国产rhGH的免疫原性及其对临床疗效的影响

The Immunogenicity and Effect of Domestic Recombinant Human Growth Hormone: Serum GH-antibody Determination and Evaluation

目的 通过测定生长激素缺乏症 (GHD)患儿用国产重组人生长激素 (recom bined hum angrowth horm one,rh GH)治疗时血清生长激素抗体 (GH- Ab)水平及其结合特性 ,探讨 rh GH的免疫原性及其对疗效的影响。方法 对 6 1例 (男 49例 ,女 12例 ) GHD患儿用国产 rh GH治疗 ,每晚睡前皮下注射 rh GH 0 .1IU /kg共6个月 ;用放射免疫法测定治疗期间患儿血清 GH- Ab水平和滴度 ,并计算抗体结合容量、亲和常数 (Ka)。结果 48%患儿 (2 9/6 1)用药后 3个月血清 GH - Ab呈阳性至试验结束时仍未消失 ,其中 2 0例抗体为弱阳性 (结合率 <10 % ) ,9例呈强阳性 (结合率 >15 % ) ;5 2 %患儿 (32 /6 1)治疗期间抗体为阴性 ;血清 GH- Ab的结合容量、Ka及滴度均为低水平 ,分别为 (0 .1～ 4.8) pmol/L、(1.7× 10 7～ 6 .5× 10 8) L /mol和 1∶ 4～ 1∶ 8。GH- Ab阳性患儿治疗后的身高、身高增长速率及身高落后于正常 SD值的变化与同期阴性者比较无统计学差异 (P>0 .0 5 )。结论 本试验所用国产 rh GH对 GHD患儿身高增长具有确切的促进作用 ,其免疫原性所导致产生的 GH -

Objective To investigate the immunogenicity of a domestic recombinant human growth hormone (rhGH) preparation and assess its influence on the growth promoting effect. Methods We developed a specific and sensitive radioimmuno precipitation assay to determine the anti hGH antibody (GH Ab) in serum of GH deficient (GHD) children treated with rhGH preparation. The study included 61 GHD children (49 boys and 12 girls) who were treated with daily subcutaneous injections of rhGH (0.1IU/Kg) before sleep for six months. The patients' height, growth velocity and height standard deviation score were measured prior to and after treatment. The binding ratio with 125 I hGH and titer of GH Abs were measured by radioimmuno precipitation assay; the binding capacity and affinity (Ka) were analyzed by competitive RIA and Scatchard plot method. Results Three months after rhGH therapy, serum GH Abs were detected in 29 patients (48%), and their GH Abs were persistently positive till the end of the trial.Serum GH Ab was not detectable in the other 32 patients (52%) during treatment. The GH Abs positive samples, according to the 125 I hGH binding ratio (B/T%),were divided into the weakly positive (B/T<10%, n =20) and strong positive (B/T>15%, n =9) groups; their binding capacity, affinity (Ka) and titer were (0.1 4.8)pmol/L, (1.7×10 7 6.5×10 8)L/mol and 1∶4 1∶8, respectively. They were weak and not available to give negative effect to rhGH activity. The height and growth velocity as well as height standard deviation score of the GH Ab positive patients presented no decrease during treatment and were not significantly different from that of negative patients. Conclusion The domestic rhGH preparation certainly had growth promoting effect on the children with GHD. Nearly forty eight percent patients showed GH Ab positive in serum, but due to the lower titer and binding capacity, the GH Ab had no negative effect on the height velocity of GHD children.