人类白细胞抗原DRB1 等位基因与儿童特发性血小板减少性紫癜的相关性研究

目的研究人类白细胞抗原(human leukocyte antigen, HLA)DRB1等位基因与儿童特发性血小板减少性紫癜(idiopathic thrombocytopenic purpura, ITP)的关系.方法用聚合酶链反应-序列特异的寡核苷酸探针杂交技术对42例ITP患儿进行了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检测了其中36例ITP患儿血清中的抗GPⅡb/Ⅲa和抗GPIb/Ⅰx自身抗体.结果与健康对照相比,ITP患儿HLA-DRB1*17基因频率显著升高(P<0.05,RR＝2.76,EF=0.1064),而HLA-DRB1*1202基因频率显著降低(P<0.025,RR＝0.20,PF=0.7616);慢性难治性ITP患儿与非难治性患儿相比,HLA-DRB1*11基因频率显著升高(χ2＝6.091,P<0.025),且具有DRB1*11的患儿主要(5/6)为女性年长患儿;抗GPⅡb/Ⅲa及抗GPIb/Ⅰx自身抗体的阳性率都与HLA-DRB1*02(15/16)基因显著相关(P分别为0.02和0.01),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 DRB1*17可能与儿童ITP的易感性有关,而DRB1*1202则可能对儿童ITP的发病具有保护作用;具有DRB1*11基因的患儿易发展为慢性难治性ITP;血小板自身抗体与抗原表位的反应可能受DRB1*02限制,但自身抗体阳性与否并不能提示ITP患儿的预后.

Study on the relations between HLA-DRB1 alleles and idiopathic thrombocytopenic purpura in children

OBJECTIVE: To gain an insight into the relations between human leukocyte antigen-DRB1 (HLA-DRB1) alleles and idiopathic thrombocytopenic purpura (ITP) in children. METHODS: Polymerase chain reaction-sequence specific oligonucleotide (PCR-SSO) was used to identify DRB1 alleles of 42 children with ITP. Among them, 36 were identified for anti-GPIIb/IIIa and anti-GPIb/Ix autoantibody by modified monoclonal antibody specific immobilization of platelet antigens. RESULTS: Compared with health controls, the frequency of HLA-DRB1*17 significantly increased (P<0.05, relative risk=2.76, etiologic factor=0.1064) and the frequency of HLA-DRB1*1202 significantly decreased (P<0.025, relative risk=0.20, prophylactic factor=0.7616) in children with ITP. In comparison with patients of good response to steroids and IVIgG therapy, the frequency of HLA DRB1*11 significantly increased (Chi-square=6.091, P<0.025) in patients with a poor response, furthermore, the most of HLA-DRB1*11 positive patients were female teen-agers. Twenty-seven patients (75%) had anti GPIIb/IIIa and seventeen (47.22%) had anti_GPIb/Ix autoantibodies. The positivities of both anti_GP IIb/IIIa (P=0.02) and anti-GPIb/Ix (P=0.01) were associated with HLA-D RB1*02. However, the positivity of autoantibodies between refractory and non-refractory patients showed no significant difference. CONCLUSION: The allele of HLA-DRB1*17 seems to predict susceptibility of ITP in children, while HLA-DRB1*1202 appears to be protective to ITP. The allele of HLA DRB1*11 plays an important role in resistance to steroid and IgG therapy in children with ITP. It seems that the response to the antigenic epitope of GPIIb/IIIa and GPIb/Ix is restricted by HLA-DRB1*02, while the presence of the antibodies could not predict prognosis. In conclusion, the above preliminary findings indicate that genetic factors influence the clinical course of ITP, but the exact mechanism needs to be investigated further.