1、2023/1/30特发性血小板减少性紫癜（Idiopathic Thrombocytopenic Idiopathic Thrombocytopenic Purpura,ITPPurpura,ITP）发病机制发病机制2023/1/30发病机制发病机制体液免疫体液免疫 1体液免疫因素体液免疫因素 自身抗体识别的靶抗原几乎涉及血小板膜表面所有自身抗体识别的靶抗原几乎涉及血小板膜表面所有分子分子(抗血小板糖蛋白抗血小板糖蛋白IIb/IIIa、Ib/IX、Ia/IIa、IV、VI和和P-SelP-Sel等等)。结合自身抗体的血小板易被网状内皮系统破坏结合自身抗体的血小板易被网状内皮系统破坏 自身抗体引
2、起获得性血小板功能异常自身抗体引起获得性血小板功能异常 自身抗体结合巨核细胞，干扰巨核细胞分化成熟自身抗体结合巨核细胞，干扰巨核细胞分化成熟 McMillan等发现，等发现，2/3 ITP患者血浆能明显抑制巨核患者血浆能明显抑制巨核细胞生成（细胞生成（2595%）,巨核细胞数量和成熟度均受巨核细胞数量和成熟度均受到抑制。到抑制。Chang等也证实自身抗体明显抑制脐血来源等也证实自身抗体明显抑制脐血来源巨核细胞生长巨核细胞生长 Blood 2004;103:1364-1369Blood 2004;103:1364-1369 Blood 2003;102:887-895 Blood 2003;10
3、2:887-8952023/1/30发病机制发病机制体液免疫体液免疫1、血小板相关抗体（、血小板相关抗体（platelet-associated immuoglobulin PAIgG）Harrington 等等1951年证实：年证实：27例例ITP患患者的血浆输给正常志愿者，者的血浆输给正常志愿者，16例例PC减少减少 PC CD8+T cells.Trend toward Th1 activation.primarily react with GPIIb/IIIa.Adherent cell(APC)dependent.2023/1/30Approximately 40%of patien
4、ts with chronic AITP have no detectible antibodies on their platelets or in their plasma.Why?How are their platelets being destroyed?2023/1/30TumorcellCTL2023/1/30Anderson et al.Nature Medicine 2003 CD8 cellPlateletLysis(kill)Suggests that a novel therapeutic targeting cell mediated immunity may ben
5、efit some ITP patients.2023/1/30Disturbed apoptosis of T-cells in patients with active idiopathic thrombocytopenic purpura apoptotic resistance of activated T-lymphocytes in patients with active ITP may lead to defective clearance of autoreactive T-lymphocytes through AICD（activation induced cell death),which might cause a continued immune destruction of plateletsOlsson B,et al.Thromb Haemost.20052023/1/30发病机制发病机制3、雌激素、雌激素4、遗传因素、遗传因素 HLA DRW9 和和HLA DQW3
