Antigen specificity in canine autoimmune haemolytic anaemia
Antigen specificity in canine autoimmune haemolytic anaemia
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DOI：
10.1016/s0165-2427(99)00055-0
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发表时间：
1999-08-02
影响因子：
1.8
通讯作者：
Day, MJ
中科院分区：
文献类型：
--
作者：
Day, MJ
自身免疫性溶血性贫血（AIHA）是犬自身免疫最常见的临床表现，通常表现为急性或慢性发作的严重的、再生性的库姆斯氏阳性贫血。该疾病的发病机制涉及红细胞特异性 IgG 和 IgM 类自身抗体的形成，这些抗体可能会固定补体，导致血管内或血管外溶血。使用从患有 AIHA 的狗的红细胞中洗脱的自身抗体进行的蛋白质印迹和免疫沉淀研究已证明对红细胞糖蛋白和膜阴离子交换分子（条带 3）具有特异性。已通过 ELISA 在血清中鉴定出对细胞骨架分子血影蛋白具有特异性的自身抗体。自身反应性 T 细胞的特异性已在体外使用一组自身抗原（包括完整的红细胞膜、纯化的血型糖蛋白和血影蛋白级分以及一组重叠的 15 聚体血型糖蛋白肽）刺激的大量培养物进行了体外检查。在同一系统中测量对 ConA 和回忆（疫苗抗原）和非回忆（KLH）抗原的对照反应。从 AIHA 恢复的母鹿中获得的 PBMC 持续增殖，对红细胞膜有反应，偶尔对血影蛋白或血型糖蛋白有反应。一些临床正常狗的 PBMC 也对红细胞膜有反应。从与 AIHA 病例密切相关的狗身上获得的 PBMC 给出了最一致的反应，包括在糖蛋白肽刺激下增殖。这些数据表明，正常的狗含有红细胞自身反应性淋巴细胞，并且这些细胞可能在从 AMA 中恢复或对该疾病具有遗传易感性的狗中被引发。 (C) 1999 Elsevier Science B.V. 保留所有权利。
Autoimmune haemolytic anaemia (AIHA) is the most common clinical manifestation of autoimmunity in the dog and generally presents as a profound, regenerative, Coombs' positive anaemia of acute or chronic onset. The disease pathogenesis involves formation of erythrocyte-specific autoantibodies of the IgG and IgM class that may fix complement resulting in intra- or extravascular haemolysis. Western blotting and immunoprecipitation studies using autoantibody eluted from the erythrocytes of dogs with AIHA have demonstrated specificity for erythrocyte glycophorins and the membrane anion-exchange molecule (band 3). Autoantibodies specific for the cytoskeletal molecule spectrin have been identified in serum by ELISA. The specificity of autoreactive T-cells has been examined in vitro using bulk cultures stimulated with a panel of autoantigens including intact erythrocyte membranes, purified glycophorin and spectrin fractions and a panel of overlapping 15-mer glycophorin peptides. Control responses to ConA and recall (vaccine antigens) and non-recall (KLH) antigens were measured in the same system. PBMC obtained from does that had recovered from AIHA consistently proliferated in response to erythrocyte membranes, with occasional responses to spectrin or glycophorin. PBMC from sone clinically normal dogs also responded to erythrocyte membranes. PBMC obtained from dogs closely related to AIHA cases gave the most consistent responses, including proliferation when stimulated by the glycophorin peptides. These data suggest that normal dogs harbour erythrocyte autoreactive lymphocytes, and that these cells may be primed in dogs recovered from AMA or having genetic susceptibility to the disease. (C) 1999 Elsevier Science B.V. All rights reserved.