噬血细胞综合征诊断和治疗.ppt

噬血细胞综合征的诊断和治疗  定义 噬血细胞综合征( Haemophagocytic Syndrome/ Haemophagocytic Lymphohistiocytosis):由于细胞毒T细胞和NK细胞功能缺陷不能有效 清除病原,引起的以单核巨噬细胞和(或)淋巴细胞过度活化増殖,和 细胞因子风暴为病理免疫特征,主要表现为发热、脾大、全血细胞减少 、高甘油三酯、低纤维蛋白原、高血清铁蛋白,并可在骨髓、脾脏或淋 巴结活检中发现噬血现象的一组临床综合征。  Mutations in genes responsible for granule- dependent cytotoxic activity 分类 口 Primary/ Genetic HLH a Secondarv/Acquired HLH 口 Primarv/ Genetic HLH Gene Protein / HLH 9213-9g2 FHL-2 卫Us Perforin UNC13D Synexin recessive STXBP2(UNCIBB)Munc18-2 19p13.2-3 nme deficieney syndrom LyST l42』q22 RAB2A SHZDIA 325 X-linked XLP-2 IBIRCA P terrane immune defects saab as HPS-2, SCID, Irk deficency 口 Secondary/△ cquired HLH Autoinflammatory and autoimmune diseases (ma crophage activa tion syndrome) Malignant diseases Immune suppression, hematopoietie stem cell and Abbreviations CHS, Cnediak-Higashi syndrome: G52, Griscelli syndrome 2: xLP, x-linked lymphoproliferative syndrame: HPS.2, Hermansky-Pudlak syndrome 2: SCID, severe combined im munodeficiency: ITk, interleukin-2 inducible T-cEl kinase  发病机制 b uncontrolled and ineffec immune response in HLH Activation Activation Maturation Fallure to kill infected cells Docking Cytotoxic of cytotoxic lL-1IL-6 TNF-a Degranulation Tissue Infiltration Cytokine Storm Killing of target cell  发病机制 Highly activated yet ineffective multisystem inflammatory response/ Immunopathology HLH, related disorders Normal immune response Time  实验室检查 铁蛋白( Ferritin) Diseases Ferritin HLH 15830μg/mL ange,994-189721 autol mmune disease 1356g/mL ange,512-16367 viral diseas 1120μg/ range,535-6230 bacterial infections 972μg/mL range,523-7508 D10 000 ug/mL were 93% specific for the hlh diagnosis a 30000 are not uncommon in HLh and are 100% specific in the absence of an inborn error of iron metabolism  脾脏病理学:脾脏形态可见明确的噬血现象, EBV-EBER 见少量阳性,未见明确淋巴瘤改变