HLA-DRB1等位基因与儿童特发性血小板减少性紫癜

目的：研究人类白细胞抗原（LA）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＜0．05，RR＝2．76，EF＝0．1064），而HLA－DRB1＊1202基因型显著降低（P＜0．025，RR＝0．20，PF＝0．7616）。（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＜0．025），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＊02（15／16）基因型显著相关（P分别为0．02和0．01），但难治性和非难治性ITP患儿间抗体阳性差异无显著性（P＞0．1）。结论：（1）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；（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＊02限制，但自身抗体阳性与否并不能预示ITP患儿的预后。

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

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.