HLA-DRB1等位基因与儿童特发性血小板减少性紫癜

Relationship between HLA-DRB1 alleles and idiopathic thrombocytopenic purpura in children

目的 研究人类白细胞抗原 (HLA)DRB1等位基因与儿童特发性血小板减少性紫癜(ITP)的关系。方法 用PCR SSO法对 42例ITP患儿进行HLA DRB1等位基因分型 ,同时用改良的血小板抗原单抗特异性固相化法 (MAIPA)检测其中 36例ITP患儿血清中的抗GPⅡb/Ⅲa和GPⅠb/Ⅸ自身抗体。结果 ①与健康对照相比 ,ITP患儿HLA DRB1 17基因型显著升高 (P <0 .0 5 ,RR =2 .76 ,EF=0 .10 6 4) ,而HLA DRB1 12 0 2基因型显著降低 (P <0 .0 2 5 ,RR =0 .2 0 ,PF =0 .76 16 ) ;②慢性难治性ITP患儿与非难治性患儿相比 ,HLA DRB1 11基因型显著升高 (P <0 .0 2 5 ) ,且具有DRB1 11的患儿主要 (5 /6 )为女性年长患儿 ;③抗GPⅡb/Ⅲa及抗GPⅠb/Ⅸ自身抗体的阳性率都与HLA DRB1 0 2(15 /16 )基因型显著相关 (P分别为 0 .0 2和 0 .0 1) ,但难治性和非难治性ITP患儿间抗体阳性率差异无显著性 (P >0 .1)。结论 ①DRB1 17可能与儿童ITP的易感性有关 ,而DRB1 12 0 2则可能对儿童ITP的发病具有保护作用 ;②具有DRB1 11基因型的患儿易发展为慢性难治性ITP ;③血小板自身抗体与抗原表位的反应可能受DRB1 0 2限制 。

Objective To study the relationship between HLA-DRB1 alleles and idiopathic thrombocytopenic purpura (ITP) in children. Methods PCR-SSO was used to identify DRB1 alleles of 42 children with ITP. Among them, anti-GPⅡb/Ⅲa and anti-GPⅠb/Ⅸ autoantibody were detected in 36 cases by modified monoclonal antibody specific immobilization of platelet antigens (MAIPA). Results ① Compared with healthy controls, HLA-DRB1*17 was significantly increased (relative risk=2.76, P<0.05, etiologic factor=0.106*!4) and HLA-DRB1*1202 decreased (relative risk=0.20, P<0.025, prophylactic factor=0.761*!6) in children with ITP. ② In comparison with patients with good response to steroids and IgG therapy, HLA-DRB1*11 was significantly increased (P<0.025) in patients with a poor response, furthermore, most (5/6) of HLA-DRB1*11-positive patients were female teen-ager. ③ Twenty-seven patients (75%) had anti-GPⅡb/Ⅲa and seventeen (47.22%) had anti-GPⅠb/Ⅸ autoantibodies, the positivity rates of both anti-GPⅡb/Ⅲa (P=0.02) and anti-GPⅠb/Ⅸ (P=0.01) were associated with HLA-DRB1*02. However, the pos·/itivity rates of autoantibodies between refractory and non-refractory patients showed no significant difference. Conclusion ① The DRB1*17 seems to predict susceptibility to ITP in children, while DRB1*1202 appears to be protective to against ITP. ② The DRB1*11 plays an important role in resistance to steroid and IgG therapy in children with ITP. ③ It seems that the response to the antigenic epitope of GPⅡb/Ⅲa and GPⅠb/Ⅸ is restricted by DRB1*02, while the presence of the autoantibodies couldn’t predict prognosis. Our preliminary findings indicate that genetic factors influence the clinical course of ITP, but its exact mechanism needs to be further investigated.