Kakavanos Revecca, Lehn Pierre, Callebaut Isabelle, Meikle Peter J, Parkinson-Lawrence Emma J, Hopwood John J, Brooks Doug A
Lysosomal Diseases Research Unit, Department of Genetic Medicine, Children Youth and Women's Health Service, 72 King William Road, North Adelaide, Adelaide, SA 5006, Australia.
FEBS Lett. 2006 Jan 9;580(1):87-92. doi: 10.1016/j.febslet.2005.11.053. Epub 2005 Dec 6.
Enzyme replacement therapy (ERT) has proven to be an effective therapy for some lysosomal storage disorder (LSD) patients. A potential complication during ERT is the generation of an immune response against the replacement protein. We have investigated the antigenicity of two distantly related glycosidases, alpha-glucosidase (Pompe disease or glycogen storage disease type II, GSD II), and alpha-L-iduronidase (Hurler syndrome, mucopolysaccharidosis type I, MPS I). The linear sequence epitope reactivity of affinity purified polyclonal antibodies to recombinant human alpha-glucosidase and alpha-L-iduronidase was defined, to both glycosidases. The polyclonal antibodies exhibited some cross-reactive epitopes on the two proteins. Moreover, a monoclonal antibody to the active site of alpha-glucosidase showed cross-reactivity with a catalytic structural element of alpha-L-iduronidase. In a previous study, in MPS I patients who developed an immune response to ERT, this same site on alpha-L-iduronidase was highly antigenic and the last to tolerise following repeated enzyme infusions. We conclude that glycosidases can exhibit cross-reactive epitopes, and infer that this may relate to common structural elements associated with their active sites.
酶替代疗法（ERT）已被证明是治疗某些溶酶体贮积症（LSD）患者的有效疗法。ERT期间的一个潜在并发症是产生针对替代蛋白的免疫反应。我们研究了两种远缘糖苷酶的抗原性，即α-葡萄糖苷酶（庞贝病或糖原贮积病II型，GSD II）和α-L-艾杜糖醛酸酶（Hurler综合征，黏多糖贮积症I型，MPS I）。确定了亲和纯化的多克隆抗体对重组人α-葡萄糖苷酶和α-L-艾杜糖醛酸酶的线性序列表位反应性，这两种糖苷酶都有。多克隆抗体在这两种蛋白质上表现出一些交叉反应表位。此外，一种针对α-葡萄糖苷酶活性位点的单克隆抗体与α-L-艾杜糖醛酸酶的一个催化结构元件表现出交叉反应性。在先前的一项研究中，在对ERT产生免疫反应的MPS I患者中，α-L-艾杜糖醛酸酶上的这个相同位点具有高度抗原性，并且在反复输注酶后是最后一个被耐受的位点。我们得出结论，糖苷酶可以表现出交叉反应表位，并推断这可能与与其活性位点相关的共同结构元件有关。
