双类似物鼻粘膜耐受对实验性自身免疫性重症肌无力的影响

Effects of nasal tolerance with dual analogue on experimental autoimmune myasthenia gravis in Lewis rats

目的 在实验性自身免疫性重症肌无力 (EAMG)动物模型采用双类似物进行鼻粘膜免疫耐受 ,观察其临床及免疫功能变化 ,评价疗效并探讨其作用机制。方法 建立Lewis大鼠EAMG动物模型 ,选取经预实验证实有效的最低剂量为治疗量 ,检测致敏同时 (A组 )和缓解期第 1天 (B组 )给予双类似物鼻粘膜免疫耐受治疗后 ,大鼠体重、临床症状、致敏第 35天血清抗AChR抗体IgG含量及其淋巴细胞在不同刺激原作用下的增殖情况。结果 (1 )治疗后EAMG大鼠体重增加 ,临床症状缓解。 (2 )治疗后血清抗AChR抗体IgG含量 (吸光度 ,A值 ) :A组 (0 98± 0 2 4 )和B组 (0 95± 0 2 6)均少于各自对照组 (分别为 1 1 8± 0 1 0和 1 1 9± 0 1 2 ) ,但A、B组间差异无显著意义。 (3)针对AChR等特异性抗原的淋巴细胞增殖指数 :A组 (1 71± 0 78)和B组 (1 97± 0 56)与对照组 (3 2 4± 1 31和 3 1 9±1 50 )相比均减低 ,增殖反应明显受抑制。结论 双类似物鼻粘膜耐受能明显缓解EAMG的肌无力症状 ,并伴有特异性T。

Objective To study the effect of nasal tolerance with a dual analogue (Lys262 Ala207) on experimental autoimmune myasthenia gravis (EAMG) and the underlying mechanisms, the clinical and immunological changes were observed in Lewis rats treated with dual analogue Methods Different doses of dual analogues were given to Lewis rats immunized with acetylcholine receptor (AChR) in complete Freud's adjuvant (CFA) and the medium dosage was chosen in the following studies As comparing the effects of treatment of the predetermined dosage of dual analogue at different time points, the body weight and clinical symptoms of Lewis rats immunized with AChR in CFA were evaluated The levels of anti AChR IgG in serum were tested by ELISA Proliferative responses of lymphocytes to no antigen, AChR, dual analogue, control MBP peptide, MBP, or Con A were tested Results Lewis rats receiving dual analogue nasally for 10 consecutive days at the time of immunization (Group A) or the first day after complete remission from the acute phase of the disease (Group B) sparsely developed EAMG with reduced severity than the corresponding control groups The subsiding disease was associated with decreased amount of anti AChR IgG in serum expressed as optic density ( A ) at 405 nm On day 35 post immunization, the A values in group B vs control group were 0 95±0 26 and 1 19±0 12, respectively Proliferative responses expressed as stimulation index (SI) were suppressed in response to antigen specific stimulations in rats receiving dual analogue as compared with rats receiving control peptide For instance, the values of SI in response to AChR in group A and control group were 1 71±0 78 and 3 24±1 31, respectively Those values were suppressed to a less extent in group B vs control group (1 97±0 56 vs 3 19± 1 50) Conclusions Nasal administration of a dual analogue Lys262 Ala207, at two different time points post immunization should ameliorate muscular weakness in EAMG rats involved in decreased levels of anti AChR antibodies and antigen specific T cell proliferation