozoites. However, both monoclonal anti- Acanthamoeba IgA antibodies produced a three-fold inhibition in the adherence of trophozoites to corneal epithelial cells in vitro. These data show that monoclonal anti- Acanthamoeba IgA antibodies can protect against Acanthamoeba keratitis and suggest that this occurs by inhibiting adhesion of the parasite to the corneal epithelium.
棘阿米巴角膜炎是一种罕见但会威胁视力的角膜感染。眼部感染似乎不会诱导保护性免疫，因为人类和实验动物都会发生反复的角膜感染。然而，我们最近证明，通过用棘阿米巴抗原进行口服免疫激活共同黏膜免疫系统，可保护中国仓鼠和猪免受卡氏棘阿米巴的眼部感染。保护作用与泪液中抗棘阿米巴抗体的出现密切相关。为了验证口服免疫诱导特异性保护性IgA抗体的假设，制备了两种针对棘阿米巴抗原的单克隆IgA抗体。两种抗体均能检测到固定棘阿米巴滋养体表面的表位。当腹腔注射时，在粪便和泪液样本中检测到一种单克隆抗体（14E4）。该克隆还保护未感染动物免受棘阿米巴滋养体的眼部攻击（感染率为43%，而接受对照IgA的动物感染率为91%）。体外功能研究表明，两种抗体均未诱导包囊形成或直接杀死棘阿米巴滋养体。然而，两种抗棘阿米巴单克隆IgA抗体在体外均能使滋养体与角膜上皮细胞的黏附受到三倍的抑制。这些数据表明，抗棘阿米巴单克隆IgA抗体可预防棘阿米巴角膜炎，提示其作用机制是抑制寄生虫与角膜上皮的黏附。
